Menstrual cycle and ovulation Flashcards
when does the oocyte arrest throughout its development?
as a primordial germ cell and prenatally, the oocyte will get to Meiotic arrest in prophase I
- due to elevated levels of cAMP
- large antral follicles gain meiotic competence
- will stay here until the LH surge
- can stay here for 50 years
Meiosis I finishes before ovulation
-polar body 1 extruded
Meiotic arrest (metaphase II) -elevated levels MAPK proteins
Resumption of meiosis II only at fetilization
- rapid degradation of MAPK
- polar body 2 extruded
what are the three phases of the Ovarian Follicle cycle
Follicular phase
Ovulatory phase
Luteal phase
what is the ovarian follicle?
it is the functional unit of the ovary
- performs gametogenic and endocrine functions
- pre-menopausal cycling ovary contains follicular structures at many different stages
Primordial follicle
Primary oocyte arrested in first meiotic prophase where it can remain for 50 years
Surrounded by a single layer of pregranulosa cells
release paracrine factors nor steroids
represents the ovarian reserve of which most will undergo atresia
- 400-500 will defelop and ovulate
- 270,000 will atresia
what is the Primary follicle and how is it different than the primordial follicle
Central primary oocyte
single layer of granulosa cell is taken over as a cuboidal shape
increase in size of follicle due to growth of the primary oocyte
early production of secreted glycoproteins
-ZP1,2,3,4
What is the secondary follicle?
still a primary oocyte surrounded by 3-6 layers of cuboidal granulosa cells
secretion of paracrine factors to induce local stromal cells to differentiate into thecal cells
- inner grandular highly vascular theca interna
- fibrous capsule like theca externa
how does the progression to the secondary follicle occur?
Increased vascularization:
-migration from outer cortex to inner cortex, closer to ovarian vasculature
-follicles release angiogenic factors that induce development of 1-2 arterioles (genertates vascular wreath around the follicle)
- Zona pellucida development
- provides binding site for sperm during fertilization (ZP1-4)
what is the endocrine function of the prenatral follicles
Minimal endocrine function:
-Granulosa cells expresses FSH receptors primarily dependent on paracrine factors from oocyte for growth
-granulosa cells do not produce ovarian hormones at this point
-Thecal cells are analogous to testicular leydig cells
express LH receptors
Major product is androestenedione which is minimal or absent at this point
Antral Follicular Development
The appearance of the antrum marks the beginning of the antral phase
-increase in follicular size depends on the increase in antral size, volume of the follicular fluid, and proliferation of granulosa cells
Oocyte becomes suspended in fluid surrounded by a dense mass of granulosa cells
-Corona radiata/cumulus oophorus
what gonadotropins are responsible for the growth of the antral follicle
Theca interna gets acted on by LH
- synthesize androgens from acetate and cholesterol
- androstenedione is major steroid product
- limited estrogen synthesis
Granulosa cell gets acted on by FSH
- Convert androgens from thecal cells to induce granulosa mediated aromatization of androgens to estrogens
- stimulated by FSH
- makes estradiols and progesterone
how does the Gamete change as the Antral follicle grows
Oocyte grows rapidly in the early stages of antral follicles that the growth will slow in the larger follicles
at the antral stage the oocyte becomes competent to complete meiosis I at ovulation
- oocyte synthesizes sufficient amount of cell cycle components (CDK-1 and Cyclin B)
- Larger antral follicles gain meiotic competence but still maintain meiotic arrest until the midcycle luteinizing hormone LH surge
- Meiotic arrest is achieved by the maintenance of elevated cAMP levels in the mature oocyte
how is the Dominant follicle chosen on the follicular phase and what does this follicle become?
Several large antral follicles are recruited to begin development each monthly cycle
Selection of 1 dominant follicle early in follicular phase
Mural granulosa produce low levels of estrogen and inhibin B
- FSH levels will decline
- Largest follicle with most FSH receptors (highest sensitivity) becomes dominant follicle
- others undergo atresia which is apoptosis of oocytes and granulosa cells
The now midcycle dominant follicle becomes a large preovulatory follicle (graffian follicle)
What happens during the Periovulatory Period
Defined as time from onset of LH surge to ovulation
-32-36 hours
Structural changes begin to prepare for ovulation
Changes in the steroidogenic function of theca and mural granulosa
- prepares cells for luteinization
- formation of corpus luteum
- increased production of progesterone
Luteinization? how does it happen and what happens to the thecal and mural granulosa cells?
