Female reproductive physiology
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So in general broad terms explain to me the life of a follicle?
Well so we all start with primordial follicles that become 1ry follicles that then become 2 follicles. Once those 2ry follicles have an antrum then they become early antral follicles. Most of them die but one lucky follicle gets selected to become a pre-ovulatory or graffian follicle. That follicle will ovulate, the egg will be released into the oviduct, some of the cells stay behind and those that stay behind become the corpus luteum and the corpus luteum hangs around for 2 wks and then regreses to become the corpus albicans.
Explain oogenesis in as much detail as you can from the start..
- So, we start off during fetal life with oogonia that undergo lots of mitosis and we have several million oogonia in the ovary at the time of birth and they will go mitosis and differentiation and then they become 1ry oocytes. Those 1ry oocytes will undergo mitosis and become arrested in prophase of meiosis 1. So the net result is that by the time a little baby girl is born, it will have all the 1ry oocytes its ever going to have.. They 1ry oocyte stays arrested in miosis 1 until it is triggered by the LH surge that happens in the middle of the the menstrual cycle. The oocyte that sees the LH surge (the one that is in the pre-ovulatory follicle is the only one that responds to LH) then begins miosis 2 and miosis 2 is completed with fertilization.
- Tidbit of information, after miosis 1 is completed we get an unequal division of the cytoplasm but the chromosomal content is the same so we get a single secondary oocyte but we also get a little polar body that hangs on the outside and after 2 miosis we also get a 2ry polar body.
So explain why there is such a high rate of genetic abnormalities in women who have children at an older age.
So, primary oocytes are arrested in prophase of miosis 1 and this is a very dangerous time for eggs.
When is there ovulation?
Ovulation occurs at the end of of miosis 1..
In what stage does the the oocyte need to be in for it to be fertilized and make a cute whittle baby?
An oocyte has to be a secondary oocyte and then it waits to see if it gets a sperm to fertilize it..
What does the LH surge do?
- it triggers the completion of miosis 1.
- it makes ovulation happen
- it causes a CL
So what are polar bodies?
So we get polar bodies after miosis 1 and 2. and it happens due to an unequal division of cytoplasm.
Explain how the chromosomes per cell and the chromatids per chromosome vary in an oocyte?
- oogonia: 46 chromosomes per cell 2 chromatids per chromosome
- primary oocyte: 46 chromosomes per cell and 2 chromatids per chromosome
- secondary oocyte: 23 chromosomes per cell and 2 chromatids per chromosome
- mature egg (ovum): 23 chromosomes per cell and 1 chromatid per chromosome
What types of follicles have 1ry oocytes?
- early antral
When do follicles start growing?
Girl, all the time! they grow even before birth
is there synchronicity in the oocyte maturation and folic growth?
Nope... They each to their own thang ya know how it be..
So lets get a little more in depth.. What are the changes that we see as the follicle develops?
- Primordial follicle: single layer of flattened granulosa cells (follicular cells)
- Primary follicle: granulosa cells become cuboidal and there is also a basal lamina now
- secondary follicle: Now we start getting multiple layers of granulosa cells (early theca follicle, follicular cells and then the early theca follicula)
- early antral follicle: antrum starts to form. We now have the theca folliculi, granulosa cells, zona pellucid and basement membrane
- Grafian follicle: so now we have theca interna, externa, membrana granulosa, corona radiata, antrum (like huge), zona pellucid and the cumulus and the mural granulosa cells
So you being the amazing student that you are realize that there is something that does not look like a 1ry oocyte in the antral follicle.... How the heck can that be?
Well, the only antral follicle that wouldn't contain a 1ry oocyte is the single preovulatory follicle and the only time that that would ever happen is in that brief period of time after it has seen the LH surge.
So explain gonadotropin independent and dependent. Like what is it and what does it do?
So gonadotropins are important int he follicle growth but only in like the last 15 days. Before that (i.e. the first couple of months), the follicle is going to develop that is why even before the girl has gone through puberty when the gonadotropin is low you can still see follicles in different stages but once the follicle develops an antrum it becomes gonadotropin dependent (i.e. dependent of FSH)
What is responsible for secreting substances to make the antrum?
The granulosa cells start secreting substances to cause fluid in the antrum and make it bigger.
So explain in detail the ever so fun menstrual cycle.. You go through it every month what do you mean you dont remember??! yes you do!!!!!!! :)
On the first day of menstruation the LH and the FSh levels increase which causes multiple early antral follicles to grow and make estrogen which causes the circulating estrogen levels to increase. Of the group of antral cells that were growing, 1 of them becomes dominant and that one is like super amazing at making estrogen so the estrogen plasma levels increase even more and those same follicles that were making estrogen also make inhibit which feedbacks to the hypothalamus and the pituitary to decrease FSH. Before there is ovulation and the LH surge, estrogen feedback changes from negative to positive. It acts on a different set of neurons to dump all gnRH so we get the LH surge. That LH surge causes the oocyte to complete miosis, ovulation to occur, and the corpus luteum to form which makes progesterone and some estrogen. So progesterone increases and so does inhibin and now these 2 hormones go back and do -feedback and FSH and LH are inhibited. After 2 weeks, the corpus luteum begins to regress. Progesterone and estrogen fall and then that - feedback is suppressed so the FSH and the LH are back to where we started
What is the fate of most of the follicles?
