What are the two key functions of the ovary?
1) Generation of a fertilizable oocyte with full competence
2) Secretion of steroid hormones required for preparation of the reproductive tract for fertilization and subsequent establishment of pregnancy
Describe what is seen in this ovarian cortex
There are four main types of follicles:
Premordial follicles- consisting of a small primary oocyte with very little cytoplasm surrounded by flat granulosa cells
Primary follicles- which are the next step formed from the premordial follicles (via lack of AMH inhibition from other secondary follicles) and still consist of a single oocyte and a layer of cuboidal granulosa cells, but the cytoplasm is larger
Secondary follicles- more granulosa layers (from 2-100 layers)(the main producer of AMH to feedback inhibit on premordial follicles)
Tertiary follicles- marked by accumulation of fluid as more estrogen is made by the oocyte (begin to produce more estradiol than AMH)
What happens once all premordial follicles are depleted?
Describe the development of the dominant follicle during a menstrual cycle
The primary role of the follicle is oocyte support. From birth, the ovaries of the human female contain a number of immature, primordial follicles. These follicles each contain a similarly immature primary oocyte. After puberty and commencing with the first menstruation, a clutch of follicles begins folliculogenesis, entering a growth pattern that will end in death or in ovulation (the process where the oocyte leaves the follicle).
During post-pubescent follicular development, and over the course of roughly a year, primordial follicles that have begun development undergo a series of critical changes in character, both histologically and hormonally. Two-thirds of the way through this process, the follicles have transitioned to tertiary, or antral, follicles. At this stage in development, they become dependent on hormones emanating from the host body, causing a substantial increase in their growth rate.
With a little more than ten days until the end of the period of follicular development, most of the original group of follicles have died (a process known as atresia). The remaining cohort of follicles enter the menstrual cycle, competing with each other until only one follicle is left. This remaining follicle, the late tertiary or pre-ovulatory follicle, ruptures and discharges the oocyte (that has since grown into a secondary oocyte), ending folliculogenesis.
What are the two key functions of the endometrium?
1. Cyclic regeneration and secretion of substances that foster fertilization and implanation
2. Development of vascular support and immunitary protection for establishment and progression of pregnancy
What causes the endometrium to grow during the follicular phase?
FSH stimulates the follicular growth and more estrogen production which causes endometrium growth until ovulation.
After ovulation, the anterior pituitary begins producing more LH which promotes progesterone production for the luteal phase of the menstrual cycle
What causes the variation in the menstrual cycle in women?
While the luteal phase is typically fixed at a 14 day length, the follicular phase varies from 14-21 days and accounts for the change
What happens to the menstrual cycle around age 40?
There begins to be less and less follicles so estrogen is decreased and the brain senses this and tells the pituitary to produce more FSH causing ovulation to occur more quickly and cycles to be shorter
FSH and LH levels skyrocket in peri/post-menopausal women!
What happens after a few years of shorter cycles?
The ovaries begin to decrease less follicles and responds less and less to FSH leading to longer cycles and eventually the disappearance of periods
Give an overview of the follicular phase of menstruation
At puberty, the follicular phase begins with GnRH being released from the hypothalamus due to release of negative feedback effects of progesterone from the previous luteal phase and causes secretion of FSH that stimulates folliculogenesis and estradiol production, leading to progressive growth of the follicles selected during that cycle.
This increase in estradiol production slowly rises then feeds back negatively on the hypothalamus, resulting in suppression of FSH (and LH). Similarly, tertary follicles secrete Inhibin B which inhibits FSH production. Thus, FSH levels fall as the follicle matures (after about 7-8 days). Before FSH levels drop, a dominant follicle is selected via FSH upregulating LH receptors on its surface and AMH causing agenesis of all others.
Near ovulation, there is an abrupt shift from negative feedback to positive feedback of estrogen (near at least 200pg for 2 days to promote LH surge), causing a surge of LH (and FSH) that stimulates ovulation. The frequency of LH pulses continues to be approx. 1/hr, but the amplitude of the LH pulses increases dramatically
How would the follicular phase be different in older women?
