TOB Female Gen (20)
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- produce female gametes & sex hormone
- are paired organs that can be divided into two portions: outer cortex + inner medulla
- surface = covered by layer of simple cuboidal surface epithelium (considered the source of most common form of ovarian cancer)
- tunica albuginea (a thick CT layer present beneath the epithelium)
- the rest of the cortex contains a compact, richly cellular stroma, which have follicles
- follicles are NOT present in the medulla, which contains CT, interstitial cells, nerves, lymphatics, & large blood vessels
- a structure made of follicular or granulosa cells that surrounds an oöcyte
- it is found in the stromal portion of the ovary CORTEX
- it undergoes a series of steps which cumulates in ovulation
- the oöcyte itself undergoes maturation steps which are completed if there is fertilization
- the earliest stage of follicle development
- each contains a primary oöcyte surrounded by one layer of squamous follicular (granulosa) cells resting inside a thin basal lamina
- the internal primary oöcyte has a large, vesicular nucleus w/ a large nucleolus (it's arrested in the diplotene stage of prophase of meiosis I)
What are the predominant type of follicles present at birth in the ovary as well as before & after puberty?
PRIMORDIAL FOLLICLES arrested in prophase of meiosis I
- primordial follicle histology
- central large oocyte surrounded by a FLATTENED layer of follicular cells
- there is a basal lamina surrounding the whole follicle structure until very late in follicular development
- may also see splotches in the oocyte which can be mitochondria; it has a lot of them
- outside are cells of the CT & the stroma (orient yourself)
(Unilaminar) Primary Follicle
- starting at puberty & at the beginning of every future menstrual cycle chosen follicles (aka those with the most FSH receptors on their surface) begin to mature
- first thing to change is that the flattened follicular cells around the oocyte become cuboidal: this characterizes a primary follicle
- unilaminar primary follicle histology
- follicular cells surrounding the oocyte become cuboidal
- basal lamina is still intact
- these oocytes/follicles becomes larger (esp. in comparison to primordial follicles
Multilaminar Primary Follicle
- produced as a result of granulosa cell proliferation
- cellular stroma immediately around the follicle differentiates into theca folliculi (cells)
- follicle & oocyte are still enclosed by a complete basal lamina separating them from the theca cells
- zona pellucida starts to develop BTWN the oocyte & granulosa cells (contains glycoprotein)
How do nutrients get to the oocyte?
- because there are no blood vessels to the oocyte, nutrients must diffuse through the outer basal lamina through granulosa cells to the oocyte
- even though it's a long distance, nutrient transfer is facilitated by gap junctions between both granulosa cells & the oocyte & granulosa cells (oocyte has long cytoplasmic processes that invaginate & touch granulosa cells through the zona pellucida)
- two layers of cells surrounding the granulosa cells (separated by the basal lamina) made up of theca cells
- theca interna: the has abundant SER + lipid droplets (the appearance of steroid producing/metabolizing cells)
- theca externa: CT-like
- BOTH layers are vascularized
theca interna cells
- express receptors for LH and when signaled they synthesize androgens (androstenedione & testosterone) using cholesterol
- these male hormones diffuse INTO the follicle
- granulosa cells stimulated by FSH make aromatase, which converts the male hormones into estrogens (estradiol & estrone)
Can the granulosa cells produce estrogens directly?
- no, they do not have the capacity to do so
- aromatase, a granulosa cell enzyme converts male hormones secreted by theca interna cells to estrogens for foster oocyte growth
What is the purpose of a high concentration of estrogens in the microenvironment of the follicle?
- it is essential for the development of the oöcyte
- the level of the estrogens can be more than 100X higher in the follicle than in the blood facilitated by sex-hormone binding proteins IN the follicular fluid
Which part of the follicle surrounding the oocyte is vascularized?
- the theca interna is HIGHLY vascularized
- granulosa cells remain avascular throughout the growth of the follicle & are separated from the theca by a thick basal lamina
Secondary (Antral) Follicle
- during this stage, small areas filled with fluid (liquor folliculi) appear between the granulosa cells
- they coalesce to form one large cavity, the antrum
- at this stage in development the oöcyte has reached its full size (0.2mm) & the follicle is about 10 mm in diameter
- the 2ndary stage of follicular development is dependent on estrogens produced locally & the pituitary hormone FSH
- Secondary (Antral) Follicle histology
- antrum: fluid formed between granulosa cells that coalesces
- granulosa cells are at the periphery
- outside of them are the 2 layers of theca cells
- corona radiata: granulosa cells which directly surround the ooctye and separate it from the antrum
- cumulus oophorus: granulosa cells between the corona radiata and the circular follicle that surrounds the whole antrum ('column on which the oocyte sits'); looks like a pedestal
Mature (Graäfian) Follicle
- follicle has reached its largest size (2.5 cm) and can be observed by ultrasound (during IVF)
- immediately before ovulation the antrum increases greatly in size
- oöcyte is found on one side of the follicle, surrounded by a few layers of granulosa cells (corona radiata) on a pedestal of follicle cells (cumulus oöphorus)
During which stage of development do granulosa cells acquire receptors for luteinizing hormone (LH)?
- as a Mature Graäfian Follicle
- this is critical for the development of the corpus luteum later on
primordial -> unilaminar primary -> multilaminar primary -> secondary/antral -> mature/graäfian
- a mid-menstrual cycle LH surge from the anterior pituitary occurs, instigating ovulation
- 16-24 hours after the LH surge, the secondary oocyte, it's surrounding zona pellucida & outer corona radiata detach from the cumulus oöphorus & float in the antrum
- collagenase activity + ischemia from increased antral pressure leads to the formation of a stigma in ovary cortex --> which ruptures, releasing the 2ndary oocyte with an intact corona radiata
- released oocyte is captured by the oviduct (fallopian tube)
How long does the ovum in the oviduct have to get fertilized?
