Time period: week 12 to menopause
Female germ cells proliferate by mitosis in the ovaries to form a large number of oogonia. These cells are diploid, contain two X sex chromosomes, and will become haploid mature oocytes via the process of oogenesis. This process is similar to spermatogene- sis but has some significant differences.
The germ cells that will form the female gametes (oocytes) are derived from germ cells that migrate from the yolk sac into the site of early gonad formation (see Chapter 38).
The ovaries are a pair of organs that produce oocytes and reproduc- tive hormones. They lie near the openings of the uterine tubes (also known as the Fallopian tubes or oviducts) that extend from the uterus. Finger‐like projections from the uterine tubes called fimbriae collect oocytes when they are expelled from the ovaries. The oocyte is carried into and along the uterine tube for fertilisation and subse- quent implantation into the wall of the uterus.
The adult ovary is predominantly made up of connective tissue that supports a large number of follicles. Blood vessels and nerves are concentrated within the central medulla whereas follicles are found in the outer cortex, in varying stages of development.
Oogonia begin oogenesis by entering meiosis I in week 12 of embryonic development (Figure 9.1). During meiosis I the cell is known as the primary oocyte, and is surrounded by a thin layer of squamous epithelial cells. This structure is a follicle, and in its very early stage is called a primordial follicle. The primary oocyte at this stage is developmentally arrested in prophase of meiosis I. This pause in development may continue for 45 years or more.
The number of primordial follicles vastly increases during the foetal period but many degenerate, leaving around 400,000 follicles available at puberty. After birth no new oocytes form.
With the onset of puberty some of the stalled primary oocytes continue oogenesis each month (Figure 9.1).
The primary oocyte becomes larger and the follicular cells around it become cuboidal and the layer thickens. The follicle is now a primary follicle (Figure 9.2).
The oocyte and the granulosa (follicle) cells produce a layer of glycoproteins on the surface of the oocyte called the zona pellucida.
When the follicle forms more than one layer of granulosa cells it is called a secondary follicle.
One follicle continues to develop and grow, and the others degen- erate. It is not clear how one follicle is chosen over the others.
A cavity called the antrum forms between the layers of granu- losa cells, and the mass of follicular cells is now termed the cumulus oophorus.
The connective tissue cells of the ovary around the follicle respond by differentiating and forming two new layers: the theca interna and the theca externa. The theca interna has a hormonal role, and the theca externa a supportive role. This follicle is now a mature vesicular follicle or Graafian follicle.
The thecal and granulosa cells of the developing follicles pro- duce oestrogens that cause the thickening of the endometrial lin- ing of the uterus and other preparations for receiving a fertilised oocyte. This occurs from days 5 to 14 of the menstrual cycle (see Figure 5.1 and Chapter 12).
The primary oocyte of the Graafian follicle responds to surges in follicle stimulating hormone (FSH) and luteinising hormone (LH) produced by the pituitary gland on days 13–14 of the menstrual cycle by resuming meiosis I and continuing its stalled cell division (Figure 9.1).
When the oocyte divides it forms one large cell and one smaller remnant of the division known as a polar body. At the end of meiosis I the oocyte has become a secondary oocyte.
Polar bodies are small, non‐functional cells. They receive very little of the available cytoplasm and degenerate soon after division. In this way the oocyte is able to retain its size but discard chromo- somal material to become a haploid cell ready for fertilisation.
One polar body is formed with meiosis I and two polar bodies are formed with meiosis II.
The secondary oocyte begins meiosis II but this division is again halted, this time during metaphase II. Meiosis II will only continue if the oocyte is fertilised.
With ovulation the secondary oocyte is passed into the uterine tube, but the follicle remains within the ovary (Figure 9.2). At this stage the follicle is very large and makes up a significant portion of the ovary. This follicle becomes the corpus luteum.
In response to LH the corpus luteum produces progesterone, oestrogens and other hormones causing the endometrium of the uterus to thicken further, develop its vasculature, form glands and prepare for implantation.
If fertilisation does not occur the corpus luteum degenerates about 14 days later and becomes a scar tissue remnant of itself called the corpus albicans. Hormone production ceases and menstrua- tion begins as the thickened endometrium is shed.
The primary oocyte may be arrested in meiosis I throughout life for 40–50 years if it is not triggered to continue development until a menstrual cycle late in reproductive life. DNA fragmentation within those stored oocytes is more common in older women as DNA damage increases with time. This may be the reason for reduced fertility with increasing age.
Knowledge of the sex hormones’ effects on follicle development have allowed the invention of the oral contraceptive pill. High levels of oestrogens and progesterone inhibit gonadotrophin releasing hormone (GnRH) and subsequently LH and FSH release. Decreased levels of FSH mean that the follicle is not stimulated to develop, and the absence of an LH surge prevents ovulation occurring.
Chemotherapy and radiotherapy can destroy primordial ovarian follicles. As there is a finite reserve of oocytes formed prenatally, which cannot be replenished after treatment, the cryopreservation of oocytes before treatment begins should be considered. Frozen ay be used for in vitro fertilisation at a later date if the patient becomes infertile.