June 18, 2010

Three Phase Ovulation

Prerequisite events
Through a process that takes approximately 375 days, or thirteen menstrual cycles, a large group of undeveloped primordial follicles dormant in the ovary is grown and progressively weaned into one preovulatory follicle. Histologically, the preovulatory follicle (also called a mature Graffian follicle or mature tertiary follicle) contains an oocyte arrested in prophase of meiosis I surrounded by a layer corona radiata granulosa cells, a layer of mural granulosa cells, a protective basal lamina, and a network of blood-carrying capillary vessels sandwiched between a layer of theca interna and theca externa cells. A large sac of fluid called the antrum predominates in the follicle. A "bridge" of cumulus oophorous granulosa cells (or simply cumulus cells) connects the corona-ovum complex to the mural granulosa cells.

Simply stated, the granulosa cells engage in bidirectional messenging with the theca cells and the oocyte to facilitate follicular function. Research is elucidating the specific factors used in follicular messenging at a rapid pace, but such discussion is beyond the scope of this article.

By the action of luteinizing hormone (LH), the preovulatory follicle's theca cells secrete androstenedione that is aromatized by mural granulosa cells into estradiol, a type of estrogen. High levels of estrogen have a stimulatory effect on hypothalamus gonadotropin-releasing hormone (GnRH) that in turn stimulates the expression of pituitary LH and follicle stimulating hormone (FSH).

The building concentrations of LH and FSH marks the beginning of the periovulatory phase.

Periovulatory phase
For ovulation to be successful, the ovum must be supported by both the corona radiata and cumulus oophorous granulosa cells. The latter undergo a period of proliferation and mucification known as cumulus expansion. Mucification refers to the secretion of a hyaluronic acid-rich cocktail that disperses and suspends the cumulus cell network in a sticky matrix around the ovum. This network stays with the ovum after ovulation and have been shown to be necessary for fertilization.

An increase in cumulus cell number causes a concomitant increase in antrum fluid volume that can swell the follicle to over 20mm in diameter. It forms a pronounced bulge at the surface of the ovary called the blister.

Ovulatory phase
Through a signal transduction cascade kicked off by LH, proteolytic enzymes are secreted by the follicle that degrade the follicular tissue at the site of the blister, forming a hole called the stigma. The ovum-cumulus complex leaves the ruptured follicle and out into the peritoneal cavity through the stigma, where it is caught by the fimbriae at the end of the fallopian tube (also called the oviduct). After entering the oviduct, the ovum-cumulus complex is pushed along by cilia, beginning its journey toward the uterus.

By this time, the oocyte has completed meiosis I, yielding two cells: the larger secondary oocyte that contains all of the cytoplasmic material and a smaller, inactive first polar body. Meiosis II follows at once but will be arrested in the metaphase and will so remain until fertilization. The spindle apparatus of the second meiotic division appears at the time of ovulation If no fertilization occurs, the oocyte will degenerate approximately twenty-four hours after ovulation

The mucous membrane of the uterus, termed the functionalis, has reached its maximum size, and so have the endometrial glands, although they are still non-secretory.

Postovulatory phase
The follicle proper has met the end of its lifespan. Without the ovum, the follicle folds inward on itself, transforming into the corpus luteum (pl. corpus lutea), a steriodogenic cluster of cells that produces estrogen and progesterone. These hormones induce the endometrial glands to begin production of the proliferative endometrium, the site of embryonic growth if fertilization occurs. The corpus luteum continues this paracrine action for the remainder of the menstrual cycle, maintaining the endometrium, before disintegrating into scar tissue during menses.