- unless it is fertilized within 24 hours, the ovum degenerates
- if the ovum is fertilized, the zygote undergoes cleavage, and makes the 3-5 day trip to the uterus for implantation
To what age woman does each ovary belong?
- top: old; no follicles/oocytes to be found, only stroma
- bottom: young; filled with follicles
- About 7 million primary oöcytes are present in the fetal ovary by mid-gestation. At birth, about 400,000 oöcytes remain. Only about 450 of these will develop to maturity.
- a process undergone by follicles that don't mature and instead degenerate at various stages and undergo apoptosis.
- it can happen to follicles at any stage of development
- it begins in intrauterine life, becomes prominent at birth & shortly before puberty
- macrophages come in and remove the cellular debris, leaving only stroma cells and collagenous scar
- characterized by cell floating around in antrum, no longer specifically attached where they should be
- a thick structure made of the basal lamina between the granulosa cells and the theca cells during follicular atresia
- some of the thecal cells from atretic follicles may remain and become interstitial cells that (along with the adrenal glands) become sources of sex hormones after menopause
- what remains of the follicle structure in the ovary cortex after the ovum is released
- it becomes a highly vascularized endocrine body who's granulosa cells produces progesterone in order to support a possible fertilization event and a subsequent pregnancy
- Corpus Leuteum Cells
- granulosa cells -> granulosa lutein cells: puffier, pale-staining w/ lipid droplets + abundant SER in their cytoplasm [larger]
- theca interna cells -> theca lutein cells: smaller, darker-staining, still secrete androgens (in response to LH)
- aromatase in the granulosa lutein cells still converts androgens from the theca lutein cells into estrogen & now progesterone
What happens to the Corpus Leuteum if fertilization doesn't take place?
- the corpus luteum of menstruation degenerates after about 14 days
- lipid droplets get bigger, sign of dying Corpus Leuteum/cells
- 'white body'
- all corpus luteum eventually will degenerate and is replaced by dense CT scar called corpus albicans
- the scar is larger for a corpus luteum of pregnancy than that of a corpus luteum of menstruation
What happens to the Corpus Leuteum if fertilization does take place?
- the corpus luteum of pregnancy enlarges & is maintained for 6 months by human chorionic gonadotropin from the placenta
- after that it gradually declines but persists until the end of pregnancy
- in addition to estrogen and progesterone, it secretes relaxin, a polypeptide hormone which softens and dilated the cervix, inhibits uterine contraction, & loosens the fibrocartilage of the pubic symphysis, allowing the pelvic outlet to enlarge during parturition (birth)
How can you tell the difference between a corpus leuteum and a corpus albicans?
- Leuteum: highly cellular (lutein cells)
- Albicans: just a scar, no cells, mostly collagen fibers
a glycopeptide hormone secreted by the granulosa cells that reduces FSH secretion in the pituitary
a glycopeptide hormone also secreted by the granulosa cells that stimulates the release of FSH from the pituitary
oogonia that have already undergone mitosis then begin meiosis to become primary oocytes, which are arrested in _______________ from before birth until puberty.
- primary oocytes are arrested in prophase of meosis I from before birth until puberty
- - they don't proceed to meiosis II until ovulation
What's one difference between male and female meiotic division?
- In females there are unequal meiotic divisions that produce a primary oocyte and a small polar body --> then another unequal meiotoc division that produces a secondary oocytes and a second small polar body
- In males, meiotic divisions are all equal and all meiotic derivatives produce spermatids
When is the primary oocyte in a primordial follicle?
After the zona pellucida and the single layer of follicle cells form
When is the primary follicle formed?
when the primary oocyte enlarges during puberty; follicular epithelial cells become cuboidal and then columnar, forming the primary follicle
What happens after a primary oocyte finishes Meiosis I?
- It releases the first polar body and then enters Meiosis II where it is arrested at METAPHASE (II)
- arrested at metaphase II it's called a mature, secondary oocyte
What triggers a secondary follicle to rupture, expelling the secondary oocyte by contraction of the smooth muscle-like _____ cells?
- prostaglandins - lipid paracrine hormone
- the smooth muscle-like THECA cells contract and expel the secondary follicle
What surrounds the ovulated secondary oocyte?
the zona pellucida & one or more layers of follicle cells called the corona radiata
How soon after the LH surge does ovulation occur?
within 12-24 hours
What happens to the corpus luteum IF an oocyte is fertilized?!
- it becomes the corpus luteum of pregnancy, fortified by increased progesterone production
- this corpus luteum of pregnancy is functional for 20 weeks
- after this 20 weeks the placenta makes enough estrogen & progesterone to support the pregnancy
What prevents the corpus luteum from degenerating and where is the source of this prevention?
- human chorionic gonadotropin (hCG) prevents the corpus luteum from degrading
- hCG comes from the implanted blastocyst (embryo)
Oviducts (Fallopian Tube)
transport the egg; is the site for fertilization, transport the zygote
- with endometrium & myometrium; site of fetal development
- menstrual cycle involves proliferative, secretive, ischemic and menstrual phases
- Uterine cervix contains mucous glands
Menstrual Cycle Phases (4)
- 1) Menstrual Phase: days 1-5
- 2) Proliferative Phase: days 5-14
- estrogen levels rise, stimulate re-growth of endometrium functional layer
- 3) Secretory Phase: days 14-27
- estrogen levels peak then fall
- progesterone levels are high
- if no fertilization occurs, corpus luteum degenerates, estrogen & progesterone levels fall, and the secretory endometrium enters the ischemic phase
- 4) Ischemic Phase: days 27-28
- progesterone & estrogen levels fall rapidly and the functional endometrium becomes ischemic
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