Ovaries and Ovarian Cycle Flashcards
what do the ovaries produce?
oocytes
sex steroids = estradiol and progesterone
protein hormones = relaxin, inhibin, and activin
gamete numbers at
birth, childhood, reproductive years, and menopause
birth = 1 million primordial follicles at prophase I of meiosis
childhood = over half lost through atresia, there are around 400,000 primordial follicles at puberty
reproductive years = ~1,000 lost per cycle through ovulation and atresia
menopause = 1000 primordial follicles
phases of the ovarian cycle
follicular = days 1-14
ovulation = day 14 and 15
luteal = days 15-28
when does luteal regression start?
day 24
when do variations occur in the ovarian cycle
only follicular phase
luteal phase is always constant 14 days
ovarian cycle is under what type of control
hormonal
dominant pituitary hormone during follicular phase
FSH (stimulated by GnRH)
stimulates progression from primordial follicle –> follicle –> ovulation
dominant pituitary hormone during luteal phase
LH (stimulated by GnRH)
stimulates development and degeneration of corpus luteum after ovulation
stages of follicular development
- primordial
- early preantral
- late preantral
- antral
- pre-ovulatory or Graafian follicle
cell types of the follicle
oocyte = egg itself
granulosa = cells that surround the oocyte, epithelial in origin
theca = outermost cell layer, more fibroblast in origin
chromosome number follicular stages
primordial = primary oocyte (46, 4n), meiosis I
primary = primary oocyte (46, 4n), meiosis I
secondary = primary oocyte (46, 4n), meiosis I
- zona pellucida is present
Graafian = secondary oocyte (23, 2n), metaphase of meiosis II
- zona pellucida present
Histology of the ovary
consists of a cortex and medulla
lining the cortex is a single layer of germinal epithelium
–> with many primordial follicles visible deep to it in the cortex
multiple stages of follicular development can be visulaized simulataneous in one image
histology of the primary follicle
multilaminar….if only 1 layer of granulosa cells it could be a primordial follicle
no opening or antrum between the oocyte and granulosa cells
histology of the secondary follicle
with proliferation of granulosa and theca cells (due to FSH)
…we see polarization of the oocyte towards one side and the formation of a cavity (antrum)
the theca divides into
- theca interna (hormone production)
- theca externa (structural)
zona pellucida appears
histology of secondary oocyte
Cumulus oophorus (CO) = granulosa cells surrounding the oocyte
Corona Radiate = first layer of granulosa cells in the CO that touch the ZP maintained at ovulation
there is communication between the oocyte and corona radiata through the ZP (cell processes of CR cells are sent through the ZP)
zona pellucida = protein rich gel secreted by the oocyte
mature Graafian follicle histology
the follicle that is picked for ovulation
similar in appearance to secondary follcile
can extend through the whole thickness of the cortex
the is a endocrine organ!!!!
Follicular atresia
vast majority of follicles undergo atresia via apoptosis
begins at fetal life and continues past menopause
can occur to follicles in any stage
histologically –> will see breakdown and death of granulosa cells and the follicle will degenerate
hormonal regulation during majority of follicular phase
general
GnRH (hypothalamus)
FSH (pituitary)
estradiol (ovary) –> positive feedback on the hypothalamus GnRH release
inhibin B (ovary, specifically granulosa cells)
luteal phase
progesterone reduces levels of what hormones
FSH and LH
due to negative feedback on hypothalamus release of GnRH
LH surge
end of follicular phase right before ovulation
before this (FSH > LH)
leads to high occupancy of LH receptors on the theca cells
why is LH surge more than FSH surge right before ovulation?
granulosa cells produce inhibin B
which inhibits FSH production from gonadotrophs
why do we want to inhibit FSH at the end of follicular phase?
