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Development of the Urogenital System

The urogenital system is derived from intermediate mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation. The intermediate mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation differentiates into nephrogenic cords (which will go on to form the urinary system) and an adjacent area known as the gonadal ridge (which will go on to form the gonads Gonads The gamete-producing glands, ovary or testis. Hormones: Overview and Types). The nephrogenic cords elongate in a caudal direction and sequentially develop 3 different structures: the pronephros (rudimentary and nonfunctional), the mesonephros (forms the primitive urinary system), and the metanephros (forms the permanent kidney). Concurrently, the genital system develops in close association with the urinary system. Genital development depends on chromosomal sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria, which determines whether the primitive gonads Gonads The gamete-producing glands, ovary or testis. Hormones: Overview and Types differentiate into testes Testes Gonadal Hormones or ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries: Anatomy. The gonads Gonads The gamete-producing glands, ovary or testis. Hormones: Overview and Types then secrete certain hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types, which direct further development of both the internal and external genital structures.

Last updated: 5 Aug, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Early Embryonic Development

Bilaminar disc Bilaminar disc Embryoblast and Trophoblast Development

Develops around week 2 of embryonic life: 

Trilaminar disc Trilaminar disc Gastrulation and Neurulation

Layers:

Layers of the trilaminar disc

Layers of the trilaminar disc Trilaminar disc Gastrulation and Neurulation

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Folding

  • The trilaminar disc Trilaminar disc Gastrulation and Neurulation folds in 2 directions:
    • Lateral folding creates a “cylindrical” structure surrounded by ectoderm Ectoderm The outer of the three germ layers of an embryo. Gastrulation and Neurulation.
    • Cranial-to-caudal folding
  • Key structures for urogenital development at this stage:
    • Intermediate mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation → develops into:
      • Nephrogenic cords → goes on to form the urinary system
      • Gonadal ridge (area adjacent to the nephrogenic cords) → goes on to form the stromal tissue of the gonads Gonads The gamete-producing glands, ovary or testis. Hormones: Overview and Types
    • Primordial germ cells Primordial germ cells Gametogenesis:
      • Originate from epiblast Epiblast Embryoblast and Trophoblast Development cells
      • Cells migrate to the yolk sac Yolk Sac The first of four extra-embryonic membranes to form during embryogenesis. In reptiles and birds, it arises from endoderm and mesoderm to incorporate the egg yolk into the digestive tract for nourishing the embryo. In placental mammals, its nutritional function is vestigial; however, it is the source of intestinal mucosa; blood cells; and germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. Embryoblast and Trophoblast Development
      • Will eventually migrate along the allantois Allantois An extra-embryonic membranous sac derived from the yolk sac of reptiles; birds; and mammals. It lies between two other extra-embryonic membranes, the amnion and the chorion. The allantois serves to store urinary wastes and mediate exchange of gas and nutrients for the developing embryo. Development of the Abdominal Organs to the gonadal ridge
      • Go on to become the spermatozoa or oocytes Oocytes Female germ cells derived from oogonia and termed oocytes when they enter meiosis. The primary oocytes begin meiosis but are arrested at the diplotene state until ovulation at puberty to give rise to haploid secondary oocytes or ova (ovum). Ovaries: Anatomy
Cross-sectional view of the early embryo

Cross-sectional view of the early embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week

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Development of the Urinary System

The kidney develops from embryonic mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation in 3 successive forms from the nephrogenic cords as the cords elongate in a cranial-to-caudal direction.

Note: This animation does not have sound.

Pronephros

  • Appears in week 4 as a cluster of a tubule and a few cells (nephrotomes) 
  • Develops in nephrogenic cords in the cervical region Cervical region Spinal Cord: Anatomy 
  • Rudimentary and nonfunctional 
  • Degenerates by the end of week 4 (persists < 1 week)
  • Purpose unclear, though may be a “scaffold” off which the next structure (the mesonephros) develops
Developmental location of the pronephros, mesonephros, and metanephros in the developing embryo

Developmental location of the pronephros, mesonephros, and metanephros in the developing embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week

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Mesonephros

  • Begins to develop as pronephros regresses around week 5
  • Most of the mesonephros regresses by week 10.
  • Develops lower, in the thoracolumbar region
  • Connects with the cloaca Cloaca A dilated cavity extended caudally from the hindgut. In adult birds, reptiles, amphibians, and many fishes but few mammals, cloaca is a common chamber into which the digestive, urinary and reproductive tracts discharge their contents. In most mammals, cloaca gives rise to large intestine; urinary bladder; and genitalia. Development of the Abdominal Organs at the caudal end of the primitive gut tube
  • Consists of:
    • A longitudinal mesonephric duct Mesonephric duct A pair of excretory ducts of the middle kidneys of an embryo, also called mesonephric ducts. In higher vertebrates, wolffian ducts persist in the male forming vas deferens, but atrophy into vestigial structures in the female. Kidneys: Anatomy (also called the wolffian duct Wolffian duct A pair of excretory ducts of the middle kidneys of an embryo, also called mesonephric ducts. In higher vertebrates, wolffian ducts persist in the male forming vas deferens, but atrophy into vestigial structures in the female. Kidneys: Anatomy)
    • A series of tubules coming off that main duct, growing anteriorly toward the aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy 
  • Small glomerular vessels grow posteriorly off the aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy toward the mesonephric tubules, forming primitive renal corpuscles:
    • Mesonephric tubules grow around the glomerular capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology, forming Bowman capsules (though these will ultimately regress).
    • Forms the primitive urinary system
  • Filtration of blood begins: 
    • Blood flows down the aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy → glomerular capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology
    • Filtered through Bowman capsule Capsule An envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides. Bacteroides 
    • Filtrate travels down the mesonephric tubule → mesonephric duct Mesonephric duct A pair of excretory ducts of the middle kidneys of an embryo, also called mesonephric ducts. In higher vertebrates, wolffian ducts persist in the male forming vas deferens, but atrophy into vestigial structures in the female. Kidneys: Anatomy cloaca Cloaca A dilated cavity extended caudally from the hindgut. In adult birds, reptiles, amphibians, and many fishes but few mammals, cloaca is a common chamber into which the digestive, urinary and reproductive tracts discharge their contents. In most mammals, cloaca gives rise to large intestine; urinary bladder; and genitalia. Development of the Abdominal Organs allantois Allantois An extra-embryonic membranous sac derived from the yolk sac of reptiles; birds; and mammals. It lies between two other extra-embryonic membranes, the amnion and the chorion. The allantois serves to store urinary wastes and mediate exchange of gas and nutrients for the developing embryo. Development of the Abdominal Organs
  • Mesonephros is present only from weeks 5–10 (at which time the permanent kidney formed from the metanephros takes over).
  • The mesonephric ducts persist in males and form part of the male reproductive system.
Graphical summary of the mesonephros

