Oogenesis

Oogenesis is the process by which oogonia, the female germ cell population, are transformed into mature oocytes capable of fertilisation. Its pattern differs fundamentally from spermatogenesis in timing, continuity and the number of functional gametes produced. Most distinctively, the female germ cell undergoes extraordinarily prolonged periods of meiotic arrest.

Oogonia are the diploid germ cell population within the developing ovary. They derive from the primordial germ cells that colonised the genital ridge during early embryonic development. They proliferate extensively by mitosis exclusively during fetal life.

This mitotic proliferation is entirely prenatal and time-limited. By around month 5 of fetal life, the total oogonial population reaches its maximum, estimated at several million cells. Essentially no further oogonial mitotic division occurs for the remainder of that individual's life.

This contrasts directly with spermatogonia, which continue dividing by mitosis throughout adult male life. The entire female gamete-producing cell population a woman will ever have is established before she is born.

Beginning around month 3 of fetal life and continuing through month 7, oogonia progressively enter meiosis I and become primary oocytes. Here the defining feature of oogenesis first appears.

Primary oocytes proceed through the early substages of prophase I, including synapsis and crossing over. They then arrest at the diplotene substage of prophase I.

They remain arrested at this exact point for a remarkably long period, in most cases for decades. Meiosis resumes only if and when that oocyte is later recruited for ovulation.

Continued oogonial mitotic proliferation occurs earlier in fetal life. Extensive subsequent attrition of primary oocytes then occurs through atresia, which is programmed degeneration. The total primary oocyte population declines substantially from its fetal peak. By birth only around 1 to 2 million primary oocytes remain, arrested in prophase I.

The number continues to decline progressively through childhood and reproductive life, through ongoing atresia. Only a few hundred to a few thousand remain by the time of menopause. The great majority will never be ovulated.

The prolonged first arrest, at diplotene of prophase I, is the most distinctive single feature of oogenesis. It lasts from before birth until the oocyte is recruited for ovulation, potentially several decades later.

This duration has direct and significant clinical consequences. The prolonged arrest is understood to be a major contributing factor to the increasing risk of meiotic error, particularly nondisjunction, with advancing maternal age.

Meiosis resumes from this first arrest point only in the ovarian follicle selected for ovulation in a given menstrual cycle. It resumes only shortly before that cycle's ovulation.

The great majority of primary oocytes present at any time in a woman's reproductive life therefore remain arrested at diplotene indefinitely. They are never called upon to resume meiosis at all.

A primary oocyte is recruited and completes meiosis I shortly before ovulation. The division is markedly unequal in cytoplasmic distribution, even though the chromosomal material is divided correctly according to standard meiotic principles.

One daughter cell, the secondary oocyte, retains almost all of the original cytoplasm and its associated nutrient and organelle content. The other daughter cell, the first polar body, receives an equal haploid chromosome complement but only a minimal, functionally negligible amount of cytoplasm.

The secondary oocyte proceeds immediately into meiosis II, but arrests again, this time at metaphase II. Ovulation occurs in this state, with a secondary oocyte arrested at metaphase II.

The oocyte released at ovulation has therefore completed only meiosis I. It is only partway through meiosis II when it leaves the ovary.

Polar bodies are the small, cytoplasm-poor byproducts of the two unequal meiotic divisions of oogenesis.

• The first polar body is produced at completion of meiosis I.
• A second polar body is produced if fertilisation occurs. It forms when the secondary oocyte completes meiosis II following sperm penetration.

Polar bodies contain a correct haploid chromosome complement but essentially no functional cytoplasm. They are not capable of further development or fertilisation.

Their sole biological role is to allow the primary oocyte to discard half of its chromosomal material, as meiosis requires. The oocyte keeps almost its entire cytoplasmic volume, nutrient stores and organelles for the single functional gamete, the mature oocyte, that oogenesis produces.

Oogenesis involves two sequential, very differently timed periods of meiotic arrest, unlike any stage of spermatogenesis.

• The first arrest, at diplotene of prophase I, begins during fetal life. It persists until that individual oocyte is recruited for ovulation, potentially decades later.
• The second arrest, at metaphase II, begins shortly before ovulation. It persists until fertilisation occurs.

If fertilisation does not occur, the secondary oocyte never completes meiosis II and instead degenerates.

Meiosis II is therefore only ever completed by a fertilised oocyte. Completion of female meiosis depends mechanistically on the arrival of a spermatozoon. The male gametogenic sequence has no equivalent dependency.