What part of the ovary do neurovascular elements run?
Medulla
What is the cortex of the ovary composed of?
Dense cellular stroma
What resides inside the cellular stroma?
Ovarian follicle
Primary oocytes are arrested in what phase of meiosis?
Diplotene stage of prophase I
How do follicle cells stimulate oocyte growth?
What does it bind?
Release of c-kit ligand (stem cell factor)
c-KIT receptor
The appearance of what signals a primary follicle?
Cuboidal granulosa cells
Pre-antral follicles fail to complete meiosis and the oocyte begins to grow. What does it secrete?
What is the fx of the secretion?
ZP1, 2, 3
Species-specific binding site for sperm during fertilization
How do Granulosa cells and oocyte maintain contacts?
Gap junctions
Thecal cells are analogous to what?
Major product?
Leydig cells
Androstenedione
Early natural follicles are depended upon what for normal growth?
FSH
What do mural Granulosa cells form?
Where are they located?
What happens to them?
Outer wall of follicle
Close to thecal layers
Become highly steroidogenic and remain in ovary after ovulation to differentiate into the CL
The innermost layer relative to the oocyte of cumulus cells maintains contact how?
Gap junctions and adherens junction
Larger antral follicles have meiotic competence but are still arrested until when?
Via what mechanism?
Mid cycle LH surge
elevated cAMP levels in mature oocyte
What converts androgens to estradiol-17B?
Mural Granulosa cells
What stimulates proliferation of Granulosa cells?
What else does it induce?
FSH
Expression of CYP19-aromatase
Mural Granulosa cells of large antral follicles producing increasing amounts of what?
When?
Inhibin B
Early follicular phase
When does the process of follicle selection occur?
Early follicular phase
What converts androstenedione to estrone?
Aromatase (CYP19)
Aromatase converts testosterone to what?
Estradiol-17B
What receptors do thecal cells express?
What do they produce?
LH
Androgens
What receptors do Granulosa cells express?
What is present in granulosa cells And what does it do?
FSH AND LH receptors
Aromatase which converts androgens to estrogens
What is the periovulatory period?
Lasts how long?
Onset of LH surge to ovulation
32-36 hours
The CL is made how and of what?
Biogenesis from remaining thecal and mural Granulosa cells
Main product of CL?
Secondary product?
Progesterone
Estrogen
Before ovulation, the follicle presses against the wall of the ovary forming what?
Bulge called the stigma
LH surge induces release of what?
Inflammatory cytokines and hydrolytic enzymes from Theca and Granulosa cells
As an indirect response to LH surge what does the oocyte release?
What does this do?
What do these products do?
GDF9
Hyaluronic acid and other extracellular matrix components
Expansion of the oocyte complex, making it easier for sperm to locate
What are some angiotensin factors the Granulosa cells produce to increase blood supply to the new CL?
VEGF, angiopoietin-2, bFGF
What converts androstenedione to testosterone?
17B-HSD
Major thing that does this
What happens during lute ionization of the Granulosa cells?
Inhibits Aromatase and estrogen formation
Causes vascularization of Granulosa cells increasing LDL receptor expression
CL lives how long?
Saved by what?
14 days
hCG from implanted embryo
When does progesterone production increase?
When does it peak?
After onset of LH surge
Peaks midluteal phase
What does estrogen do after LH surge?
Decreases but then peaks at midluteal phase
What happens to FSH and LH levels during the Luteal phase?
Why?
DEC
Negative feedback from progesterone and estrogen
What do Granulosa lutein cells secrete?
What does this do?
Inhibin A
Suppress FSH
What is thelarche?
Breast development
What does the follicular phase coincide with?
Luteal phase?
Proliferative
Secretory
These are endometrial phases
Granulosa cells increase production of what to stimulate endometrial growth and maturation?
Estrogen estradiol
What 2nd messenger does GnRH work through?
Gq -> PLC -> PKC, DAG, IP3
How is GnRH released?
High levels of what, typical of the late follicular phase sensitize gonadotrophs to GnRH?
Rhythmic pulses
Estradiol
What do activins stimulate?
Made from where?
FSH release
Granulosa cells
What are inhibins composed of?
Activins?
Alpha beta heterodimers
Beta A and B Heterodimers
When do estrogens exert negative feedback control?
Progestins?
High and low [ ]’s
ONLY high [ ]’s
Where are estrogens derived from in the female?
Ovary
Adrenal gland
Peripheral conversion in adipose
How does estrogen affect basal body temperature?
When?
Lowers it
Pre-ovulation
How do high levels of progesterone affect basal body temperature?
When?
Raise it
After ovulation
When is the endometrium restored after menstruation?
What proliferates?
Day 5
Basal stromal cells
Epithelial cells from uterus
How does progesterone act in accordance with estrogen?
What does it inhibit/stimulate?
Opposes its action on endometrium and functions as anti estrogen
Inhibits epithelial cells proliferation but promotes proliferation of endometrial stroma
Stimulates 17B-HSD and sulfotransferase
What promotes the differentiation from of stromal cells into predicdual cells?
Progesterone
What do oral contraceptive pills suppress?
FSH and LH
How do progestin-only OCP work?
Cause the cervical mucus to thicken and become sticky and insufficient
What are oligomenorrhea and amenorrhea due to?
Dysfunction or cessation of the HPA ovarian axis
What is menorrhagia?
Loss of greater than 80mL of blood
What is endometriosis?
What tissue is most commonly involved?
Clinical presentation?
Tissue that normally grows inside the uterus grows outside it
Ovaries, bowel or tissue lining the pelvis
Pelvic pain, dysmenorrhea, dyspareunia, constipation, infertility
What is most common infertility in women?
Caused by what?
PCOS
Hyperandrogenism, anovulation, polycystic ovary
Enlarged polycystic ovaries are associated with what?
Presentation?
DHEA
Young, obese, infertility, oligomenorrhea, insure females
Describe the following levels in PCOS:
LH
FSH
Testosterone
Elevated
Low
Elevated
Turner syndrome due to what?
What are the external and internal genitalia like?
Clinical presentation?
Congenital hypogonadism
Female
Webbed neck, short, low-set ears, shout 4th metacarpals, sexual infantilism
Menopausal women have what kind of levels of FSH and LH?
Why?
High
Low levels of estrogen and Inhibin -> no (-) feedback
What are some signs of peri menopause?
Irregular periods Hot flashes Vaginal dryness Night sweats Mood problems Etc
What is considered part of the female reproductive system?
Ovaries, breasts, reproductive tract