because it largely stimulates follicular development and you don’t need to stimulate another follicle development immediately before ovulation
loss of androgen receptors lead to what? after the LH surge
rapid decrease in estradiol production
what nuclei make GnRH in hypothalamus
arcuate and preoptic
release into primary capillary plexus in the median eminence
pulsatile secretion leads to onset of puberty
ovarian steroid hormones feedback to hypothalamus to regulate pulsatile release
GnRH in late follicular phase
pulse frequency increases
due to positive feedback of estradiol
GnRH in luteal phase
pulse frequency decreases
negative feedback of progesterone
other non-sex steroid hormones that regulate GnRH release
inhibit = dopamine, endorphins, melatonin, CRF
stimulate = NE
structure between FSH and LH
both alpha and beta subunits
beta subunits differ
relative amounts of FSH LH in
childhood
adult, reproductive
menopause
childhood = FSH>LH
reproductive = cycles of LH and FSH
menopause = surge in FSH and LH, FSH > LH again
why surge in LH and FSH post menopause
decreased progesterone in menopause
so loss of negative feedback
measurement of GnRH
too small amounts to measure directly
so measure by measuring levels of LH
male = 8-10 pulses/day with each pulse only a few minutes
female = dependent on time of cycle
–> pulsatile secretion of GnRH is required….continuous GnRH does not maintain LH/FSH
FSH target during follicular phase
granulosa cells of primary follicile (not primordial stimulation since that occurs spontaneously)
LH target during follicular phase
theca interna (early)
granulosa (late)
FSH effect during early follicular phase
stimulates mitosis
induces FSH receptors and gap junctions
induces aromatase to produce estradiol
stimulates inhibin B synthesis in granulosa cells
–> this stimulates androgen production by theca interna and decreases FSH secretion
LH effect during early follicular phase
targets theca interna
stimulates steroid (androgen) production
FSH effect during late follicular phase
with elevated estrogen levels
induces LH receptors on granulosa cells –> low progesterone production
LH effect during late follicular phase
targets granulosa cells to start luteinization and progesterone synthesis
LH surge = high occupancy of LH receptors on theca cells blocks androgen precurosors needed for estradiol synthesis
Steroidogenesis of ovary
second function of ovary besides making oocytes
theca interna = LH stimulates androgen production
granulosa = FSH stimulates inhibib B and androgen synthesis
FSH stimulates aromatase…which converts androgens from theca interna to estradiol
big picture LH and FSH stimulate estradiol
positive feedback of estradiol creates LH surge
major hormones of luteal phase
LH
progesterone
inhibin A
hCG
stages of corpus luteum
corpus luteum of cycle
corpus luteum of menstruation
corpus albicans
corpus luteum of pregnancy
LH effect on corpus luteum in luteal phase
maintains it…
forms from luteinization of granulosa and theca cells
what hormone does the corpus luteum make
progesterone
provides negative feedback
low FSH in luteal phase effect on granulosa cells
make inhibib A which further reduces FSH
corupus luteum of the cycle
takes up the whole ovary
producing androgens
the major endocrine organ now
why does LH drop in luteal phase
negaitve feedback of progesterone
corupus luteum is essentially signaling its own death
nonfunctional corpus albicans
after corpus luteum starts to undergo apoptosis
corupus luteum of pregnancy
hCG from the blastocyst acts like LH
maintaining the corpus luteum throughout the 1st trimester
producing hormones
FSH effect on theca cells during luteal phase
NO effect
LH effect on theca cells during luteal phase
early = increase steroidgenic enzymes and androgens
late = decrease androgens due to high occupancy of LH receptors
inhibin B effect on theca cells during luteal phase
increase androgens
FSH effect on granulosa cells during luteal phase
early = increase proliferation, FSH receptors, gap junctions, aromatase, inhibin B, estradiol
late = increase LH receptors
LH effect on granulosa cells during luteal phase
late = increase luteinization progesterone
inhibin B effect on granulosa cells during luteal phase
NO effect
FSH effect on theca lutein cells during luteal phase
NO effect
inhibin B effect on theca lutein cells during luteal phase
NO effect
LH effect on theca lutein cells during luteal phase
increase LDL uptake
increase androgens
FSH effect on granulosa lutein cells during luteal phaes
increase inhibin A
LH effect on granulosa lutein cells during luteal phase
increase LDL uptake
increase progesterone and estradiol
inhibin B effect on granulosa lutein cells during luteal phase
NO effect
7 steps that can summarize the ovarian cycle
- after GnRH stimulates FSH and LH production –> FSH stimulates aromatase and estrogen production
- FSH increases inhibin B, increasing estrogen production further and providing negative feeback on FSH producing cells
- LH stimulates steroid synthesis from theca interna
- LH increase progesteron production and luteinization in granulosa cells (late)
- low FSH levels stimulate granulosa lutein cells to secrete inhibin A, reducing LH and FSH
- progesterone from corpus luteum provides negaitve feedback, decreasing GnRH
- low LH –> cell death –> corpus albicans
ovarian cysts
fluid filled cavities that originate from unruptures Graafian follicles
Polycystic ovarian syndrome
elevated androgens and LH but reduced FSH
result = bilateral ovarian enlargement with multiple follicular cysts
ovarian tumor
origin can surface epithelium, oocytes, follicular cells, or stromal cells
menopause
faiilure of ovarian follicles to develop
reduced estrogen/progesterone, and inhibin B (loss of negative feedback on hypo and pit)
estrogen deficiency = bone loss, hot flashes, increased coronary artery disease
increase FSH and LH
oviduct
provides proper environment for fertilization
regions = fimbria, infundibulum, ampulla, ishtmus, intramural part
components of oviduct wall
mucosa = simple ciliated columnar with secretory (peg) cells interspersed
peg cells = provide nutrients to secondary oocyte, spermatozza, and preimplantation embryo
lamina propria = highly vascular
muscularis = poorly defined layers, inner circular, and outer long
serosa = highly vascular, loose CT
amulla vs. isthmus of oviduct
isthmus has more muscle and less lumen/folding
fertilization occurs in ampulla
estradiol effect on oviduct
increases cilia and ciliary beat
stimulates secretory activity
increases vascularity of lamina propria
increases vascularity and contractility of muscularis
progesterone effect on oviduct
max ciliary beat, stimulates secretory activity
decreases contractions of muscularis
events at the time of fertiliztion in oviduct
- zona pellucida has receptors for sperm , starts the acrosome reaction
- cortical reaction prevents polyspermaia
- sperm entering nuclues intiates completion of meiosis 2 to form mature ovum and second polar body
- nuclei of ovum and sperm fuse –> zygote
