menstrual cycle Flashcards
- Describe oogenesis
Oogonium > primary oocyte > secondary oocyte > if unfertilized, ovulated secondary oocyte degenerates
atresia of female gametes
fetus has 6-7 million oogonia. At birth, 1-2 million primary oocytes remain. At puberty, 400,000 primary oocytes remain. 10-30 mature each month.
compare oogenesis to spermatogenesis
Both undergo mitosis, followed by 2 rounds of meiosis. . Spermatozoa undergo both rounds of meiotic division in approximately 64 days. The same process for oogonia is completed in 12 - 50 years. spermatogenesis yields 4 equivalent, mature gametes whereas oogenesis produces only one
describe meiosis 1
Maternal and paternal homologous chromosomes are duplicated. Genetic recombination occurs when homologous segments of DNA are exchanged btw non-sister chromatids. This occurs during fetal life in females and arrests in prophase 1 (primary oocytes, diploid, 4N). During LH surge before ovulation, meisosis 1 completes, homologous chromosomes separate into 1 secondary oocyte and the first polar body each with haploid number of duplicated chromosomes (2N)
contrast meiosis 1 in spermatogenesis vs oogenesis
males: produces 2 secondary spermatocytes, each with a haploid number (23) of duplicated DNA (2N) Females: produces one secondary oocyte with majority of cytoplasm and first polar body. Both have haploid number of duplicated DNA
Describe meiosis 2
The secondary oocyte arrests in Meiosis II, and is only completed if fertilization occurs. Sister chromatids separate from each other at centromere giving rise to 1 ovum and second polar body, each with haploid complement of non-duplicated DNA (1N).
compare the first and second polar bodies
First polar body: produced from meiosis 1, contains 23 chromosomes with duplicated DNA (2N). Can degenerate or divide again. Second polar body: produced from meiosis 2, contains 23 chromosomes with non-duplicated DNA (1N).
List the phases of menstrual cycle
Ovarian function: follicular phase and luteal phase. Endometrial activity: menstrual phase, proliferative phase and secretory phase
Follicular stages
Preantral follicles: primordial, primary and secondary follicle. Antral follicles: tertiary follicle and graafian follicle. A few follicles reach the antral stage each month but only one dominates and ovulates. After ovulation, the corpus luteum develops and remains functional (if pregnant) for several weeks then regresses to the corpus albicans. In absence of fertilization, regression occurs more quickly.
VEGF function in menstrual cycle
vascular endothelial growth factor (VEGF) is produced by granulosa cells in response to LH. VEGF induced angiogenesis increases blood flow to the developing follicles.
Pair the type of follicle with the oocyte contained within them
Primordial, primary, secondary, tertiary and some graafian follicles contain a primary oocyte. The meiotic division which gives rise to the secondary oocyte occurs in the graafian follicle just before ovulation
Two phases of the dominant follicle
GnRH independent phase (estimated at 70 days) and a GnRH dependent phase (estimated at 15 days)
When are primary follicles selected for further maturation
During the luteal phase of the preceding cycle- 10 to 30 follicles are selected.
primary factor which differentiates the dominant follicle from its cohort
Dominant follicle: more estrogenic microenvironment due to better blood supply increasing FSH delivery. More FSH receptors, greater rate of granulosa cell proliferation, more aromatase activity, more estrogen production. Inhibin rises and combines with estradiol to negatively feedback on FSH secretion. Remaining follicles: more androgenic
Why are the non dominant follicles more androgenic
At high concentrations, weak androgens (androstenedione) are preferentially converted to dihydrotestosterone by 5 alpha reductase rather than to estradiol. DHT inhibits LH receptor formation and aromatase function. The non dominant follicles accumulate androstenedione and eventually regresses
describe structure of primordial follicles
primary oocyte surrounded by a layer of pregranulosa cells which, in turn is surrounded by a basement membrane. Prevents atresia of encapsulated oocytes. Most follicles remain in this state and they are formed by 6 months of life
describe structure of primary follicles
contain a larger primary oocyte surrounded by the zona pellucida, a glycoprotein coat that facilitates sperm attachment and fertilization of secondary oocyte. ). The zona pellucida is surrounded by a single layer of cuboidal granulosa cells and the underlying basement membrane
describe structure of secondary follicles
contains a primary oocyte (120 microns), surrounded by the zona pellucida and several layers of cuboidal granulosa cells, surrounded by the associated basement membrane. The adjacent stromal tissue differentiates into theca cells and the vascular supply to the area increases. The granulosa cells acquire receptors for FSH, androgen, and estrogen and become hormonally active. The theca cells develop LH receptors and begin to synthesize steroids.