Graphical summary of the mesonephros:
Note that the nephrogenic cords (primary nephric ducts) elongate and join with the cloaca Cloaca A dilated cavity extended caudally from the hindgut. In adult birds, reptiles, amphibians, and many fishes but few mammals, cloaca is a common chamber into which the digestive, urinary and reproductive tracts discharge their contents. In most mammals, cloaca gives rise to large intestine; urinary bladder; and genitalia. Development of the Abdominal Organs. Mesonephric tubules grow in a stepladder-like pattern and function as a primitive urinary system, while the definitive kidney develops from the metanephros further down in the growing pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 “hip” bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis: Anatomy.

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Metanephros

The permanent kidney is formed from the metanephros.

  • Develops starting around the 5th week
  • Cells in the intermediate mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation in the pelvic region begin to differentiate into a structure called the metanephric blastema Metanephric blastema Wilms Tumor, which:
    • Ultimately becomes the cells making up the nephrons
    • Releases growth factors that stimulate the development of an outpouching off the caudal portion of the mesonephric duct Mesonephric duct A pair of excretory ducts of the middle kidneys of an embryo, also called mesonephric ducts. In higher vertebrates, wolffian ducts persist in the male forming vas deferens, but atrophy into vestigial structures in the female. Kidneys: Anatomy called the ureteric buds
  • Ureteric buds grow toward and invade the metanephric blastema Metanephric blastema Wilms Tumor:
    • Elongating stalk of the ureteric bud develops into the ureter.
    • Within the metanephric blastema Metanephric blastema Wilms Tumor, the ureteric buds undergo a series of branchings to form the:
      • Renal pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 “hip” bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis: Anatomy
      • Major calyces Major calyces Recesses of the kidney pelvis which divides into two wide, cup-shaped major renal calices, with each major calyx subdivided into 7 to 14 minor calices. Urine empties into a minor calyx from collecting tubules, then passes through the major calyx, renal pelvis, and ureter to enter the urinary bladder. Kidneys: Anatomy
      • Minor calyces Minor calyces Recesses of the kidney pelvis which divides into two wide, cup-shaped major renal calices, with each major calyx subdivided into 7 to 14 minor calices. Urine empties into a minor calyx from collecting tubules, then passes through the major calyx, renal pelvis, and ureter to enter the urinary bladder. Kidneys: Anatomy
      • Collecting tubules Collecting tubules Straight tubes commencing in the radiate part of the kidney cortex where they receive the curved ends of the distal convoluted tubules. In the medulla the collecting tubules of each pyramid converge to join a central tube (duct of Bellini) which opens on the summit of the papilla. Kidneys: Anatomy
  • Metanephric mesodermal cap: 
    • Mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation from the metanephric blastema Metanephric blastema Wilms Tumor sitting “on top of” the developing collecting ducts
    • Elongates, forming the tubular system The tubular system The kidneys regulate water and solute homeostasis through the processes of filtration, reabsorption, secretion, and excretion. After the filtration of blood through the glomeruli, the tubular system takes over and is responsible for adjusting the urine composition throughout the remainder of the nephron. Tubular System of the nephrons → becomes known as the metanephric tubule
    • The metanephric tubule fuses with the collecting tubule, creating 1 continuous system.
  • Bowman capsule Capsule An envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides. Bacteroides: forms off the growing end of the metanephric tubule
  • Glomerular capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology:
    • Develop off the common iliac arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology
    • Become associated with Bowman capsule Capsule An envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides. Bacteroides at the end of the metanephric tubules → begin creating “urine” (Note: True waste products from the fetus are removed via the placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity.)
  • Nephrons are formed until birth.
  • Nephron Nephron The functional units of the kidney, consisting of the glomerulus and the attached tubule. Kidneys: Anatomy maturation continues after birth.

Position of the kidney and changes in vascularization

  • The kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy are initially located in the pelvic region.
  • As the caudal portion of the body grows downward, the relative location of the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy “ascends” into the upper quadrants of the abdomen (failure to ascend results in a pelvic kidney).
  • As the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy ascend, the original blood supply degenerates.
  • New vessels (higher up) develop off the aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy and invade the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy, becoming the mature renal arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology.
  • If the original vessels fail to regress, they may persist as additional renal arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology or veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology.
Ascent of the kidneys and corresponding change in vascular supply

Ascent of the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy and corresponding change in vascular supply

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Development of the bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess and urethra Urethra A tube that transports urine from the urinary bladder to the outside of the body in both the sexes. It also has a reproductive function in the male by providing a passage for sperm. Urinary Tract: Anatomy

Between the 4th and 7th weeks of development, the cloaca Cloaca A dilated cavity extended caudally from the hindgut. In adult birds, reptiles, amphibians, and many fishes but few mammals, cloaca is a common chamber into which the digestive, urinary and reproductive tracts discharge their contents. In most mammals, cloaca gives rise to large intestine; urinary bladder; and genitalia. Development of the Abdominal Organs divides into:

