#13360 - Menstrual Cycle Essay - Organisation of the Body

Write an essay on the hormonal control of the menstrual cycle. What occurs in the uterine and ovarian cycles?

The menstrual cycle which begins at puberty and ends at menopause, describes the cyclic changes in the uterus and the ovary. The main function of the ovary is to produce a haploid oocyte whilst the main function of the uterus is to accept the fertilized ovum which then impants into the endometrium and receives nourishment from blood vessles of the uterus. In humans, the menstrual cycle lasts 28 days and is determined by follicle growth and the corpus luteum lifespan. The ovarian cycle has two distinct phases; in the follicular phase, oocyte and its surrounding follicle mature and ends with the oocyte being ovulated, in the luteal phase, the remaining follicle develops into an endocrine corpus luteum and if there is no implantation there is sloughing of the uterine endometrium and involution of the corpus luteum into a corpus albicans. In regards to the uterus, the main stages are menstruation, proliferative and secretory phase.

Structure of the ovary

The cyclic nature of the menstrual cycle was reflected in the ovarian cycles which was seen when an ovary is inspected under a microscope. The outercortex of the ovary has germ cells within follicles that are at different stages of development. Each of these follicles contains a primary oocyte, surrounded by zona pellucida and a variable number of granulose cells depending on what stage of development they are at. During late stages of development there are also thecal cells surrounding the granulosa cells. Between the follicles, the stroma contains corpora lutea, which is a temporary endocrine structure that secretes high levels of progesterone and moderate levels of estradiol and inhibin A. If there is no implantation the corpous luteus is broken down by macrophages and is replaced by type 1 collagen formed by fibroblasts; this forms the corpus albicans.

The inner medulla of the ovary conists of vessels, nerves and steroid secreting cells.

Formation of primary follicles

During fetal development there are a pool of stem cells called oogonia which increase by proliferation. Unlike in males, meiosis starts during fetal development but is arrested in prophase of meiosis 1 to form a primary oocyte. The nuclei in these cells are large and watery which is essential as it protects the DNA which remains dormant for long periods of time. The primary oocyte then enlarges and granulose cells, derived from the surrounding stroma, form a single layered follicular epithelium to form the primordial follicle. The primordial follicle then develops into the primary follicle where the oocyte has greatly enlarged and the follicular cells have multiplied by mitosis and become cuboidal in shape. At this stage, thick layer of glycoprotein is formed by the secretion of both the oocyte and follicular cells and lies between the two. The surrounding stromal cells form an organised layer around follicles called the theca folliculi and are separated from the granulosa cells by a basemement membrane. The basemement membrane ensures no blood vessels penetrate. A key germ cell transcription factor that is essential in the formation of the primary follicles is GDF-9 as knockout of these genes results in the presence of large follicles with only single layer of granulosa cells and mature follicles don’t develop. Development of the primary follicle is gonadotrophin independent and few follicles start development process every few days and by 5 months the number of primordial follicles in the ovaries peak at 7 million but undergo atresia so by puberty 400,000 follicles remain.

Endocrine control of the menstrual cycle

The stages following the primary follicle and the initiation of the menstrual cycle occurs at puberty where there are monthly cycles in the secretion of hypothalamic, pituitary and ovarian hormones which result in the production of a female gamete and a uterus primed to receive fertilised embryo. The two main hormones that are essential in the ovarian and uterine cycles are by LH and FSH which are glycoprotein hormones that are secreted by the gonadoroph cells in the anterior pituitary. This was discovered when hypophysectomy caused gonadal atrophy and consequently loss of the menstrual cycle. But when extracts of LH and FSH were injected the gonadal function was restored. LH and FSH are released in response to gonadotrophin releasing hormone secreted by the hypothalamus. GnRH is released in pulses every 90 minutes which enter the portal veins. The key evidence that proves the anterior pituitary is under control of the hypothalamus was shown when the pituitary was repositioned under the kidney capsule and this resulted in infertility but when replaced under the pituitary fossa it restored the oestrous cycle. Knock out of the gonadotrophin hormone also resulted in a loss of gonadal activity.

Follicular stage of the menstrual cycle

1) Maturation of the follicle

At the beginning of the menstrual cycle, the FSH secreted by the anterior pituitary binds to FSH receptors on the granulosa cells. FSH plays a key role in the development of the follicles and is shown when knock out of either the FSH gene or FSH receptor results in follicles that don’t mature and remain as primary follicles. Once puberty has begun the primary follicles develop into secondary follicles FSH induce further proliferation of the granulosa cells and differentiation of the thecal follicular cells into two layers; theca interna and external. The thecal layers become highly vascularised unlike the granulosa layers and this is shown using carbon perfusion. The FSH also stimulates the granulosa cells to secrete fluid which coalesce to form an antrum. The large antrum seperates mural granulosa cell lining the basal lamina of the follicle from the cumulus granulosa cells which surround the oocyte and zona pellicuda. This is essential as during ovulation only the cumulus granulosa cells and the primary oocyte are secreted during ovulation.

The FSH also results in the formation of LH receptors on the theca internal cells. The LH acts on the LH receptor on theca interna cells inducing proliferation of the cells and also stimulates the production of androstenedione, which is an androgen. The androgen secreted by thecal cells is converted into oestrogens by the FSH induced aromatase enzymes in the granulosa cells. The FSH also stimulates the granulosa cells to secrete peptide hormones and growth factors. Both the peptides and oestrogen released from the ovary results in a decrease in the FSH secreted due to negative feedback at the level of the pituitary and the hypothalamus.

During the stages between primary to secondary 10 follicles mature simultaneously but at the 14^th day stage of the follicular phase, a dominant preovulatory graffian...