From HPO Axis To Ovulation

HPO Axis 

Throughout a fetus's life, the hypothalamic-pituitary-ovarian (HPO) axis is active. In four to five weeks, the anterior pituitary develops. By ten weeks, the hypothalamus begins to recognize GnRH. The female fetus begins to produce FSH and LH around 10–13 weeks and reaches its peak at 28 weeks.

Following that, these levels start to drop. Maternal steroids, which are progesterone and estrogen, are also secreted by the placenta.The fall in FSH and LH levels in the female fetus is caused by maternal steroids creating a negative feedback loop to the female fetus's HPO axis.

 The gonadotropin (GN) released by the hypothalamus-pituitary axis is not necessary for the development of follicles and the main oocyte stage during foetal life. Growth factors that are being produced in the ovarian cells of the developing oocytes are responsible for that development.  The formation of primordial follicles and oocyte differentiation do not depend on fetal pituitary gonadotropins.

Gonadotropins regulate the various stages of follicular development during the reproductive lifespan. The withdrawal from placental steroids occurs after the fetus is born, when the mother's circulating steroids are removed. The newborn's gonadotropin levels will rise as a result of the removal of negative feedback.  Mild vaginal bleeding that stops on its own may occur in newborn girls; this is caused by withdrawal.

There is some endometrial expansion while the ovaries are still in the early stages of follicular development because they are producing some estrogen.  The gonadotropin surge may cause ovarian cysts in newborns and neonates, as well as some degree of follicular maturation in the fetus. A newborn's abdominal bulk may be the result of enlarged ovarian cysts.

LH and FSH levels rise during the neonatal period, but they swiftly recover to prepubertal (childhood) levels in a year or two. Children won't change till they reach adolescence. There is an increase in gonadotropin levels during puberty. The HPO axis is awakened during childhood after going inactive.

Throughout the reproductive lifespan, gonadotropin levels are varied (hormonal levels change across the menstrual cycle), and folicle growth is cyclical. • Estrogen insufficiency brought on by the loss of ovarian follicles during menopause increases gonadotropin levels and generates positive feedback in the HPO axis.

HPO Axis During Childhood 

The hypothalamus receives inhibitory signals from the central nervous system known as central CNS inhibitors, which is why the hypothalamus is dormant. These brain-based neurotransmitters suppress the anterior pituitary as well as the hypothalamus, causing the pulsatile secretion to be exceedingly sluggish and irregular.

The low concentration of circulating steroids is another factor contributing to the dormancy of the HPO axis. The hypothalamus receives extremely strong negative input as a result of these.This does not imply that gonadotropin-independent follicular development is not occurring.

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HPO Axis During Puberty 

Neurotransmitters that are inhibitory decrease while those that are stimulatory rise. This has an effect on the pulse generator.
  In the absence of estrogen, the neurotransmitters GABA and NPY are inhibitory..  Glutamate, KISSPEPTIN, and neurokinin B are stimulatory neurotransmitters.  There has been an increase in GnRH's pulsatile release.  Pituitary gonadotropins are activated, resulting in the production of FSH and LH; pulsatile secretion will begin slowly and increase in pace later.

First to rise is FSH, then LH. Later, there will be changes during the day.  First, there is a pulsatile, nocturnal release of LH, which is secreted greater than FSH. Follicle formation and estrogen release result from this. Changes in the production of estrogen cause puberty. The feedback systems that are required for menstrual cycles and will eventually appear are essential for cyclic ovulation.  Cycles of anovulation occur.

Stage Of Follicular Formation 

The original oocyte and the flattened pre-granulosa cells are the components of the primordial follicles. This phase begins between weeks 18 and 20 of pregnancy.The oocyte can only survive inside the follicular. The primary oocytes will not survive if an encasing is not formed.

A woman's capacity to produce eggs is set at birth. When the reproductive stage appears, the population has drastically decreased from its initial high.  Deadline: Six weeks is when oogenesis begins. The greatest amount of oogonia (7 million) can be attained at 20 weeks.

Greenline: oocyte development begins at 12 weeks. At eighteen weeks, follicular development begins. At birth, there are only roughly 2 million oocytes left. Childhood experiences atherosia as well. There are still 4 lakh primary oocytes after they reach adolescence.