  • Urogenital sinus Urogenital Sinus Congenital Malformations of the Female Reproductive System:
    • From the anterior portion of the cloaca Cloaca A dilated cavity extended caudally from the hindgut. In adult birds, reptiles, amphibians, and many fishes but few mammals, cloaca is a common chamber into which the digestive, urinary and reproductive tracts discharge their contents. In most mammals, cloaca gives rise to large intestine; urinary bladder; and genitalia. Development of the Abdominal Organs
    • Connects to the ureters Ureters One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the urinary bladder. Urinary Tract: Anatomy and mesonephric ducts
    • The urogenital sinus Urogenital Sinus Congenital Malformations of the Female Reproductive System has 3 portions:
      • Proximal (largest) → urinary bladder Urinary Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters (ureter), and is held there until urination. Urinary Tract: Anatomy 
      • Middle (narrow) → origin of prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. and prostatic and membranous urethra Membranous urethra Urinary Tract: Anatomy in males and the entire urethra Urethra A tube that transports urine from the urinary bladder to the outside of the body in both the sexes. It also has a reproductive function in the male by providing a passage for sperm. Urinary Tract: Anatomy in females
      • Distal → penile urethra Penile urethra Urinary Tract: Anatomy in males
  • Anal canal:
    • From the posterior portion of the cloaca Cloaca A dilated cavity extended caudally from the hindgut. In adult birds, reptiles, amphibians, and many fishes but few mammals, cloaca is a common chamber into which the digestive, urinary and reproductive tracts discharge their contents. In most mammals, cloaca gives rise to large intestine; urinary bladder; and genitalia. Development of the Abdominal Organs
    • Connects to the developing hindgut Hindgut Development of the Abdominal Organs
  • Urorectal septum Urorectal septum Development of the Abdominal Organs
    • Separates the urogenital sinus Urogenital Sinus Congenital Malformations of the Female Reproductive System from the anal canal 
    • Starts at the superior/proximal portion of the cloaca Cloaca A dilated cavity extended caudally from the hindgut. In adult birds, reptiles, amphibians, and many fishes but few mammals, cloaca is a common chamber into which the digestive, urinary and reproductive tracts discharge their contents. In most mammals, cloaca gives rise to large intestine; urinary bladder; and genitalia. Development of the Abdominal Organs → grows distally until it reaches the outside of the body, where it becomes the perineal body
    • Failure of the septum to form correctly can result in fistulas between the urogenital system and the anorectum.
  • The allantois Allantois An extra-embryonic membranous sac derived from the yolk sac of reptiles; birds; and mammals. It lies between two other extra-embryonic membranes, the amnion and the chorion. The allantois serves to store urinary wastes and mediate exchange of gas and nutrients for the developing embryo. Development of the Abdominal Organs (drains the cloaca Cloaca A dilated cavity extended caudally from the hindgut. In adult birds, reptiles, amphibians, and many fishes but few mammals, cloaca is a common chamber into which the digestive, urinary and reproductive tracts discharge their contents. In most mammals, cloaca gives rise to large intestine; urinary bladder; and genitalia. Development of the Abdominal Organs through the umbilical cord Umbilical cord The flexible rope-like structure that connects a developing fetus to the placenta in mammals. The cord contains blood vessels which carry oxygen and nutrients from the mother to the fetus and waste products away from the fetus. Placenta, Umbilical Cord, and Amniotic Cavity) → ultimately turns into the median umbilical ligament

Early Embryologic Development of the Genital System

Overview of typical sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria development

  • Chromosomal sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria → determines gonadal sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria → determines phenotypic sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria
  • Up until 6 weeks of gestation, sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria development is identical and nonbinary; developing structures include:
  • The genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure present at fertilization Fertilization To undergo fertilization, the sperm enters the uterus, travels towards the ampulla of the fallopian tube, and encounters the oocyte. The zona pellucida (the outer layer of the oocyte) deteriorates along with the zygote, which travels towards the uterus and eventually forms a blastocyst, allowing for implantation to occur. Fertilization and First Week will determine how the developing bipotent gonads Gonads The gamete-producing glands, ovary or testis. Hormones: Overview and Types differentiate (e.g., into a testis or an ovary).
  • The developing gonads Gonads The gamete-producing glands, ovary or testis. Hormones: Overview and Types will then secrete hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types.
    • The presence and/or absence of specific hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types will determine how the remaining structures differentiate.
    • In general, female organs and structures are the “default” phenotype Phenotype The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics if specific genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure and hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types are not present to stimulate male differentiation.
Sex differentiation

Sex differentiation Sex differentiation The process in developing sex- or gender-specific tissue, organ, or function after sex determination processes have set the sex of the gonads. Major areas of sex differentiation occur in the reproductive tract (genitalia) and the brain. Sex Determination from the mesonephric (wolffian) and paramesonephric (müllerian) ducts:
In females, the mesonephric ducts regress while the paramesonephric ducts persist. The paramesonephric ducts remain open to the intraembryonic coelom (the eventual peritoneal cavity Peritoneal Cavity The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of winslow, or epiploic foramen. Peritoneum: Anatomy) near the gonads Gonads The gamete-producing glands, ovary or testis. Hormones: Overview and Types, and the inferior/medial ends fuse into a common body in the midline, forming the uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy and upper vagina Vagina The vagina is the female genital canal, extending from the vulva externally to the cervix uteri internally. The structures have sexual, reproductive, and urinary functions and a rich blood supply, mainly arising from the internal iliac artery. Vagina, Vulva, and Pelvic Floor: Anatomy.
In males, the mesonephric ducts are closely associated with the gonads Gonads The gamete-producing glands, ovary or testis. Hormones: Overview and Types; they enter the urogenital sinus Urogenital Sinus Congenital Malformations of the Female Reproductive System separately on each side becoming parts of the ejaculatory system, while the urogenital sinus Urogenital Sinus Congenital Malformations of the Female Reproductive System becomes the bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess and prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. .