She will have lower production of Inhibin B during the follicular phase due a lower number of follicles, as well as estrogen being produced at a much faster pace
What is Day 1 of the menstrual cycle?
The first day of menses, when the follicular phase begins again and FSH begins to rise (until day 7-8 usually)
What does the surge in LH cause in the oocyte?
The oocyte, which is tetraploid (4n, 96), will be stimulated to finish meiosis I and lose the polar body before arresting again in metaphase of meiosis II before ovulation
What happens in the luteal phase of menstruation?
Progesterone conc. rise in the middle to late luteal phase and LH pulses slow to 1 pulse every 4 hrs and pulses of progesterone occur soon after these. Progesterone works to stabilize the endormetrium in case pregnancy occurs
T or F. Inhibin A levels peak in the mid-luteal phase
T. While Inhibin B secretion is virtually absent during the luteal phase
Serum leptin conc are highest in the ______ phase
What causes Menses?
The decline in estradiol and progesterone release from the corpus luteum results in the loss of endometrial blood supply, endometrial sloughing, and the onset of menese approx. 14 days after ovulation.
In response to falling corpus luteum steroud production, the HPO axis resets and FSH levels begin to rise again
What is Polycystic Ovary Syndrome?
When there are 12+ follicles in an ovary (counted via ultrasound) accompanied with increased production of androgens leading to anovulation and hirsutism typically. There is not enough estrogen to induce ovulation is these circumstances
How much LH is needed for ovulation?
At day three when LH levels are the lowest, the levels are 6-7milliunits/ml, and at the time of the surge it will rise to about 70 milliunits/ml
Why would you check basal body temp if you suspected a women wasnt ovulating?
the body temp increases after ovulation due to progesterone
What is the best time to measure serum progesterone to check if ovulation occured or not?
What would an elevated Day 3 FSH suggest?
the brain is telling the ovaries to produce more estrogen, i.e. in older women
T or F. Regardless of the cycle length, ovulation typically occurs 14 days prior to menses
T. The luteal phase length is fixed at 14 days
What happens to cervical mucus at ovulation?
It increases in quantity and becomes watery and more penetrable by sperm
How does the high level of progesterone secreted from the corpus luteum affect the endometrium?
It makes it more vascular to facilitate receving an ovum. (While in the follicular phase, estradiol makes the endormetrium proliferate)
Why does the temperature of the body increase during the luteal phase?
Progesterone increases the hypothalamic temp set-point
Why do the levels of progesterone and estradiol fall sharply during menses?
Their main source, the corpus luteum, regresses
How long does menses typically last?
Describe development of a premordial follicle
Starting about 18-22 after conception, the cortex of the female ovary contains its peak number of follicles (about 4 to 5 million in the average case, but individual peak populations range from 6 to 7 million 'These primordial follicles contain immature primary oocytes surrounded by flat, squamous granulosa cells (the support cells) that are segregated from the oocyte's environment by the basal lamina. They are quiescent, showing little to no biological activity.
The supply of follicles decreases slightly before birth, and to 180,000 by puberty for the average case (populations at puberty range from 25,000 to 1.5 million). By virtue of the "inefficient" nature of folliculogenesis (discussed later), only 400 of these follicles will ever reach the preovulatory stage
What causes formation of a primary follicle at puberty?
The granulosa cells of these primordial follicles change from a flat to a cuboidal structure (due to lack of AMH inhibition?), marking the beginning of the primary follicle. The oocyte genome is activated and genes become transcribed. Rudimentary paracrine signalling pathways that are vital for communication between the follicle and oocyte are formed. Both the oocyte and the follicle grow dramatically, increasing to almost 0.1 mm in diameter.
granulosa cells in the primary follicles develop receptors to follicle stimulating hormone (FSH) at this time, but they are gonadotropin-independent until the antral stage. Research has shown, however, that the presence of FSH accelerates follicle growth in vitro.
What else happens to the primary follicle?
