Ovulation and Completion of Meiosis

Ovulation is the release of a secondary oocyte from the mature ovarian follicle. It is directly, causally linked to resumption of meiosis from the first, prolonged arrest point. Hormonal triggering of ovulation and resumption of the oocyte's own meiotic division are tightly coupled, occurring in the same narrow window of time. They are not independent processes that merely coincide.

Ovulation is triggered by a sharp, sustained surge in luteinising hormone, LH, released from the anterior pituitary gland. The surge occurs in response to rising oestrogen levels produced by the maturing dominant follicle over the preceding days of the follicular phase of the menstrual cycle.

The LH surge acts directly on the dominant follicle, specifically on the oocyte-cumulus complex within it. It is the immediate trigger for two closely linked events:

• Resumption of meiosis within the primary oocyte, which had remained arrested at diplotene of prophase I since fetal life.
• The follicular structural and enzymatic changes required for physical rupture of the follicle wall and release of the oocyte-cumulus complex from the ovary.

In response to the LH surge, the primary oocyte within the dominant follicle resumes meiosis. It proceeds rapidly through the remainder of prophase I, diakinesis, and through metaphase I and anaphase I of meiosis I.

Completion of meiosis I produces a markedly unequal division, as in the oogenesis sequence. The secondary oocyte retains almost the entire original cytoplasmic volume. The first polar body receives an equal haploid chromosome complement but only a negligible amount of cytoplasm. This occurs in the immediate period preceding ovulation, timed to be essentially complete by the point of follicular rupture.

At ovulation, the follicle wall ruptures. The oocyte-cumulus complex (the secondary oocyte with its immediately surrounding corona radiata cells) is released from the ovarian surface into the peritoneal cavity.

It is normally captured by the fimbriae of the adjacent uterine tube and swept into the tube's ampulla, the usual site of fertilisation.

Critically, the secondary oocyte released at ovulation has completed meiosis I but not meiosis II. Immediately after entering meiosis II, it arrests again, this time at metaphase II. The oocyte is ovulated and available for fertilisation in this partially completed meiotic state, not as a fully mature, meiotically complete haploid cell.

A specific cytoplasmic regulatory mechanism within the oocyte maintains this second arrest. It stabilises the metaphase II spindle and prevents further cell cycle progression. The arrest persists for as long as fertilisation does not occur. An unfertilised secondary oocyte stays arrested at metaphase II for a limited period after ovulation, then degenerates and is lost, without ever completing meiosis.

Meiosis II is completed only if, and only at the moment, a spermatozoon successfully penetrates the secondary oocyte at fertilisation. Sperm penetration activates the oocyte, releasing it from metaphase II arrest. The remainder of meiosis II, anaphase II and telophase II, then completes rapidly. This produces a mature ovum and a second polar body. The final surplus haploid chromosome set is discarded, while essentially all the cytoplasm is retained for the zygote.

Female meiosis therefore remains incomplete unless and until fertilisation occurs. Male gametogenesis has no equivalent. All four meiotic products of a single primary spermatocyte independently complete both meiotic divisions as a routine part of spermatogenesis, irrespective of whether fertilisation ever follows.

A practical consequence follows. Strictly speaking, an oocyte is never fully, definitively haploid with the entire meiotic sequence completed before fertilisation takes place. Between ovulation and sperm entry it exists as a secondary oocyte, arrested partway through its second meiotic division.