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Embryologic development of the bipotent gonads Gonads The gamete-producing glands, ovary or testis. Hormones: Overview and Types

  • A portion of the intermediate mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation covering the anterior portion of the nephrogenic cords → known as the gonadal ridge
  • Epithelial cells in the gonadal ridge:
    • Proliferate and condense
    • Penetrate into the mesenchyme to form the primitive sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria cords (still indifferent gonads Gonads The gamete-producing glands, ovary or testis. Hormones: Overview and Types)
    • These cells will become the stromal cells:
      • Sertoli and Leydig cells Leydig Cells Steroid-producing cells in the interstitial tissue of the testis. They are under the regulation of pituitary hormones; luteinizing hormone; or interstitial cell-stimulating hormone. Testosterone is the major androgen (androgens) produced. Testicles: Anatomy in males
      • Granulosa and theca cells Theca cells The flattened stroma cells forming a sheath or theca outside the basal lamina lining the mature ovarian follicle. Thecal interstitial or stromal cells are steroidogenic, and produce primarily androgens which serve as precursors of estrogens in the granulosa cells. Puberty in females
  • Primordial germ cells Primordial germ cells Gametogenesis:
    • Will differentiate into spermatozoa or oocytes Oocytes Female germ cells derived from oogonia and termed oocytes when they enter meiosis. The primary oocytes begin meiosis but are arrested at the diplotene state until ovulation at puberty to give rise to haploid secondary oocytes or ova (ovum). Ovaries: Anatomy
    • Originate in the epiblast Epiblast Embryoblast and Trophoblast Development
    • Migrate to the yolk sac Yolk Sac The first of four extra-embryonic membranes to form during embryogenesis. In reptiles and birds, it arises from endoderm and mesoderm to incorporate the egg yolk into the digestive tract for nourishing the embryo. In placental mammals, its nutritional function is vestigial; however, it is the source of intestinal mucosa; blood cells; and germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. Embryoblast and Trophoblast Development → through the allantois Allantois An extra-embryonic membranous sac derived from the yolk sac of reptiles; birds; and mammals. It lies between two other extra-embryonic membranes, the amnion and the chorion. The allantois serves to store urinary wastes and mediate exchange of gas and nutrients for the developing embryo. Development of the Abdominal Organs ( umbilical cord Umbilical cord The flexible rope-like structure that connects a developing fetus to the placenta in mammals. The cord contains blood vessels which carry oxygen and nutrients from the mother to the fetus and waste products away from the fetus. Placenta, Umbilical Cord, and Amniotic Cavity) → along the dorsal mesentery Mesentery A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. Peritoneum: Anatomy of the hindgut Hindgut Development of the Abdominal Organs → genital ridges
    • Germ cells Germ Cells The reproductive cells in multicellular organisms at various stages during gametogenesis. Gametogenesis invade the gonadal ridges by approximately 6 weeks
  • Developing sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria cords associate with migrating primordial germ cells Primordial germ cells Gametogenesis to form gonads Gonads The gamete-producing glands, ovary or testis. Hormones: Overview and Types.

Development of the Internal Male Genitalia

Overview of the adult male genital structures

Structures of the male reproductive system

Structures of the male reproductive system

Image: “Male Reproductive System” by OpenStax College. License: CC BY 4.0, cropped by Lecturio.

Development of the testes Testes Gonadal Hormones

Note: This animation does not have sound.
  • Male development starts as a result of the presence of the sex-determining region of the Y chromosome Y chromosome The male sex chromosome, being the differential sex chromosome carried by half the male gametes and none of the female gametes in humans and in some other male-heterogametic species in which the homologue of the X chromosome has been retained. Basic Terms of Genetics gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics (SRY gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics):
    • Produces SRY protein (also known as testis-determining factor [TDF]) 
    • SRY/TDF stimulates the differentiation of the bipotent gonad into testes Testes Gonadal Hormones by stimulating stromal cells to differentiate into:
      • Leydig cells Leydig Cells Steroid-producing cells in the interstitial tissue of the testis. They are under the regulation of pituitary hormones; luteinizing hormone; or interstitial cell-stimulating hormone. Testosterone is the major androgen (androgens) produced. Testicles: Anatomy → secrete testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens
      • Sertoli cells Sertoli Cells Supporting cells projecting inward from the basement membrane of seminiferous tubules. They surround and nourish the developing male germ cells and secrete androgen-binding protein and hormones such as anti-mullerian hormone. The tight junctions of sertoli cells with the spermatogonia and spermatocytes provide a blood-testis barrier. Testicles: Anatomy → secrete müllerian inhibitory factor (MIF) (also called antimüllerian hormone ( AMH AMH A glycoprotein that causes regression of mullerian ducts. It is produced by sertoli cells of the testes. In the absence of this hormone, the mullerian ducts develop into structures of the female reproductive tract. In males, defects of this hormone result in persistent mullerian duct, a form of male pseudohermaphroditism. Primary Amenorrhea))
      • Seminiferous tubules Seminiferous Tubules The convoluted tubules in the testis where sperm are produced (spermatogenesis) and conveyed to the rete testis. Spermatogenic tubules are composed of developing germ cells and the supporting sertoli cells. Testicles: Anatomy
  • Testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens:
    • Stimulates differentiation of the wolffian/mesonephric ducts into:
      • Epididymis Epididymis The convoluted cordlike structure attached to the posterior of the testis. Epididymis consists of the head (caput), the body (corpus), and the tail (cauda). A network of ducts leaving the testis joins into a common epididymal tubule proper which provides the transport, storage, and maturation of spermatozoa. Testicles: Anatomy
      • Vas deferens Vas Deferens The excretory duct of the testes that carries spermatozoa. It rises from the scrotum and joins the seminal vesicles to form the ejaculatory duct. Testicles: Anatomy
      • Seminal vesicles Seminal vesicles A saclike, glandular diverticulum on each ductus deferens in male vertebrates. It is united with the excretory duct and serves for temporary storage of semen.
      • Ejaculatory ducts Ejaculatory Ducts Paired ducts in the human male through which semen is ejaculated into the urethra.
    • Is converted to dihydrotestosterone Dihydrotestosterone A potent androgenic metabolite of testosterone. It is produced by the action of the enzyme 3-oxo-5-alpha-steroid 4-dehydrogenase. Gonadal Hormones ( DHT DHT A potent androgenic metabolite of testosterone. It is produced by the action of the enzyme 3-oxo-5-alpha-steroid 4-dehydrogenase. Gonadal Hormones) by 5α-reductase → stimulates development of:
  • MIF → causes regression Regression Corneal Abrasions, Erosion, and Ulcers of the müllerian/paramesonephric ducts (which develop into internal female structures)
  • Primordial germ cells Primordial germ cells Gametogenesis differentiate into sperm.
  • The process of differentiation is largely completed by 12 weeks of gestation.