 When puberty begins, the menstrual cycle begins. During follicular growth, one follicle will become the dominant ovulating follicle. Every month, a large number of follicles—roughly 1000—perish as the dominant follicle ovulates. During adolescence, about 400 primary oocytes ovulate; the remaining ones die.

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Follicular Growth 

 The primary oocyte is located in the heart of the primordial follicle. A layer of granulosa cells covers the basement membrane.  Within the primary follicle, there is a single layer of cuboidal granulosa cells. The zona pellucida is the name of the protective coating secreted by the oocyte. This is the first area where FSH receptors become visible.

 There are multiple layers of granulosa cells in the secondary follicle. The follicle itself is also larger. The layer of theca cells has also started to form.There are an increasing number of FSH and LH receptors in the body. The Theca layer undergoes vascularization, and LDL cholesterol from the bloodstream enters the Theca cells to be used in hormone production. Because the granulosa layer is avascular, the androgens produced in the theca cells diffuse to it. The call-exner bodies, which are empty gaps, divide the granulosa cells.

 A tertiary follicle that is significantly larger. It is believed that the empty cavities seen in the secondary follicle combine to form the antral cavity known as the antrum. The antrum is filled with material secreted by the granulosa cells. There are more LH and FSH receptors as well as increased vascularity.

Additionally, a distinct external and internal theca layer emerges.The Graafian follicle, sometimes referred to as the preovulatory follicle, emerges subsequent to the tertiary follicle.
Pre-antral follicles are primordial, primary, and secondary follicles. The oocytes' local growth factors give rise to the late pre-antral stage, which is independent of GN.

tertiary and graafian antral follicles. The GN is required for this step.  The process of developing primordial follicles into preovulatory follicles takes 85 days.  The follicular phase of the menstrual cycle is when greater growth occurs when follicles are ready to react to FSH and LH. Most follicle growth happens in the GN-independent stage; only a part is completed during the menstrual cycle.

Ovulation

 Ovulation is more than just the release of the egg; there are gap connections between the granulosa cells and the oocyte membrane. Oocytes secrete growth factors required for granulosa proliferation, while granulosa cells secrete chemicals known as oocyte maturation inhibitors (OMIs) to halt meiosis. There is two-way communication here.

Ovulation is triggered by a rise in LH. The communication breaks down as a result of the gap junctions breaking. The OMIs are no longer given to the oocytes. Here we start meiosis 1.

 The LH surge also increases prostaglandins such PGE2 and local proteases produced in the follicles. This results in the disruption of the follicular wall and the progressive release of the secondary oocyte. Instead of exploding during ovulation, the oocyte slowly expels itself.

Corpus Luteum 

 Luteinized granulosa cells are filled with lipid-rich granules that give it a yellow hue; there is a collapsed antrum full of fibroids and clots; the corpus luteum develops from whatever is left over after ovulation. They are cytoplasmic vacuoles containing lipid-rich granules. There is also a layer of luteinized theca.

Additionally, there is vascularity in the granulosa cell layer.The corpus luteum has a highly vascularized structure. The basement membrane of the granulosa cells is punctured by vascular supply. This is how the LDL cholesterol enters the luteinized granulosa cells. Progesterone levels rise during the luteal phase of the cycle as a direct result of LDL cholesterol entering the cells.

Ovarian Cycle 

The follicular phase of the cycle, during which FSH promotes follicle creation. Ultimately, LH facilitates maturation and is also essential for complete follicular genesis.  During the luteal phase of the cycle, when the secondary oocyte is expelled, the corpus luteum stays behind. LH is also responsible for ovulation and helps to resume meiosis.

It produces estrogen and progesterone. Until it naturally dies, the corpus luteum is kept alive by the LH hormone.  The hormones released throughout the ovarian cycle alter the uterine endometrial lining; this results in the development of corpus albicans, which causes progesterone to be withdrawn, initiating a new cycle.

The cycle starts when the menstrual starts. During the follicular phase, the hormone estradiol is secreted, which leads to proliferative changes in the endometrium. Day 14 is when ovulation occurs. The luteal phase begins. The corpus luteum undergoes luteolysis and has a lifespan of roughly 10–12 days when there is no pregnancy. The corpus luteum secretes progesterone, which raises progesterone levels and secretory endometrium. Endothelin, PGF2α, and nitric oxide are factors that cause lipolysis. If progesterone and estradiol are halted, menstruation will follow.

Hope you found this blog helpful for your Basic Sciences OBS-GYN preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.