Gametogenesis

Gametogenesis is the development of gametes from primordial germ cells. This process differs between the sexes. In males, spermatogenesis produces spermatozoa. In females, oogenesis results in an ovum. The process starts with the migration of primordial germ cells from the yolk sac to the gonadal ridge. Oogenesis starts during the embryonic and fetal periods, whereas spermatogenesis starts at puberty. However, the phases of gametogenesis are similar, with germ cells progressing through mitosis, meiosis I, meiosis II, and maturation. This process results in gametes that are haploid, with 23 chromosomes.

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Overview

Emigration of germ cells

  • Primordial germ cells (PGCs) originate from the endoderm of the yolk sac.
  • Journey along the hindgut → reach gonadal ridge → cells now called gametogonia 
  • Take up association with primordial sex cords

Gametogenesis

  • Gametogonia and gametogenesis differ between sexes:
    • Females: oogonium → oogenesis
    • Males: spermatogonium → spermatogenesis
  • Cells generally follow the same phases:
    • Mitosis
    • Meiosis I
    • Meiosis II
    • Maturation/differentiation
  • These phases lead cells through the following development:
    • Gametogonium (diploid, 46 chromosomes)
    • Primary gametocyte (diploid, 46 chromosomes)
    • Secondary gametocyte (haploid, 23 chromosomes)
    • Gametid (haploid, 23 chromosomes)
    • Gamete (haploid, 23 chromosomes)
Gametogenesis in males and females

Gametogenesis in males and females:
Diploid gametogonia undergo mitosis. Some daughter cells will remain as gametogonia, while others differentiate into primary gametocytes. From there, meiosis I occurs, resulting in secondary gametocytes that are haploid. Meiosis II leads to gametids, with 1 representative strand of DNA from each chromosome. Gametids undergo a separate process for differentiation/maturation to produce mature gametes.

Image by Lecturio.

Oogenesis

Oogenesis is the process of ovum production from PGCs. 

Formation of ovum

  • Phases of oogenesis:
    • Mitosis: 
      • Oogonium → primary oocyte
      • Ploidy: diploid
      • 46 chromosomes
    • Meiosis I: 
      • Primary oocyte → secondary oocyte and 1st polar body
      • Ploidy: diploid → haploid
      • 46 → 23 chromosomes
    • Meiosis II: 
      • Secondary oocyte → ootid and 2nd polar body
      • Ploidy: haploid
      • 23 chromosomes
    • Maturation: ootid → ovum
  • Note: Unlike in spermatogenesis, cell division is uneven in oogenesis, resulting in a single ovum and polar bodies.
  • Time line:
    • Initiated in the embryonic and fetal periods.
    • Halts in prophase of meiosis I
    • Resumes during puberty
    • A 2nd arrest occurs in the metaphase of meiosis II.
    • Resumes again after fertilization
    • Process continues monthly until menopause.

Follicle development

Folliculogenesis is a complex process in which an ovarian follicle, containing an oocyte, matures through several stages.

  • Primordial follicle:
    • Develops in ovaries during the fetal period
    • Oogonia become surrounded by somatic epithelial cells from the genital ridge.
  • Primary follicle:
    • Contains a primary oocyte
    • A glycoprotein layer is created (zona pellucida).
    • Follicular cells proliferate to become the granulosa cell layer.
  • Secondary follicle: 
    • This stage is responsive to gonadotropins.
    • Granulosa cell layer grows.
    • Recruitment of thecal cells → surround basement membrane
  • Tertiary follicle:
    • Granulosa cells produce:
      • Secretions → create an antrum
      • Estrogen
    • Granulosa cells around the oocyte become the cumulus oophorus.
    • Thecal cells differentiate into:
      • Theca interna: contains small vessels and glandular cells; produce testosterone → converted to estrogen by granulosa cells
      • Theca externa: stabilizes follicles; derived from connective tissue
  • Mature (graafian) follicle:
    • Only 1 follicle will reach this stage each cycle.
    • Primary oocyte → secondary oocyte just before ovulation
    • Antrum enlarges (makes up most of the follicle)
    • Innermost layer of the cumulus oophorus → corona radiata
  • Corpus luteum:
    • Formed after oocyte release
    • Center contains a blood clot formed after ovulation.
    • Granulosa and theca cells produce progesterone.
    • Atrophies if pregnancy does not occur.
The stages of folliculogenesis

The stages of folliculogenesis:
Note the progression of follicular cell proliferation, thecal cell differentiation, and antrum enlargement.

Image by Lecturio.

Ovulation

  • Occurs when luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels peak
  • Cumulus oophorus cells loosen → allows oocyte and corona radiata to detach from the follicle
  • Proteolytic enzymes weaken the follicle wall.
  • Rupture of the follicular wall → release of the oocyte

Related videos

Spermatogenesis

Spermatogenesis is the process of sperm production from PGCs.