Development of the Internal Female Genitalia

Development of the ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries: Anatomy

  • Development of the ovary from the bipotent gonad requires:
    • Absence of the SRY gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics (preventing differentiation into testes Testes Gonadal Hormones)
      • No testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens → no development of the mesonephric ducts
      • No MIF → paramesonephric/müllerian ducts persist 
    • Presence of several genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure found on chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 1
    • Begins around 10 weeks of development
  • Epithelial cells from the gonadal ridge → become follicular cells:
    • Cell types:
      • Granulosa cells 
      • Theca cells Theca cells The flattened stroma cells forming a sheath or theca outside the basal lamina lining the mature ovarian follicle. Thecal interstitial or stromal cells are steroidogenic, and produce primarily androgens which serve as precursors of estrogens in the granulosa cells. Puberty
    • Produce estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy → stimulate the formation of the external female genitalia
  • Primordial germ cells Primordial germ cells Gametogenesis:
    • Develop into oocytes Oocytes Female germ cells derived from oogonia and termed oocytes when they enter meiosis. The primary oocytes begin meiosis but are arrested at the diplotene state until ovulation at puberty to give rise to haploid secondary oocytes or ova (ovum). Ovaries: Anatomy
    • Associate with the follicular cells

Development of the fallopian tubes Fallopian tubes The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The fallopian tubes receive an ovum after ovulation and help move it and/or a fertilized embryo toward the uterus via ciliated cells lining the tubes and peristaltic movements of its smooth muscle. Uterus, Cervix, and Fallopian Tubes: Anatomy, uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy, and vagina Vagina The vagina is the female genital canal, extending from the vulva externally to the cervix uteri internally. The structures have sexual, reproductive, and urinary functions and a rich blood supply, mainly arising from the internal iliac artery. Vagina, Vulva, and Pelvic Floor: Anatomy

Step 1: Fusion of the paramesonephric ducts

  • The ducts fuse in the midline adjacent to the urogenital sinus Urogenital Sinus Congenital Malformations of the Female Reproductive System.
  • Fused paramesonephric ducts differentiate into:
    • Uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy
    • Cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy
    • Upper vagina Vagina The vagina is the female genital canal, extending from the vulva externally to the cervix uteri internally. The structures have sexual, reproductive, and urinary functions and a rich blood supply, mainly arising from the internal iliac artery. Vagina, Vulva, and Pelvic Floor: Anatomy
  • The medial walls of the ducts initially form a longitudinal midline septum.
    • This septum normally fully regresses, creating a single cavity.
    • The septum can persist, resulting in a longitudinal uterine, cervical, and/or vaginal septum.
  • The lateral ends of the paramesonephric ducts remain “unfused” → these will differentiate into the fallopian tubes Fallopian tubes The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The fallopian tubes receive an ovum after ovulation and help move it and/or a fertilized embryo toward the uterus via ciliated cells lining the tubes and peristaltic movements of its smooth muscle. Uterus, Cervix, and Fallopian Tubes: Anatomy

Step 2: Connection of the fused paramesonephric ducts to the urogenital sinus Urogenital Sinus Congenital Malformations of the Female Reproductive System

Development of External Genitalia

  • Up until 6 weeks of gestation, sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria development is identical and nonbinary.
  • Early structures develop from folds in the cloaca Cloaca A dilated cavity extended caudally from the hindgut. In adult birds, reptiles, amphibians, and many fishes but few mammals, cloaca is a common chamber into which the digestive, urinary and reproductive tracts discharge their contents. In most mammals, cloaca gives rise to large intestine; urinary bladder; and genitalia. Development of the Abdominal Organs and include:
    • Genital tubercle 
    • Genital folds
    • Genital swellings
  • Development of the external genitalia depends on the hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types present:
    • Testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens/ DHT DHT A potent androgenic metabolite of testosterone. It is produced by the action of the enzyme 3-oxo-5-alpha-steroid 4-dehydrogenase. Gonadal Hormones → male structures
    • Estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy → female structures
Table: Development of the external genitalia from early structures
Undifferentiated structure In the presence of testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens Estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy/lack of testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens
Urogenital sinus Urogenital Sinus Congenital Malformations of the Female Reproductive System
  • Prostatic urethra Prostatic urethra
  • Membranous urethra Membranous urethra Urinary Tract: Anatomy
  • Prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. gland
  • Bulbourethral glands Bulbourethral Glands Glands situated on each side of the prostate that secrete a fluid component of the seminal fluid into the urethra.
  • ( Bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess*)
Genital tubercle (forms erectile tissue)
  • Glans penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis: Anatomy
  • Corpus cavernosum
  • Corpus spongiosum Corpus spongiosum Penis: Anatomy
Genital folds
  • Shaft of the penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis: Anatomy
  • Penile urethra Penile urethra Urinary Tract: Anatomy
Labia minora Labia minora Vagina, Vulva, and Pelvic Floor: Anatomy
Genital swelling Swelling Inflammation Scrotum Scrotum A cutaneous pouch of skin containing the testicles and spermatic cords. Testicles: Anatomy Labia majora Labia majora Vagina, Vulva, and Pelvic Floor: Anatomy
*Development is independent of hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types.
Phenotypic differentiation of the external genitalia in male and female embryos

Phenotypic differentiation of the external genitalia in male and female embryos:
Both male and female external genitalia develop from the same starting structures but diverge as they are exposed to different levels of androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens and estrogens.