LH surge induces differentiation or luteinization of granulosa cells to granulosa lutein cells
Thecal and mural granulosa express LH receptors at the surge that induces shift in steroidogenic activity that leads to transient inhibition of aromatase expression
-rapid decline reduces positive feedback on LH secretion
also increase vascularization of granulosa cells to allow for increase cholesterol availabillity for progesterone production
what are the structural changes induced after luteinization and ovulation? and how does it affect the gamete?
Release of cytokines and hydrolytic enzymes from theca and granulosa cells
-breakdown of follicle wall, tunica albuginea, and surface epithelium
Cumulus oocyte complex detaches making it now free floating in antrum
Basal lamina of mural granulosa degraded
- angiogenic factors released
- increased blood supply to the follicle and soon to be corpus luteum
LH surges induces oocyte to progress to metaphase II
Beginning of the luteal phase and development of Corpus Luteum
Antral cavity of the follicle will fill with blood and cell debris making it the Corpus hemorrhagicum
-these will eventually be removed by marophages
THe granulosa lutein cells will collapse into the antral cavity and be filled with:
- cholesterol esters
- THeca, blood vessels, white blood cells will fill the remainder
now considered Corpus luteum
-often have yellow appearance in color due to caotenoid pigment, lutein
how long does the corpus luteum remain? unless?
Corpus luteum of menstruation remains for 14 days where it will become Corpus albicans which is a scar-like body, and composed of primarily collagen
Unless it is rescued by human chorionic gonadotropin (hCG) from conceptus, and will remain viable for duration of pregnancy
How does the Corpus Luteum impact pregnancy?
Corpus Luteum produces increasing progesterone
-transforms uterine lining into adhesive and supportive structure which is important for implantation and early pregnancy
Transient decrease in estrogen following LH surge, rebounds and peaks midluteal phase
Progesterone and estrogen reduces LH to basal levels
-hCG compensates for this decline
Lutein cells secrete inhibin A and supresses FSH
What is follicular atresia?
Demise of an ovarian follicle
Predominant process in the ovary
Can occur at any time during development
During atresia, the granulosa cells and oocytes undergo apoptosis
Thecal cells persist and repopulate the cellular stroma of the ovary
-retain the LH receptors and the ability to produce androgens, collectively are referred to as the interstitial gland of the ovary
what is the hypothalamic pituitary ovarian axis?
Hypothalamic neurons synthesize, store and release GnRH
GnRH binds to receptors on the gonadotropins in the anterior pituitary that synthesize and release LH and FSH
LH and FSH stimulate the ovary to synthesize and secrete estrogen and progestins
ovaries also produce inhibin and activins
also ovarian steroids and peptides produce both negative and positive feedback on both the hypothalamus and the anterior pituitary
how does GnRH play a role in the LH surge
GnRH is released in rhythmic pulses that early in the follicular phase the gonadotropins are not very sensitive to the GnRH that only release a small amount of LH
later in the follicular phase the gonadotropins in the anterior pituitary are more sensitive that lead to a bigger release of LH
-hence the surge of LH
how does LH and FSH act on the ovarian cell before and after the ovulation
important for the secretion of estrogens and progestins
Before LH and FSH act on the cellsof the developing follicle
- theca cells have LH receptors and granulosa cells have LH and FSH
- Both FSH and LH required for estrogen production because neither theca cells nor granulosa cells can carry out all required steps
After ovulation: LH acts on the cells of the corpus luteum
How do inhibins work?
Ovaries produce inhibins via the granulosa cells
- FSH specifically stimulates the granulosa cell to produce inhibin
- just before ovulation, after the granulosa cells acquire LH receptors, LH stimulates the production of inhibins by granulosa cells
- inhibins inhibit FSH production by the gonadotrophs
what do activins do
produced by the granulosa cell to stimulate the FSH release from the pituitary cells
Negative feedback of estrogens and progestins
Estrogen exert negatve feedback at both low and high oncentrations
progestins are effective only at high concentrations
both net effect is to reduce LH and FSH release
Positive feedback of estrogens and progesterone?
