Part of the TeachMe Series

Gametogenesis

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Original Author(s): Reshma Joseph
Last updated: 12th February 2024
Revisions: 16

Original Author(s): Reshma Joseph
Last updated: 12th February 2024
Revisions: 16

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Gametogenesis occurs when a haploid cell (n) is formed from a diploid cell (2n) through meiosis. We call gametogenesis in the male spermatogenesis and it produces spermatozoa. In the female, we call it oogenesis.  It results in the formation of ova.

This article covers both oogenesis and spermatogenesis.

Spermatogenesis

In the Beginning

Males start producing sperm when they reach puberty, which is usually from 10-16 years old. Biological males continually produce sperm in large quantities (~200 million a day). This maximises the likelihood of sperm reaching the egg following ejaculation.

Sperm production occurs in the testes of the male, specifically in the seminiferous tubules. In the testicles, a blood testis barrier forms to keep the tubules separate from the systemic circulation.

Protecting the Sperm

Sertoli cells form the blood testis barrier. This is important in preventing substances found in blood from affecting the developing sperm. These products might include hormones or waste products.

It is also important as it prevents the immune system of the male from recognising the sperm as foreign – the sperm are genetically different from the male and will express different surface antigens.

Forming Functional Sperm

Spermatogonia are the initial pool of diploid cells that divide by mitosis to give two identical cells. One of these cells will be used to replenish the pool of spermatogonia – these cells are A1 spermatogonia. This replenishment of spermatogonia means that males are fertile throughout their adult life.

The other cell – type B spermatogonium – will eventually form mature sperm. Type B spermatogonia replicate by mitosis several times to form identical diploid cells linked by cytoplasm bridges, these cells are now known as primary spermatocytes.

Primary spermatocytes then undergo meiosis:

  • Meiosis I produces two haploid cells, known as secondary spermatocytes.
  • Meiosis II produces four haploid cells, known as spermatids.

Maturation

The cytoplasmic bridges break down and the spermatids are released into the lumen of the seminiferous tubule – a process called spermiation. The spermatids undergo spermiogenesis (remodelling and differentiation into mature spermatozoa) as they travel along the seminiferous tubules until they reach the epididymis.

From the seminiferous tubule, cells will travel to the rete testis. This acts to “concentrate” the sperm by removing excess fluid. Then, cells move to the epididymis where the sperm is stored and undergoes the final stages of maturation.

Spermatogenesis takes approximately 70 days, therefore for sperm production to be continuous and not intermittent, multiple spermatogenic processes are occurring simultaneously within the same seminiferous tubule, with new groups of spermatogonia arising every 16 days (spermatogenic cycle). Each of these populations of spermatogenic cells will be at different stages of spermatogenesis.

Following Ejaculation

Note that once sperm leave the male body and enter the female reproductive tract, the conditions cause the sperm to undergo capacitation.  This is the removal of cholesterol and glycoproteins from the head of the sperm cell to allow it to bind to the zona pellucida of the egg cell.

Fig 1 – Diagram showing the overall process of spermatogenesis

Oogenesis

Oogenesis differs from spermatogenesis in that it begins in the foetus before birth. Primordial germ cells (which originate in the yolk sac of the embryo) move to colonise the cortex of the primordial gonad. Replication by mitosis peaks at approximately 7 million by mid-gestation (~20 weeks).

Cell death occurs after this peak leaving roughly 2 million cells. Meiosis I begins before birth and forms primary oocytes. There is therefore a finite supply of ova.

Primary oocytes are arranged in the gonads as clusters. They have flattened epithelial cells surrounding them, and this is called the primary follicle.

During childhood, further atresia (cell death) occurs, leaving ~40,000 eggs at puberty.

Once puberty begins, several primary oocytes (15-20) begin to mature each month, although only one of these reaches full maturation to become an oocyte.

The primary oocytes undergo 3 stages:

  • Pre-antral
  • Antral
  • Preovulatory

Pre-Antral Stage

The primary oocyte is still in meiosis I but will grow dramatically in this stage. The follicular cells grow and proliferate to form a stratified cuboidal epithelium.

Now, we call these granulosa cells and they secrete glycoproteins. These chemicals form the zona pellucida around the primary oocyte.

Surrounding connective tissue cells also differentiate to become the theca folliculi, a specialised layer of surrounding cells that is responsive to LH and can secrete androgens under its influence.

Antral Stage

Fluid-filled spaces form between granulosa cells, these eventually combine to form a central fluid-filled space called the antrum.

We now call the follicles secondary follicles. In each monthly cycle, one of these secondary follicles becomes dominant and develops further under the influence of FSH, LH, and oestrogen. See our article on the menstrual cycle for more details.

Pre-Ovulatory Stage

The LH surge induces this stage and meiosis I is now complete. Inside the follicle, 2 unequally sized haploid cells form. One of the daughter cells receives far less cytoplasm than the other and forms the first polar body, which will not go on to form an ovum.

Another haploid cell is also formed, known as the secondary oocyte. Both daughter cells then undergo meiosis II.

An initial polar body will replicate to give two polar bodies but the secondary oocyte arrests in metaphase of meiosis II. This happens 3 hours prior to ovulation.

Ovulation

Now, the follicle has grown in size and is mature – it is called a Graafian follicle.

An LH surge occurs and increases collagenase activity. This is an enzyme that disrupts collagen. Therefore, there is a weakening of the follicular wall.

This, combined with muscular contractions of the ovarian wall, results in the ovum being released from the ovary. The ovum is then taken up into the fallopian tube via the fimbriae (finger-like projections of the fallopian tube).

Fertilisation – the Final Stage of Female Gametogenesis

The secondary oocyte will only complete meiosis II following fertilisation. Here, it gives off a third polar body. Following meiosis II, a fertilised egg results. If fertilisation doesn’t occur, the oocyte degenerates 24 hours after ovulation, remaining arrested in meiosis II.

If fertilisation does occur, peristaltic movements of the fallopian tube move the egg to the uterus where it can implant into the posterior uterine wall.

Fig 2 – Diagram demonstrating the overall process of oogenesis

Clinical Relevance – Polycystic Ovary Syndrome (PCOS)

PCOS is a common endocrine disorder that affects around 5-10% of premenopausal women. Excess androgen production and the presence of multiple immature follicles within a woman’s ovaries characterise this condition.

This condition has a poorly understood aetiology and patients can present with a wide variety of signs and symptoms, including:

  • Oligomenorrhoea/amenorrhoea
  • Infertility
  • Hirsutism
  • Obesity
  • Chronic pelvic pain
  • Depression

For a diagnosis, 2 criteria below must be met:

  1. Oligomenorrhoea and/or anovulation.
  2. Clinical/biochemical signs of hyperandrogenism.
  3. Polycystic ovaries on imaging.

To manage this, doctors need a patient-centred approach. This can include managing weight, reducing hyperandrogenism, and using medications. Medications prescribed could be the combined oral contraceptive pill (to manage oligo-/amenorrhoea) and metformin (to manage infertility).

Clinical Relevance – Errors in Meiosis

Errors in gametogenesis can lead to several chromosomal abnormalities including non-disjunction or polyploidies. Non-disjunction occurs when chromosomes fail to separate appropriately. Polyploidy occurs when there are more than 2 copies of a homologous chromosome in a cell.

Errors in gametogenesis can lead to:

  • Trisomies
    • Down’s Syndrome – trisomy 21
    • Edward’s Syndrome – trisomy 18
    • Patau’s Syndrome – trisomy 13

Obstetricians can aid parents in screening for chromosomal abnormalities antenatally.