Image by Lecturio. License: CC BY-NC-SA 4.0

Clinical Relevance

Disorders of urinary development

  • Horseshoe kidney Horseshoe Kidney Congenital Renal Abnormalities: developmental defect of the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy in which the inferior poles are fused together. As the kidney attempts to migrate superiorly during development, it is blocked by the superior mesenteric artery Superior mesenteric artery A large vessel supplying the whole length of the small intestine except the superior part of the duodenum. It also supplies the cecum and the ascending part of the colon and about half the transverse part of the colon. It arises from the anterior surface of the aorta below the celiac artery at the level of the first lumbar vertebra. Small Intestine: Anatomy. The vascular supplies and collecting system of the kidney also tend to have various degrees of distortion Distortion Defense Mechanisms. Individuals are typically asymptomatic, with incidental diagnosis made on imaging. Other presentations include infection, obstruction, hydronephrosis Hydronephrosis Hydronephrosis is dilation of the renal collecting system as a result of the obstruction of urine outflow. Hydronephrosis can be unilateral or bilateral. Nephrolithiasis is the most common cause of hydronephrosis in young adults, while prostatic hyperplasia and neoplasm are seen in older patients. Hydronephrosis, and calculi. 
  • Duplications of the collecting system: known as a “duplex system.” Duplications of the collecting system are the most common congenital Congenital Chorioretinitis anomaly of the urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy. In these cases, a kidney will have 2 separate pelvicaliceal systems and 2 ureters Ureters One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the urinary bladder. Urinary Tract: Anatomy. Ureteral insertion into the bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess from the duplicated system is often abnormal as well. Most individuals are asymptomatic, though recurrent urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease (UTIs) or obstruction may occur.
  • Renal agenesis Agenesis Teratogenic Birth Defects: congenital Congenital Chorioretinitis absence of a kidney, specifically, renal parenchymal tissue. This absence results from disruption of metanephric development. Most individuals are asymptomatic (because they have another normally functioning kidney) and are diagnosed incidentally on imaging. Renal agenesis Agenesis Teratogenic Birth Defects is often associated with additional congenital Congenital Chorioretinitis anomalies.
  • Posterior urethral valves: persistence of the urogenital membrane, resulting in urethral obstruction in males. Affected infants often present in utero with severe bilateral hydronephrosis Hydronephrosis Hydronephrosis is dilation of the renal collecting system as a result of the obstruction of urine outflow. Hydronephrosis can be unilateral or bilateral. Nephrolithiasis is the most common cause of hydronephrosis in young adults, while prostatic hyperplasia and neoplasm are seen in older patients. Hydronephrosis seen on ultrasonography that causes pressure necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage of renal tissue and CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease in these children. There is a high likelihood that renal transplantation will be necessary.
  • Urachal fistula Fistula Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. Anal Fistula: persistence of the urachus Urachus An embryonic structure originating from the allantois. It is a canal connecting the fetal urinary bladder and the umbilicus. It is normally converted into a fibrous cord postnatally. When the canal fails to be filled and remains open (patent urachus), urine leaks through the umbilicus. Development of the Abdominal Organs. The urachus Urachus An embryonic structure originating from the allantois. It is a canal connecting the fetal urinary bladder and the umbilicus. It is normally converted into a fibrous cord postnatally. When the canal fails to be filled and remains open (patent urachus), urine leaks through the umbilicus. Development of the Abdominal Organs is known as the allantois Allantois An extra-embryonic membranous sac derived from the yolk sac of reptiles; birds; and mammals. It lies between two other extra-embryonic membranes, the amnion and the chorion. The allantois serves to store urinary wastes and mediate exchange of gas and nutrients for the developing embryo. Development of the Abdominal Organs earlier in development, and it connects to the bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess. Babies with a urachal fistula Fistula Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. Anal Fistula may leak urine from their umbilicus at birth.

Congenital Congenital Chorioretinitis anomalies of the reproductive system

  • Gartner duct cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change: benign Benign Fibroadenoma cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change that can be seen on either side of female reproductive organs (typically the upper vagina Vagina The vagina is the female genital canal, extending from the vulva externally to the cervix uteri internally. The structures have sexual, reproductive, and urinary functions and a rich blood supply, mainly arising from the internal iliac artery. Vagina, Vulva, and Pelvic Floor: Anatomy). These cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change represent remnants of the mesonephric ducts and are usually asymptomatic.
  • Müllerian anomalies: abnormal fusion of the müllerian/paramesonephric ducts can result in a variety of uterine, cervical, and vaginal anomalies. Individuals are often asymptomatic, though they may present with infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility or issues related to menstruation Menstruation The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle.
Malformations of the uterus

Illustration showing types of congenital malformations Congenital malformations Congenital malformations or teratogenic birth defects are developmental disorders that arise before birth during the embryonic or fetal period. The rate of incidence for children born alive is approximately 3%. Teratogenic Birth Defects of the uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy

Image by Lecturio. License: CC BY-NC-SA 4.0
Malformations of hymen

Normal parous hymen Hymen A thin fold of mucous membrane situated at the orifice of the vagina. Vagina, Vulva, and Pelvic Floor: Anatomy compared to common hymen Hymen A thin fold of mucous membrane situated at the orifice of the vagina. Vagina, Vulva, and Pelvic Floor: Anatomy malformations, including microperforate, septate, cribriform, and imperforate hymens

