Menstrual Cycle

Question 1

What are the two key functions of the ovary?

Answer 1

1) Generation of a fertilizable oocyte with full competence2) Secretion of steroid hormones required for preparation of the reproductive tract for fertilization and subsequent establishment of pregnancy

Question 2

Describe what is seen in this ovarian cortex

Answer 2

There are four main types of follicles:Premordial follicles- consisting of a small primary oocyte with very little cytoplasm surrounded by flat granulosa cellsPrimary follicles- which are the next step formed fromthe 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 largerSecondary 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)

Question 3

What happens once all premordial follicles are depleted?

Answer 3

Menopause

Question 4

Describe the development of the dominant follicle during a menstrual cycle

Answer 4

The primary role of the follicle isoocytesupport. From birth, theovariesof the human female contain a number of immature,primordial follicles. These follicles each contain a similarly immatureprimary oocyte. Afterpubertyand commencing with the firstmenstruation, 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 totertiary, 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 themenstrual 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 asecondary oocyte), ending folliculogenesis.

Question 5

What are the two key functions of the endometrium?

Answer 5

1. Cyclic regeneration and secretion of substances that foster fertilization and implanation2. Development of vascular support and immunitary protection for establishment and progression of pregnancy

Question 6

What causes the endometrium to grow during the follicular phase?

Answer 6

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

Question 7

What causes thevariation in the menstrual cycle in women?

Answer 7

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

Question 8

What happens to the menstrual cycle around age 40?

Answer 8

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 shorterFSH and LH levels skyrocket in peri/post-menopausal women!

Question 9

What happens after a few years of shorter cycles?

Answer 9

The ovaries begin to decrease less follicles and responds less and less to FSH leading to longer cycles and eventually the disappearance of periods

Question 10

Give an overview of the follicular phase of menstruation

Answer 10

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.Thisincrease in estradiol production slowly rises thenfeeds 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

Question 11

How would the follicular phase be different in older women?

Answer 11

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

Question 12

What is Day 1 of the menstrual cycle?

Answer 12

The first day of menses, when the follicular phase begins again and FSH begins to rise (until day 7-8 usually)

Question 13

What does the surge in LH cause in the oocyte?

Answer 13

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

Question 14

What happens in the luteal phase of menstruation?

Answer 14

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

Question 15

T or F. Inhibin A levels peak in the mid-luteal phase

Answer 15

T. While Inhibin B secretion is virtually absent during the luteal phase

Question 16

Serum leptin conc are highest in the ______ phase

Answer 16

luteal

Question 17

What causes Menses?

Answer 17

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

Question 18

What is Polycystic Ovary Syndrome?

Answer 18

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

Question 19

How much LH is needed for ovulation?

Answer 19

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

Question 20

Why would you check basal body temp if you suspected a women wasnt ovulating?

Answer 20

the body temp increases after ovulation due to progesterone

Question 21

What is the best time to measure serum progesterone to check if ovulation occured or not?

Answer 21

Day 21

Question 22

What would an elevated Day 3 FSH suggest?

Answer 22

the brain is telling the ovaries to produce more estrogen, i.e. in older women

Question 23

T or F. Regardless of the cycle length, ovulation typically occurs 14 days prior to menses

Answer 23

T. The luteal phase length is fixed at 14 days

Question 24

What happens to cervical mucus at ovulation?

Answer 24

It increases in quantity and becomes watery and more penetrable by sperm

Question 25

How does the high level of progesterone secreted from the corpus luteum affect the endometrium?

Answer 25

It makes it more vascular to facilitate receving an ovum. (While in the follicular phase, estradiol makes the endormetrium proliferate)

Question 26

Why does the temperature of the body increase during the luteal phase?

Answer 26

Progesterone increases the hypothalamic temp set-point

Question 27

Why do the levels of progesterone and estradiol fall sharply during menses?

Answer 27

Their main source, the corpus luteum, regresses

Question 28

How long does menses typically last?

Answer 28

4-5 days

Question 29

Describe development of a premordial follicle

Answer 29

Starting about 18-22 afterconception, the cortex of the femaleovarycontains its peak number of follicles (about 4 to 5 million in the average case, but individual peak populations range from 6 to 7 million’Theseprimordial folliclescontain immature primary oocytes surrounded by flat, squamousgranulosa cells(the support cells) that are segregated from the oocyte’s environment by the basal lamina. They are quiescent, showing little to nobiological 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).[3]By virtue of the “inefficient” nature of folliculogenesis (discussed later), only 400 of these follicles will ever reach the preovulatory stage

Question 30

What causes formation of a primary follicle at puberty?

Answer 30

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 theprimary follicle. The oocyte genome is activated and genes becometranscribed. 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 0.1mm in diameter.granulosa cells in the primary follicles develop receptors tofollicle 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 growthin vitro.

Question 31

What else happens to the primary follicle?

Answer 31

A glycoprotein polymer capsule called thezona pellucidaforms around the oocyte, separating it from the surrounding granulosa cells. The zona pellucida, which remains with the oocyte after ovulation, contains enzymes that catalyze withspermto allow penetration.

Question 32

Describe development of a secondaryfollicle

Answer 32

Stroma-like theca cells are recruited by oocyte-secreted signals. They surround the follicle’s outermost layer, thebasal lamina, and undergo cytodifferentiation to become thetheca externaandtheca 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)

Question 33

What happens to the follicle in the early tertiary phase?

Answer 33

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 radiatathen forms from granulosa cells.Theca cells express receptors for luteinizing hormone (LH). LH induces the production ofandrogensby the theca cells, most notablyandrostendione, which are aromatized by granulosa cells to produceestrogens, primarilyestradiol. 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

Question 34

Late tertiary phase

Answer 34

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 asatresia, and it is characterized by radicalapoptosisof 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 andinhibin, which have a negative feedback effect on FSH.Follicles that have fewerFSH-receptorswill 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 thedominant follicle, will grow quickly and dramatically—up to 20mm in diameter—to become thepreovulatory 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.

Question 35

What type of oocyte is ovulated?

Answer 35

a secondary oocyte suspended in metasphase of meiosis II

Question 36

T or F. only antral follicles are dependent on FSH and LH).

Answer 36

T

Question 37

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.

Question 38

Luteal phase

Answer 38

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 cellsand therefore serves to promotelower concentration of FSH and LH throughout the initial luteal phase. Inhibin, which is also secreted by the corpus luteum, contributes to FSH inhibition.

Question 39

What is Mittelschmerz?

Answer 39

When blood from a ruptured follicle cause periotneal irritation that can mimic appendicitis

Question 40

What is oligomenorrhea?

Answer 40

35+ day cycle

Question 41

What is polymenorrhea?

Answer 41

less than a 21 day cycle

Question 42

What is metrorrhagia?

Answer 42

frequent but irregular menstruation

Question 43

What is menometrorrhagia?

Answer 43

heavy, irregular menstruation at irregular intervals