Physiology of the Reproductive Tract

Published on 10/03/2015 by admin

Filed under Obstetrics & Gynecology

Last modified 22/04/2025

Print this page

This article have been viewed 1524 times

Chapter 3 Physiology of the Reproductive Tract

Ovulation

Female reproductive physiology

During reproductive life, the cyclical development of ovarian follicles is the dominant process. The associated hormonal production has significant effects on the female genital tract, hypothalamus and pituitary.

In men, gamete production continues throughout life, whereas women develop their life supply of gametes during intrauterine life. See Chapter 1. The numbers decline even before birth, and there will be around 300,000 remaining at puberty.

The surface of the ovary is covered by a cuboidal ‘germinal’ epithelium. This layer is contiguous with the peritoneum. Underneath the epithelial layer is a thin layer of fibrous tissue, beneath which is the true cortex.

The cortex consists of a specialised stroma or parenchyma; the primordial follicles are embedded in this layer.

The primordial follicle consists of a primary oocyte surrounded by a single layer of flattened cells, the pre-granulosa, said to be derived from the cells of the sex cords.

The pre-granulosa cells become cuboidal and proliferate to form a shell several layers thick. At this stage, a hyaline membrane is formed immediately around the ovum – the zona pellucida.

The granulosa cells continue to proliferate until the follicle is approximately 200 μm in diameter. Fluid spaces now appear between the granulosa cells. They coalesce to form a cavity, the antrum, pushing the ovum to one side. The granulosa cells immediately surrounding the ovum are now known as the corona radiata, and the whole mass of cells in this situation is termed the cumulus oophorus.

At the same time, the surrounding parenchymal cells arrange themselves concentrically around the follicle. The cells opposite the ovum become smaller and more epithelial in appearance. As the follicle increases in size, this epithelial change spreads to the parenchymal cells around the circumference of the follicle. This band of cells constitutes the theca interna. The cells are surrounded by sinusoidal capillaries, thus forming an endocrine gland-like structure. External to this band, the parenchymal cells are also arranged concentrically but retain their fusiform shape.

The follicle, which is called the Graafian follicle, continues to grow to a size of more than 1.0 cm. Approximately four to five follicles may attain this size and project on the surface of one ovary. One of these follicles ruptures on the surface, releasing the ovum surrounded by some of the granulosa cells. Ovulation is initiated by the gonadotrophin surge occurring in response to the long loop oestradiol positive feedback. Vascular changes occur in the follicle within minutes of the luteinising hormone (LH) surge, possibly due to release of histamine or other kinins. Proteolytic enzymes are released and collagen disintegrates. It is likely that insulin-like growth factors (IGFs) such as IGF-1 regulate granulosa differentiation. It is not known whether ovarian adrenergic nerve fibres or smooth muscle cells are involved. Prostaglandins may play a role.

From fetal life to the menopause, follicular growth is continuous. Oestrogen initiates the process. Three phases can be distinguished:

Normally only one follicle ovulates. Cohorts of follicles enter the growth phase in succession, and follicles of various sizes are usually found. The follicle destined to ovulate is among a cohort stimulated to grow by follicle stimulating hormone (FSH) secreted by the pituitary during the last few days of the cycle. Only about 400 of the original 2 million follicles will reach the ovulatory stage and there is continuous wastage of follicles from fetal life onwards.

Ovulation is the final event in a step-wise stimulatory mechanism starting in the hypothalamus, which contains gonadotrophin releasing cells. These produce a gonadotrophin releasing hormone (GnRH).

Hypothalamus

Endometrial cycle

GnRH

This substance begins to be secreted just before puberty in pulses every hour and continues in this fashion for the rest of life. There is only a single releasing hormone responsible for the production of both FSH and LH. The type of gonadotrophin secreted by the pituitary appears to be determined by other factors related to the phase of the menstrual cycle.

FSH

FSH stimulates follicular development and production of oestrogen. A peak of FSH is reached by the 6th day of the menstrual cycle. At this point, the rising oestrogen has a negative feedback effect, and the FSH curve languishes for a day or two; then, it resumes its upward trend to achieve a second peak at the time of ovulation on day 12.

Inhibin is produced by the corpus luteum and inhibits the production of FSH while it is active. As a result, follicular growth ceases. After the 22nd day, when the corpus luteum becomes inactive, FSH secretion and growth of follicles are resumed.

LH

Very low levels of LH are recorded in the early part of the cycle, but a sudden surge, coinciding with the second peak of FSH, induces ovulation and formation of the corpus luteum. Shortly thereafter, the level of LH returns to pre-ovulatory values.

Ovulation

FSH production is usually inhibited by rising oestradiol levels; however, a change occurs as the dominant follicle develops. Changes occur in the receptors on the follicular cells as the cycle progresses. Although the blood FSH is temporarily reduced after the 6th day, the larger follicles have accumulated sufficient FSH to maintain growth and oestrogen production. As the blood concentration of oestrogen continues to increase, it appears to reach a critical level at the 12th day, and in place of its usual negative feedback effect on the pituitary, it suddenly exerts a positive feedback effect with a consequent rise in FSH (the second peak) and secretion of LH.