Image by Lecturio. License: CC BY-NC-SA 4.0
  • Hypospadias Hypospadias A birth defect due to malformation of the urethra in which the urethral opening is below its normal location. In the male, the malformed urethra generally opens on the ventral surface of the penis or on the perineum. In the female, the malformed urethral opening is in the vagina. Penile Anomalies and Conditions: congenital Congenital Chorioretinitis anomaly of the male urethra Male Urethra A tube that transports urine from the urinary bladder to the outside of the body in both the sexes. It also has a reproductive function in the male by providing a passage for sperm. Urinary Tract: Anatomy that is characterized by an abnormal location of the urethral meatus on the ventral surface of the penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis: Anatomy. The meatus may be located anywhere on the glans, penile shaft Penile Shaft Bowen Disease and Erythroplasia of Queyrat, scrotum Scrotum A cutaneous pouch of skin containing the testicles and spermatic cords. Testicles: Anatomy, or perineum Perineum The body region lying between the genital area and the anus on the surface of the trunk, and to the shallow compartment lying deep to this area that is inferior to the pelvic diaphragm. The surface area is between the vulva and the anus in the female, and between the scrotum and the anus in the male. Vagina, Vulva, and Pelvic Floor: Anatomy.

Disorders of sexual development

Disorders of sexual development (DSDs) are a group of conditions characterized by atypical sexual development in an individual, which may involve abnormalities in the structure and/or function of the internal reproductive organs and/or external genitalia. 