describe structure of tertiary follicles
contains a primary oocyte, surrounded by the zona pellucida and the granulosa cell layers. FSH and estradiol cause the granulosa cells to proliferate and also to acquire LH receptors. A fluid filled space develops within the granulosa call layer, known as the antrum. The granulosa cell layer is surrounded by the basement membrane, followed sequentially by the theca interna and theca externa.
describe antral fluid
Composed of plasma exudate and follicular secretions components. Also estradiol, progesterone, androgens, inhibin, activin, FSH and LH. Taken together, these factors play roles in follicular development, ovulation, and modulation of hormonal responses.
Describe structure/ development of graafian follicle
Antrum enlarges, the primary oocyte, its associated zona pellucida, and an inner halo of granulosa cells, known as the corona radiata, become enveloped by antral fluid and are attached to remaining granulosa cells by cumulus oophorus stalk. First meiotic division completes, giving rise to a secondary oocyte and the first polar body. Then cumulus oophorus breaks down leaving the oocyte, zona pellucida and cumulus floating in the follicle
describe ovulation
Ovulation follows the estradiol peak, followed by the LH surge. The extrusion of the oocyte from the surface of the ovary is mediated by the combination of weakening of the follicular wall as the result of collagenase, plasmin, and prostaglandin activity and smooth muscle contractions within the thecal layer of the follicle.
corpus luteum structure
This structure consists of granulosa cells, also known as granulosa - lutein cells, and theca cells, also known as theca - lutein cells. By weight, the corpus luteum is one of the most vascular tissues in the body
Function of corpus luteum
Produces progesterone (high levels) and estrogen due to high levels of gonadotropins arriving here. Also, large amounts of LDL are delivered to granulosa cells which switch from de novo cholesterol synthesis.
Function of progesterone secretion by corpus luteum
In the endometrium, progesterone induces changes in the stratus functionalis which allow for successful implantation of a fertilized ovum.
Life span of corpus luteum
If fertilization does occur, human chorionic gonadotropin (hCG) secreted by the conceptus maintains the corpus luteum and its progesterone secretion fornine weeks until the placenta is able to produce progesterone independently. hCG is structurally similar to LH. In the absence of fertilization and hCG secretion, the corpus luteum has a limited life span and begins to regress approximately 11 days after ovulation. Reduced progesterone causes menstruation. The corpus luteum becomes fibrosed (corpus albicans)
describe the pulsatile nature of th H-P-G axis during the follicular vs luteal phase
Follicular: pulsatile secretion is more frequent but smaller in ampitude. Early, FSH and LH are equal. Increased pulsatility rate occurs just prior to ovulation, causig FSH and LH to reach their peaks. Luteal: Increasing progesterone slows LH pulses to every 3-4hrs. As progesterone falls at the end of this phase, pulse frequency increases and FSH is secreted preferentially over LH.
What affects the biological activity of FSH and LH and when are the most bioactive forms secreted
The biological activity or quality of the FSH and LH secreted varies over the cycle as the result of increased sialic acid content or sialylation. The most bioactive forms of FSH and LH are secreted midcycle
FSH actions on granulosa cells
stimulating the proliferation of granulosa cells, increasing the number of FSH and LH receptors on the granulosa cell, stimulating the aromatization of androgens to estrogens, and producing autocrine – paracrine factors such as activin and inhibin.