Location

Overview:

  • Spermatogenesis takes place in the seminiferous tubules in the testes. 
  • Prepuberty, seminiferous tubules consist of:
    • Sertoli cells
    • PGCs (spermatogonia)

Sertoli cells:

  • Control the environment within the seminiferous tubules
  • Help regulate spermatogenesis
  • Contain FSH and androgen receptors → necessary for stimulating spermatogenesis
  • Secrete:
    • Antimüllerian hormone (AMH) → regression of müllerian ducts during embryonic development
    • Inhibin B → inhibits FSH secretion → helps with regulating hormone levels
  • Form the blood–testis barrier → protects sperm development from:
    • Immune system
    • Other substances in the blood (e.g., toxins, hormones)

Formation of spermatozoa

  • Onset: puberty
  • Induced by FSH and testosterone (produced by Leydig cells in response to LH)
  • Occurs in phases:
    • Mitosis: 
      • Spermatogonia → primary spermatocyte
      • Ploidy: diploid
      • 46 chromosomes
    • Meiosis I: 
      • Primary spermatocyte → secondary spermatocyte
      • Ploidy: diploid → haploid
      • 46 → 23 chromosomes
    • Meiosis II: 
      • Secondary spermatocyte → spermatid
      • Ploidy: haploid
      • 23 chromosomes
    • Spermiogenesis (maturation): spermatid → spermatozoa
  • Mature spermatozoa are released into the lumen of the seminiferous tubules → stored in the epididymis
  • Entire process takes approximately 2 months
The process of spermatogenesis

The process of spermatogenesis as the cells progress from primary spermatocytes to secondary spermatocytes to spermatids to sperm

Image: “Illustration from Anatomy & Physiology, Connexions” by OpenStax College. License: CC BY 4.0

Structure of spermatozoa

Spermiogenesis results in characteristic morphologic changes associated with spermatozoa.

  • Head:
    • Nucleus: 
      • Contains chromosomes
      • Condensed
    • Acrosome: 
      • Cap-like structure covering the anterior head region
      • Produced by transformation of the Golgi apparatus
      • Contains enzymes needed for fertilization
  • Body (mid-piece):
    • Contains mitochondria
    • Provides ATP for movement of the flagellum
  • Tail (flagellum): 
    • Provides motility
    • Consists of microtubules
Structure of sperm

Structure of sperm

Image: “Structure of Sperm: Sperm cells are divided into a head, containing DNA; a mid-piece, containing mitochondria; and a tail, providing motility. The acrosome is oval and somewhat flattened.” by OpenStax College. License: CC BY 4.0

Capacitation

  • Spermatozoa are functionally immature after spermiogenesis.
  • A final maturation process is required to: 
    • Become metabolically active
    • Fertilize an ovum
  • Process:
    • Begins in the epididymis
    • Ends in the female reproductive tract
  • Changes include:
    • Motility
    • Enzyme content of the acrosome
    • Cell surface proteins

Clinical Relevance

  • Trisomy 21 (Down syndrome): chromosomal disorder that can result from an error in meiosis during gametogenesis. Affected individuals have characteristic craniofacial and musculoskeletal features, as well as multiple medical anomalies involving the cardiac, GI, ocular, and auditory systems. Ultimately, karyotyping confirms the diagnosis in the prenatal or postnatal period. There is no cure for Down syndrome. Treatment is based on the clinical manifestations present. 
  • Trisomy 18 (Edwards syndrome): chromosomal disorder that can result from an error in meiosis during gametogenesis. Trisomy 18 is the 2nd most common trisomy, with a predominance in girls. Characteristic features include intrauterine growth restriction, cardiac defects, clenched fists with overlapping fingers, and rocker bottom feet. Diagnosis is made by karyotype analysis. No treatment is available, and most affected individuals do not survive beyond 1 year of life.
  • Trisomy 13 (Patau syndrome): chromosomal disorder that can result from an error in meiosis during gametogenesis. Trisomy 13 is the 3rd most common trisomy. Clinical features include brain and spinal cord malformations, cardiac defects, eye defects, cleft lip/palate, and hypotonia. Diagnosis is made by karyotype analysis. No treatment is available, and most affected individuals do not survive beyond 1 year of life.

References

  1. Gilbert, S.F. Spermatogenesis (2000). In Developmental Biology, 6th ed. Sunderland (MA): Sinauer Associates. https://www.ncbi.nlm.nih.gov/books/NBK10095/
  2. Matsumoto, A.M., Anawalt, B.D. (2020). Male reproductive physiology. UpToDate. Retrieved September 5, 2021, from https://www.uptodate.com/contents/male-reproductive-physiology
  3. Suede, S.H., Malik, A., Sapra, A. (2021). Histology, spermatogenesis. StatPearls. Retrieved September 5, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK553142/
  4. Waters, M., Tadi, P. (2020). Genetics, female gametogenesis. StatPearls. Retrieved September 9, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK555917/
  5. Holesh, J.E., Bass, A.N., Lord, M. (2021). Physiology, ovulation. StatPearls. Retrieved September 9, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK441996/
  6. Desai, N., Ludgin., et al. (2013). Female and male gametogenesis. Chapter 3 of Falcone, T., Hurd, W.W. (Eds.), Clinical Reproductive Medicine and Surgery. Springer Science+Business Media New York. https://www.clevelandclinic.org/ReproductiveResearchCenter/docs/publications/180_Female_and_male_gametogenesis.pdf
  7. Swerdloff, R.S., Wang, C. (2020). The testis and male hypogonadism, infertility, and sexual dysfunction. In: Goldman, L., Schafer, A. I. (Eds.), Goldman-Cecil Medicine, 26th ed., pp. 1537–1547. Elsevier.

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