Preparation For Pregnancy
Professor Alfred Cuschieri
Department of Anatomy, University of Malta
Objectives:
o Distinguish between FSH, LH and chorionic gonadotrophin, and where they are synthesised
o Distinguish between primordial, primary and secondary follicles
o Name the functions of the granulosa cells and the theca folliculi
o Describe the structure of the oocyte immediately after ovulation
o Name the functions of oestrogen and progesterone
o Correlate hormonal changes with the phases of the menstrual cycle
o State how the endometrium is affected by a pregnancy
o Outline the mechanisms of action of substances that inhibit and others that stimulate ovulation or spermatogenesis.
o Explain the hormonal changes in post-menopausal
Cyclic Changes In The Female Genital System
The female genital system undergoes a series of cyclic interdependent changes that bring about ovulation and prepare the genital tract for an eventual pregnancy. If pregnancy does not ensue a new cycle commences at approximately monthly intervals. These changes affect
1. The development of the oocyte and ovarian follicle, culminating in ovulation and the formation of a corpus luteum (The ovarian cycle)
2. The uterine endometrium culminating in menstruation if pregnancy does not ensue (The menstrual cycle)
3. A series of hormonal changes that control the cycle:
a. Gonadotrophin releasing hormone (GnRH), released by the hypothalamus and acting on the gonadotrophs of the anterior pituitary.
b. Follicle Stimulating Hormone (FSH), and Luteinising Hormone (LH) secreted by the gonadotrophs of the anterior pituitary. These hormones are called gonadtrophins because they act on the gonads and bring about the changes in the ovarian cycle
c. Oestrogen and progesterone, secreted by the ovarian follicular cells and corpus luteum respectively act on the endometrium stimulating the cyclical changes of the menstrual cycle.
All these cyclical changes are inter-related and inter-dependent. The cycle begins when all the hormones are at their lowest levels and the development of primary follicles while the endometrium commences menstruation. For practical purposes day 0 of the cycles corresponds to the first day of menstruation.
The cyclical changes are divided into 3 phases as follows:
1. The Oestrogen phase extends from day 0 to the time of ovulation, approximately on day 14. The oocyte and follicles undergo the following changes:
a. Primordial follicles (Days 0 to 3). These consist of a primary oocyte surrounded by a layer of flattened follicular cells. The oocyte is in the diplotene stage of meiosis I, and in meiotic arrest at this stage since foetal life. A rise in GnRH stimulates a gradual rise in the level of FSH. This in turn stimulates 5 to 20 primordial follicles to begin to develop.
b. Primary follicles (Days 3 to 8). These consist of a primary oocyte surrounded by a layer of cubical follicular cells. The oocyte is covered by a number of micovilli, and the follicular cells have processes that contact the oocyte plasma membrane and have gap junctions between them.
c. Secondary follicles (Days 8 to 10). The oocyte influences the granulosa cells to proliferate and organize the development of a secondary follicle
i. The follicular cells proliferate and become multilayered – they may also be called granulosa cells, which secrete oestrogens The granulosa cells are stimulated to proliferate by the action of activin, a signaling protein that is a member of the family of transforming growth factor-b (TGF-b), which is released by the oocyte. FSH also acts on the granulosa cells, and enhances the action of activin. The granulosa cells secrete Meiosis inhibiting factor (MIF).
ii. A follicular antrum forms by accumulation of fluid between the follicular cells
iii. A zona pellucida forms around the primary oocyte. This consists of glycoprotein and glycosaminoglycans. It is secreted jointly by the oocyte and the follicular cells. The processes between the follicular cells and the oocyte are maintained through the zona pellucida.
iv. The theca folliculi is derived from the ovarian stroma surrounding the follicle and consists of
- a theca interna, which is cellular and secretes androgens, which are then converted to oestrogen by the granulosa cells
- a theca externa, which is fibrous.
v. Although many follicles begin to develop, only one usually becomes dominant, while the rest degenerate
d. Graafian follicle (Days 11 to 14).
i. The antrum containing liquor folliculi enlarges until it is about 2 cm in diameter
ii. The cumulus oophorus is a mass of follicular cells that surround the oocyte and projects into the antrum
iii. The membrana granulosa is the layer of follicular cells that surrounds the antrum
iv. A surge of LH occurs at mid-cycle (day 14) stimulates:
- Production of maturation-promoting factor
- Release of the oocyte from meiotic arrest
- Withdrawal of processes and gap junctions of the follicular cells
- Withdrawal of the oocyte microvilli, forming a perivitelline space
- Completion of the first meiotic division to form a secondary oocyte
- Extrusion of the first polar body
- Secretion of progesterone by the granulosa and theca interna
- The Graafian follicle to point and bulge on the surface of the ovary
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2. Ovulation occurs when the Graafian follicle ruptures, releasing the oocyte. At the time of