Gonadotrophin Secretion (International Units per Litre)

Cyclical ovarian hormonal changes

Oestrogens

The plasma values of the three main oestrogens, oestradiol, oestrone and oestriol, are almost parallel throughout the cycle. The levels are low during menstruation and very gradually increase. Significant changes are noted around the 7th–8th day of the cycle, the levels rising to a maximum around the 12th day – ovulation peak. A fall occurs 24 h later, followed by a further increase a week later – the maximum phase of corpus luteum activity.

Progesterone

Progesterone is almost absent from the plasma in the early stages of the menstrual cycle. At the time of ovulation, there is a steep rise, and a maximum value is achieved around the 20th–22nd day. Thereafter, a steep fall occurs.

Endometrial cycle

Early Proliferative Phase

The endometrium shows proliferation of its stroma and glands, the latter elongating. The cells lining the glands are cuboidal, with definite limiting membranes, and the stromal cells are thin and spindly.

Late Proliferative Phase

The glands are very large and dilated – late proliferative phase. The blood vessels are also more prominent, and capillaries are dilated.

These proliferative changes are due to the influence of oestrogen secreted by the ovary at this time.

Secretory Phase

Following ovulation, the corpus luteum produces large quantities of progesterone, which induce secretory changes in the glands and swelling of the stromal cells. There is a rich blood supply, and the capillaries become sinusoidal.

Menstruation

Towards the end of the 28-day cycle, the stroma becomes even more vascular and oedematous, small haemorrhages and thrombi appear, and the endometrium ultimately breaks down due to withdrawal of the hormonal support. Vessel necrosis is preceded by intense vasospasm, possibly stimulated by prostaglandin F2-α.

The superficial layers of endometrium, together with blood and leucocytes, are shed and discharged – menstruation. Within a day or two, the raw surface is healed over by epithelium proliferating from the basal portions of glands.

Action of ovarian hormones

Oestrogen

Oestrogens have multiple effects including stimulation of growth and development of secondary sex features in the female.

Progesterone

This hormone prepares the endometrium for implantation of the fertilised ovum and has no homologue in the male. In a clinical sense, it has an antioestrogen action.

Target tissues

	Tissues of these structures are particularly sensitive to oestrogen stimulation. The cytoplasm of their cells contains a specific oestrogen receptor molecule that has an affinity for oestrogen 100,000 times greater than the carrier protein, which retains the hormone in the bloodstream. Oestrogen also acts at the cell membrane, regulating ligand-gated ion channels.
	Progesterone receptors appear in the cytoplasm only after the cell has been primed by oestrogen.

Transfer of the oestrogen molecule to the cell nucleus occurs more readily during the FSH phase of the cycle than during the LH phase, when progesterone levels are the highest. The number of oestrogen receptors is reduced after the menopause, but they never disappear.

The steroids, being lipids, are transported by quite separate lipophilic proteins, and the tissues stimulated by the steroids have their receptors in the cell cytoplasm, instead of on the cell surface as in the preceding steps of the ovulatory process.

Effects of ovarian hormones

Genital tract

Oestrogen stimulates growth and vascularisation, while progesterone increases endometrial gland secretion. In the cervix, secretion is considerably increased by oestrogen (to produce a favourable medium for spermatozoa), while progesterone reduces this. In the vagina, oestrogen causes cornification of cells and enlargement of nuclei, with increased deposits of glycogen.

‘Ferning’ pattern in vaginal smear due to oestrogen stimulation.

Breast

Oestrogen stimulates growth of the stroma, duct system and pigmentation, while cyclical progesterone stimulates growth of gland alveoli. Secondary sexual characteristics are controlled by oestrogen.

Hypothalamus

The hypothalamic–pituitary axis mediates the effects of ovarian hormones and controls the menstrual cycle through FSH and LH.

Cardiovascular system

Oestrogen and progesterone have a number of different effects on the vascular tree, including effects on endothelial function, lipid profile and clotting factors.

Skeleton

Oestrogen is an antiresorptive agent that helps to retain calcium in the bones; at puberty, it causes the growth spurt and then the closure of long bone epiphyses.

Psychological characteristics

Mood may fluctuate with the menstrual cycle. Some women experience adverse psychological and physical symptoms premenstrually, termed premenstrual syndrome (PMS) or premenstrual tension (PMT).

Puberty

Puberty is the period of rapid growth when the child develops the physical characteristics of the adult. In addition to growth in stature, enlargement and changes in the function of reproductive organs occur. The mechanisms are poorly understood, but the main feature is an awakening of centres in the hypothalamus, with an increase in the pulsatile release of GnRH, leading to secretion of gonadotrophins. The reason for the absence of pulsatile GnRH secretion in infancy is not known.

The menopause

Menopause is the name given to the stage in life when the woman gradually loses her cyclical ovarian activity. In many ways, it is a reversal of the changes occurring at puberty. It usually takes place between the ages of 47 and 52 and is termed premature if it occurs before 45.

Menstruation rarely ceases abruptly but tends to become somewhat irregular and less frequent over a year or a little longer. The cessation does not appear to be due to a complete disappearance of ovarian follicles. Primordial follicles have been found in the ovaries of postmenopausal women. It would appear that there has to be a critical number of actively growing follicles before the menstrual cycle can operate.

For details of the pathophysiology and clinical features etc. of the menopause, see Chapter 18.

Related

Gynaecology Illustrated