  • Congenital Congenital Chorioretinitis adrenal hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation: Increased formation of male sexual hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types ( androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens) with virilization of the external female genitals. Characterized by low levels of cortisol Cortisol Glucocorticoids, high levels of ACTH, and adrenal hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation.
  • Androgen insensitivity syndrome Androgen insensitivity syndrome Androgen insensitivity syndrome (AIS) is an X-linked recessive condition in which a genetic mutation affects the function of androgen receptors, resulting in complete (CAIS), partial (PAIS), or mild (MAIS) resistance to testosterone. All individuals with AIS have a 46,XY karyotype; however, phenotypes vary and include phenotypic female, virilized female, undervirilized male, and phenotypic male individuals. Androgen Insensitivity Syndrome ( AIS AIS Scoliosis): Mutations in the androgen receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors cause partial or complete resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing to testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens. Genotypically, affected individuals have a 46,XY karyotype Karyotype The full set of chromosomes presented as a systematized array of metaphase chromosomes from a photomicrograph of a single cell nucleus arranged in pairs in descending order of size and according to the position of the centromere. Congenital Malformations of the Female Reproductive System and testes Testes Gonadal Hormones present internally. Testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens levels are elevated, and some of this testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens is converted to estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy peripherally. Clinically, individuals with complete AIS Complete AIS Androgen Insensitivity Syndrome will present with no sexual hair and have normal-appearing external female genitalia. Individuals are usually assigned female gender Gender Gender Dysphoria at birth and will present at puberty Puberty Puberty is a complex series of physical, psychosocial, and cognitive transitions usually experienced by adolescents (11-19 years of age). Puberty is marked by a growth in stature and the development of secondary sexual characteristics, achievement of fertility, and changes in most body systems. Puberty with amenorrhea Amenorrhea Absence of menstruation. Congenital Malformations of the Female Reproductive System.
  • Aromatase Aromatase An enzyme that catalyzes the desaturation (aromatization) of the ring a of C19 androgens and converts them to C18 estrogens. In this process, the 19-methyl is removed. This enzyme is membrane-bound, located in the endoplasmic reticulum of estrogen-producing cells of ovaries, placenta, testes, adipose, and brain tissues. Aromatase is encoded by the cyp19 gene, and functions in complex with NADPH-ferrihemoprotein reductase in the cytochrome p450 system. Adipose Tissue: Histology deficiency: results in an inability to convert testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens to estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy, primarily causing virilization of the external genitalia in females.
  • 5α-reductase deficiency:  autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance disorder that impairs conversion of testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens to DHT DHT A potent androgenic metabolite of testosterone. It is produced by the action of the enzyme 3-oxo-5-alpha-steroid 4-dehydrogenase. Gonadal Hormones, preventing full development of the external genitalia in males. This disorder results in ambiguous genitalia Ambiguous Genitalia Primary Amenorrhea in 46,XY individuals at birth. 
  • Pure gonadal dysgenesis Gonadal dysgenesis A number of syndromes with defective gonadal developments such as streak gonads and dysgenetic testes or ovaries. The spectrum of gonadal and sexual abnormalities is reflected in their varied sex chromosome (sex chromosomes) constitution as shown by the karyotypes of 45, X monosomy (Turner syndrome); 46, XX (gonadal dysgenesis, 46xx); 46, XY (gonadal dysgenesis, 46, xy); and sex chromosome mosaicism. Their phenotypes range from female, through ambiguous, to male. This concept includes gonadal agenesis. Wilms Tumor: results in nonfunctional gonads Gonads The gamete-producing glands, ovary or testis. Hormones: Overview and Types. In 46,XX individuals, pure gonadal dysgenesis Gonadal dysgenesis A number of syndromes with defective gonadal developments such as streak gonads and dysgenetic testes or ovaries. The spectrum of gonadal and sexual abnormalities is reflected in their varied sex chromosome (sex chromosomes) constitution as shown by the karyotypes of 45, X monosomy (Turner syndrome); 46, XX (gonadal dysgenesis, 46xx); 46, XY (gonadal dysgenesis, 46, xy); and sex chromosome mosaicism. Their phenotypes range from female, through ambiguous, to male. This concept includes gonadal agenesis. Wilms Tumor presents with premature Premature Childbirth before 37 weeks of pregnancy (259 days from the first day of the mother’s last menstrual period, or 245 days after fertilization). Necrotizing Enterocolitis ovarian insufficiency (i.e., premature Premature Childbirth before 37 weeks of pregnancy (259 days from the first day of the mother’s last menstrual period, or 245 days after fertilization). Necrotizing Enterocolitis menopause Menopause Menopause is a physiologic process in women characterized by the permanent cessation of menstruation that occurs after the loss of ovarian activity. Menopause can only be diagnosed retrospectively, after 12 months without menstrual bleeding. Menopause) in otherwise normal-appearing females. In 46,XY individuals, the condition is known as Swyer syndrome Swyer syndrome Swyer syndrome is a disorder of sex development caused by a defect in the SRY gene on chromosome Y. The syndrome is characterized by complete testicular dysgenesis in an individual who has a 46,XY karyotype and is phenotypically female. Swyer Syndrome; without functional testes Testes Gonadal Hormones, testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens and MIF are not produced, so individuals have external female genitalia and normal müllerian structures Müllerian structures Congenital Disorders of Sexual Development. Affected individuals present in adolescence with primary amenorrhea Primary Amenorrhea Primary amenorrhea is defined as the absence of menstruation in a girl by age 13 years in the absence of secondary sex characteristics or by the age of 15 years with the presence of secondary sex characteristics. Etiologies can originate in the hypothalamic-pituitary-ovarian (HPO) axis or from anatomic abnormalities in the uterus or vagina. Primary Amenorrhea and lack of all secondary sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria characteristics.  
  • Klinefelter syndrome Klinefelter syndrome Klinefelter syndrome is a chromosomal aneuploidy characterized by the presence of 1 or more extra X chromosomes in a male karyotype, most commonly leading to karyotype 47,XXY. Klinefelter syndrome is associated with decreased levels of testosterone and is the most common cause of congenital hypogonadism. Klinefelter Syndrome: Chromosomal aneuploidy characterized by the existence of ≥ 1 extra X chromosomes Chromosomes In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. DNA Types and Structure in a male karyotype Karyotype The full set of chromosomes presented as a systematized array of metaphase chromosomes from a photomicrograph of a single cell nucleus arranged in pairs in descending order of size and according to the position of the centromere. Congenital Malformations of the Female Reproductive System (e.g., 47, XXY XXY Klinefelter syndrome is a chromosomal aneuploidy characterized by the presence of 1 or more extra X chromosomes in a male karyotype, most commonly leading to karyotype 47,XXY. Klinefelter syndrome is associated with decreased levels of testosterone and is the most common cause of congenital hypogonadism. Klinefelter Syndrome or 48,XXXY). Symptoms are not usually observed during childhood. During adulthood, individuals are typically tall males who present with gynecomastia Gynecomastia Gynecomastia is a benign proliferation of male breast glandular ductal tissue, usually bilateral, caused by increased estrogen activity, decreased testosterone activity, or medications. The condition is common and physiological in neonates, adolescent boys, and elderly men. Gynecomastia and infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility related to hypogonadism Hypogonadism Hypogonadism is a condition characterized by reduced or no sex hormone production by the testes or ovaries. Hypogonadism can result from primary (hypergonadotropic) or secondary (hypogonadotropic) failure. Symptoms include infertility, increased risk of osteoporosis, erectile dysfunction, decreased libido, and regression (or absence) of secondary sexual characteristics. Hypogonadism. Educational difficulties are also common.
  • Turner syndrome Turner syndrome Turner syndrome is a genetic condition affecting women, in which 1 X chromosome is partly or completely missing. The classic result is the karyotype 45,XO with a female phenotype. Turner syndrome is associated with decreased sex hormone levels and is the most common cause of primary amenorrhea. Turner Syndromechromosomal aneuploidy characterized by the absence of an X chromosome X chromosome The female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in human and other male-heterogametic species. Basic Terms of Genetics in a female karyotype Karyotype The full set of chromosomes presented as a systematized array of metaphase chromosomes from a photomicrograph of a single cell nucleus arranged in pairs in descending order of size and according to the position of the centromere. Congenital Malformations of the Female Reproductive System (e.g., 45,X0). Clinical manifestations include a characteristic phenotype Phenotype The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics (short stature, webbed neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, widely spaced nipples) and multiple anomalies usually involving the cardiac, renal, reproductive, skeletal, and lymphatic systems. Gonadal dysgenesis Gonadal dysgenesis A number of syndromes with defective gonadal developments such as streak gonads and dysgenetic testes or ovaries. The spectrum of gonadal and sexual abnormalities is reflected in their varied sex chromosome (sex chromosomes) constitution as shown by the karyotypes of 45, X monosomy (Turner syndrome); 46, XX (gonadal dysgenesis, 46xx); 46, XY (gonadal dysgenesis, 46, xy); and sex chromosome mosaicism. Their phenotypes range from female, through ambiguous, to male. This concept includes gonadal agenesis. Wilms Tumor and infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility are likely.
  • True hermaphroditism True hermaphroditism True hermaphroditism, or ovotesticular disorder of sexual development (ODSD), is characterized by the presence of an ovotesticular gonad that contains both ovarian and testicular elements. Individuals are usually born with ambiguous genitalia, but the diagnosis is rarely confirmed before puberty. The most common karyotype is 46,XX, and less often, 46,XY can be identified. True Hermaphroditism: presence of an ovotesticular gonad that contains both ovarian and testicular elements. Affected individuals are usually born with ambiguous genitalia Ambiguous Genitalia Primary Amenorrhea, and the internal structures depend on the adjacent gonadal tissue. The most common karyotype Karyotype The full set of chromosomes presented as a systematized array of metaphase chromosomes from a photomicrograph of a single cell nucleus arranged in pairs in descending order of size and according to the position of the centromere. Congenital Malformations of the Female Reproductive System is 46,XX.

References

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