A glycoprotein polymer capsule called the zona pellucida forms around the oocyte, separating it from the surrounding granulosa cells. The zona pellucida, which remains with the oocyte after ovulation, contains enzymes that catalyze with sperm to allow penetration.
Describe development of a secondary follicle
Stroma-like theca cells are recruited by oocyte-secreted signals. They surround the follicle's outermost layer, the basal lamina, and undergo cytodifferentiation to become the theca externa and theca interna. An intricate network of capillary vessels forms between these two thecal layers and begins to circulate blood to and from the follicle.
The late-term secondary follicle is marked histologically by a fully grown oocyte surrounded by a zona pellucida, approximately nine layers of granulosa cells, a basal lamina, a theca interna, a capillary net, and a theca externa (in that order)
What happens to the follicle in the early tertiary phase?
Granulosa and theca cells continue to undergo mitotis concomitant with an increase in antrum volume. Tertiary follicles can attain a tremendous size that is hampered only by the availability of FSH, which it is now dependent on. The corona radiata then forms from granulosa cells.
Theca cells express receptors for luteinizing hormone (LH). LH induces the production of androgens by the theca cells, most notably androstendione, which are aromatized by granulosa cells to produce estrogens, primarily estradiol. Consequently, estrogen levels begin to rise.
This rise in estrogen begins to cause proliferation of the endometrium during the later part of the follilcular phase
Late tertiary phase
At this point, the majority of the group of follicles that started growth 360 days ago have already died. This process of follicle death is known as atresia, and it is characterized by radical apoptosis of all constituent cells and the oocyte. Although it is not known what causes atresia, the presence of high concentrations of FSH has been shown to prevent it.
A rise in pituitary FSH caused by the disintegration of the corpus luteum at the conclusion of the previous menstrual cycle (lack of neg feedback) precipitates the selection of five to seven class 5 follicles to participate in the next. The selected follicles, called antral follicles, compete with each other for growth-inducing FSH.
In response to the rise of FSH, the antral follicles begin to secrete estrogen and inhibin, which have a negative feedback effect on FSH. Follicles that have fewer FSH-receptors will not be able to develop further; they will show retardation of their growth rate and become atretic. Eventually, only one follicle will be viable. This remaining follicle, called the dominant follicle, will grow quickly and dramatically—up to 20 mm in diameter—to become the preovulatory follicle.
Note: Many sources misrepresent the pace of follicle growth, some even suggesting that it takes only fourteen days for a primordial follicle to become preovulatory. Actually, the follicular phase of the menstrual cycle means the time between selection of a tertiary follicle and its subsequent growth into a preovulatory follicle.The actual time for development of a follicle is varied among cases.
What type of oocyte is ovulated?
a secondary oocyte suspended in metasphase of meiosis II
T or F. only antral follicles are dependent on FSH and LH).
GnRH stimulates the release of FSH and LH from the anterior pituitary gland that will later have a stimulatory effect on follicle growth (not immediately, however, because only antral follicles are dependent on FSH and LH). When theca cells form in the tertiary follicle the amount of estrogen increases sharply (theca-derived androgen is aromatized into estrogen by the granulosa cells).
At low concentration, estrogen inhibits gonadotropins, but high concentration of estrogen stimulates them. In addition, as more estrogen is secreted, more LH receptors are made by the theca cells, inciting theca cells to create more androgen that will become estrogen downstream. This positive feedback loop causes LH to spike sharply, and it is this spike that causes ovulation.
Following ovulation, LH stimulates the formation of the corpus luteum. Estrogen has since dropped to negative stimulatory levels after ovulation due to degeneration of granulosa cells and therefore serves to promote lower concentration of FSH and LH throughout the initial luteal phase. Inhibin, which is also secreted by the corpus luteum, contributes to FSH inhibition.
What is Mittelschmerz?
When blood from a ruptured follicle cause periotneal irritation that can mimic appendicitis
What is oligomenorrhea?
35+ day cycle
What is polymenorrhea?
less than a 21 day cycle
What is metrorrhagia?
frequent but irregular menstruation
What is menometrorrhagia?
heavy, irregular menstruation at irregular intervals