at the end of the follicular phase estradiol levels rise gradually during the 1st half of the follicular phase and steeply during the 2nd half
after the estradiol levels reach a certain threshold, for a minimum of 2 days, HP axis reverses making estrogen exert a positive feedback
-promotes LH surge
rising levels of progesterone during late follicular phase also produces a positive feedback response and thus facilitates the LH surge
as the luteal phase of the cycle begins what happens to the levels of LH and FSH
LH and FSH rapidly decrease
This fall off in gonadotropin levles reflects negative feedback by estradiol, progesterone, and inhibin
as gonadotropin levels fall so do the levels of ovarian steroids
what happens to the levels of estradiol, progesterone, and inhibin in the luteal phase
there is a rise in concentration of estradiol, progesterone, and inhibin thanks to the corpus luteum
-causes a decrease of gonadotropin levels (LH, FSH)
until late luteal phase, the gradual demise of the corpus luteum leads to the now decrease in levels of progesterone and estradiol and inhibin
-this then starts over the menstruation period where LH and FSH begin to increase again
what produces estradiol in the follicular and luteal phase? and what cells are needed in each phase?
in the follicular phae, the follicle synthesizes estrogens where as in the luteal phase the corpus luteum does the synthesis
needs the theca and granulosa cells in the follicle
needs the theca lutein and granulosa lutein cells within the corpus luteum
What is the Hormonal regulation of basal body temperature during the menstrual cycle?
Higher levels of estrogen present during the preovulatory follicular phase of the menstrual cycle leading to a lower BBT
higher levels of progesterone released by the corpus luteum after ovulation raises the BBT
If pregnancy does not occur, disintegration of the corpus luteum causes a drop in BBT that roughly coincides with the onset of the next menstruation
THe endometrial cycle: Menstrual phase
due to the decrease in estrogen and progesterone secretion signals and demise of the corpus luteum the endometrium degenerates and the tissue breaks down resulting in menstrual bleeding
this moment is defined as day 1 of the menstrual cycle
The endometrial cycle: Proliferative phase
After menstruation the endometrium is restored by the 5th day of the cycle
Proliferation of the basal stromal cells in the zona basalis, and epithelial cells in other parts of the uterus
Stroma give rise to the connective tissue components of the endometrium
All this is stimulated by estrogen from the developing follicles
- estrogen rise early and peak just before ovulation
- induces synthesis of progestin receptors on endometrial tissue as well
The endometrial cycle: Secretory phase
Corresponds with the luteal phase
Vascularization of the endometrium increases, glycogen content increases
endometrial glands become engorged with secretions
Progesterone promotes differentiation of the stromal cells into predecidual cells which prepare to form the decidua of pregnancy and orchestrate menstuation in the absence of pregnancy
-critical for implantation
Polycycstic ovarian syndrome
Most common cause of infertility in females
Frequently manifests during adolescence
Exhibit various combinations of otherwise unexplained hyperandrogenism, anovularion and polycystic ovary
-abnormal ovarian steroidogenesis and folliculogenesis, clinically manifested by androgen excess and anovulation
elevated LH, and low FSH, elevated testosterone
high androgens romote atresia in developing follicles and disrupt feedback relationships
enlarged polycystic ovaries are knowmn to be associated with increased androgen levels (DHEA)
presentation: young, obese, hirsute females of reproductive age, oligomenorrhea or secondary amenorrhea and infertillity
Turner syndrom
Most common cause of congenital hypogonadism
50 percent of cases result from the complete absence of the second X chromosome (45,X genotype)
internal and external genitalia typically are female
Primary hypogonadism
-germ cells do not develop and each gonad consists of a connective tissue filled streak
Because of the ovarian failure, many individuals with turner syndrome have elevated serum concentrations of FSH
Symptoms:
- short stature
- delayed puberty
- non-functioning ovaries
- webbed neck
- swelling/lymphedema of hands/feet
- skeletal abnormalities
- learning disabilities
Menopause
Defined as occuring 12 months after the last menstrual period; marks the end of menstrual cycles
- occurs around 51 years of age
- due to reduction in estrogen and low levels of inhibin therefore no negative feedback of LH and FSH therefore high levels of LH and FSH
can occur naturally, prematurally, (premature ovarian failure), due to surgery or as a result of chemotherapy
symptoms:
- irregular periods
- vaginal dryness
- hot flashes
- night sweats
- sleep problems
- mood changes
- weight gain and slowed metabolism
- thinning of hair
- loss of breast fullness
treatments of menopause:
Most treatment focus on relieving the sign and symptoms and preventing or managing chronic conditions that may occur with aging;
- estrogen therapy
- vaginal estrogen
- low dose antidepressants
- gabapentin (for treatment of hot flashes