Activins actions on granulosa cells and theca cells
In the granulosa cells, activin augments the FSH activities . In the theca cells, activin suppresses androgen production, contributing to the creation of an estrogenic microenvironment.
Inhibins actions
Later in the follicular phase, inhibin enhances LH stimulation of androgen synthesis in the theca, thereby providing more substrate for estrogen synthesis in the granulosa cell. This makes the estrogen peak and subsequent LH surge possible. Inhibin B from granulosa cells suppresses FSH secretion by pituitary to ensure dominance of single follicle
estradiol feedback loops
Estradiol is inhibitory at the hypothalamus and pituitary at most concentrations. The exception is when sustained, high levels of estradiol in the mid-follicular phase convert the negative feedback inhibition of estradiol into a positive feedback mechanism. A surge in LH secretion therefore occurs. This LH surge induces ovulation
How long does the LH surge last
48 hrs
Progesterone feedback loops
Progesterone is stimulatory at lower concentrations (the follicular phase) and inhibitory at higher concentrations (the luteal phase). Progesterone augments the positive feedback response of the pituitary to estrogen in a time and dose-dependent manner. progesterone therefore facilitates the positive feedback response of the pituitary to estradiol midcycle. At high levels, progesterone inhibits folliculogenesis by inhibiting gonadotropin release.
structure of the uterus
The endometrium is a simple columnar epithelium that forms tubular glands. It has three layers: stratum basalis (adjacent to myometrium and doesn’t change during menstrual cycle), stratum spongiosum and stratum compactum (the last two comprise the stratum functionalis which is shed during menstruation)
Blood supply to endometrium
Branches of uterine arteries. Two type: straight arteries feed the stromal layer and donot infiltrate the endometrium very deeply. Spiral arteries pass through basal layer and into the stratum functionalis.
Which arteries supplying the endometrium are hormonally sensitive
spiral arteries- they constrict in response to hormonal shifts causing stratum functionalis to become ischemic and therefore to shed.
proliferative phase of menstrual cycle
In response to ovarian estrogen the endometrial stroma proliferates and becomes thicker and highly vascular. The tubular glands of the stratum compactum which invaginate from the endometrial surface elongate and become progressively more coiled.
Secretory phase of menstrual cycle
in response to the high levels progesterone secreted by the corpus luteum the endometrial glands become more tortuous and the endometrial stroma becomes increasingly edematous. The endometrual glands secrete a substance rich in glycogen which is capable of sustaining a conceptus until placentation can occur
Menstrual phase of menstrual cycle
lasts 5 days. As the corpus luteum degenerates, circulating levels of estrogen and progesterone fall. The spiral arteries feeding the stratus functionalis constrict, leading to endometrial ischemia which leads to shedding of the stratum functionalis.
Components of menstrual effluvium
blood, necrotic epithelium, necrotic stroma, inflammatory cells and fibrin deposits
timing of key events in menstrual cycle
Estradiol peak (day 13) > LH surge (day 14) > completion of meiosis 1 > ovulation (day 15, 10-12 hrs after LH peak) > oocyte transport to ampulla (2-3 minutes) > fertilization in ampulla (day 16-17) > cell division and transport to endometrial cavity (day 18-20) > endometrial receptivity (day 20-24) and implantation (day 20-21)
- Label a diagram of the ovarian/menstrual cycle.
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2 cell theory of gonadal functin in female
theca cells convert cholesterol to androstenedione which is then taken to the granulosa cell where aromatase converts it to estradiol. The granulosa cells can produce progesterone but it has to be taken to theca cells to be converted to androstenedione (b/c granulosa cells lack 17alpha-hydroxylase and 17,20 desmolase activity) then back to granulosa cells to convert to estradiol.