Well follicles grow since birth of the child and some of them do grow but most of them die through the process of atresia. We start off with millions of follicles but by the time we get to puberty we only have 100,000 follicles left.. *sigh*
So how does the body decide which follicles actually go on to grow?
Ok so this is a tricky question because the follicles will grow regardless, follicles grow like everyday but once a follicle gets an antrum that is when it becomes dependent on FSH. So if the FSH is high enough that follicle or follicles will continue to grow now dependent on that FSH. From those 2-8 follicles that get recruited, one is picked to become that mature egg to ovulate
How is the dominant follicle selected?
So that follicle has 3 main things: enhanced vascularity, increased FSH receptors and enhanced cAMP responsiveness which increases its ability to use FSH bc the follicles at this point are making so much estrogen nd inhibin that they are starting to drive FSH down so the other follicles are basically getting starved of that FSH
What hormones have an effect on the cervical mucus production and why does it make sense?
- So estrogen causes the cervical mucus to be thin and watery and this makes sense bc this is around the time of ovulation so we want the sperm to get to the egg
- Progesterone causes the cervical mucus to be thick and sticky and this makes sense since there is a probable fetus there so we need to make sure that the environment is safe
So a woman comes to your clinic and wants to know if her cervix mucus was appropriate for pregnancy.. (yea women are weird..) so what do you want to see under a microscope, what dont you want to see?
So there should be ferrying in there in order to allow the sperm to go through to the egg, if there is no ferning then the sperm won't be able to get through as easy
OK so what is the endocrine regulation of female reproduction.
Basically, memorize this.. Know this cold.. Sigh
How is GnRH released?
- In a pulsatile fashion but the pulses very by what phase of the menstrual cycle you are in.. Ie
- early follicular phase: 1 pulse/hr
- late follicular phase: 2 pulses/hr
- luteal phase: 1 pulse/4 hrs
So explain to me how the ovarian follicle makes estrogen?
So the ovarian follicle has theca and granulosa cells. LH acts on the theca cells and they make androgens, they cross the basement membrane and they are converted into estrogens by the granulosa cells under the influence of FSH
Soo what makes estrogen in the ovarian follicle and why?
So the granulosa cells are the ones that make the estrogens from the androgens thanks to aromatase.
So we need theca cells to make androgens and then we have to transport these into the granulosa cells to make the estrogens? Why can't the granulosa cells just self sufficient and do it by them damn selves?!
Well, the granulosa cells dont have the enzymes necessary to convert progesterone into the androgens. It doesn't have 17 hydroxylase and it also des not have 17,20 lysase or CYP17 for both idk
What are the different estrogens and when can we expect to find them?
- Estrone- menopausal- 1 hydroxy
- estradiol- reproductive years- 2
- estriol- preg- 3
What are the effects of estrogen?
- Brain: maintains temp and it inhibits gonadotrophin secretion, and may delay memory loss
- Heart and liver: increases HDL, decreases LDL and increases SHBG
- Breast: breast growth in puberty, growth and branching of the ducts during pregnancy, and it inhibits lactation during pregnancy
- Ovary- no direct effect
- Vagina: stimulates maturation of vagina and helps maintain a lubricated and thick vagina
- bone: maintains bone density
So what are the different progestins and what makes it
- Progesterone: made by the CL and placenta during pregnancy
- 17 Alpha hydroxy progesterone: it is only produced by the CL
What is major side effect of the synthetic progestins?
they can have androgen activity
What are the progesterone effects on the body?
- Regulates the gonadotropin secretion
- makes cervical mucus production thick and sticky
- In the endometrium it converts it from a proliferating to a secretory endometrium
- in the myometrium it inhibits contractions of the endometrium which is particularly important in the pregnant woman
- it stimulates growth and branching of the ducts
- inhibtis lactation
- It also increases basal temperature that is why you can tell when the patient has ovulated
What are they symptoms of menopause?
- thinning of vaginal epithelium
- loss of secretions
- decreased breast mass
- bone loss
- hot flashes
- increased coronary disease
- emotional instability
Why does a woman go through menopause?
So there is a loss of estrogen due to the loss of the follicles in the ovary.
Why can two patients have variable menopause symptoms?
So one of the main things is weight. A patient who is obese will probably have a better time since there is LH that stimulates the ovarian stroma to produce androsteneodine and this gets converted to estrone by the aromatase which is in the adipose tissue so a thin patient has less of this fat and therefore can't make as much estrone.
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