Female Anatomy
Female Reproductive Tract Anatomy
Functions of the female reproductive tract
reproductive organs controlled hormonally
endocrine function: ovary, uterus, fetus, placenta, pituitary gland, hypothalamus, pineal gland
exocrine function: female gamete production
houses the oocyte (egg)
the female gamete
transports sperm and oocyte/embryo via stimulation of:
myometrial contractions
oviductal contractions
facilitate the events of fertilization
assists with the passage of sperm from the site of deposition to the oviduct
provide environment for embryo and fetus
oviduct
very early in pregnancy
uterus
the remainder of pregnancy
give birth to fetus
dilation (effacement) of the cervix
strong uterine contractions
“recovery” to become pregnant again
uterine involution
return to a state of positive energy balance
provide nutrients to young
lactation
stimulate mammary gland development
Tubular Layers of the Tract
Layers of tract tubes (superficial to deep)
serosa
simple squamous connective tissue
cover the surface
muscularis
double layer of smooth muscle
outer longitudinal layer
inner circular layer
gives the ability to contract
contractions are necessary for:
transport of secretory products, gametes, early embryos, expulsion of fetus and fetal membranes during parturition
submucosa
varying thickness
houses blood vessels, nerves, and lymphatics
supporting tissue for mucosa
mucosa
varying type of mucosal epithelium
dependent on location
lines the lumen
Supporting Structures
Broad Ligament
supports and suspends the ovaries, oviduct, uterus, cervix and anterior vagina
developed by partial fusion of peritoneum to form a double layered connective tissue sheet
houses vascular supply, lymphatic drainage, and nerves
components
mesovarium
anterior/cranial portion
attaches to and supports the ovary
houses the blood and lymphatic vessels and nerves that supply the ovary
forms the hillus of the ovary
in the bitch:
Ovarian Bursa
an extension of the mesovarium that almost surrounds the ovary in dogs
fat-covered peritoneal lining
mesosalpinx
thin, serous part
surrounds and supports the oviduct (salpinx)
serves as a bursa-like pouch that surrounds the ovary
helps to orient the infundibulum so that ova released at ovulation have a high probability of being directed to the oviduct
mesometrium
largest and most visible part
supports the uterine horns (cornua) and uterine body
dorsal portion is continuous with the dorsal peritoneum
thus the uterus “hangs” from the dorsal body wall
Utero-Ovarian Ligament
attaches ovary to uterus
other name:
proper ligament of the ovary
Blood Supply
General
presence of a functional CL will increase blood flow
example: ewe
blood flow increases from 1mL/minute to 3-7mL/min as CL develops
ovarian pedicle
ligament containing blood vessels that nourish the ovary
Ovarian Artery (Utero-Ovarian Artery)
supplies: ovaries, oviducts, potion of uterine horn
return route: utero-ovarian vein)
Middle Uterine Artery
supplies: remainder of uterine horns and uterine body
in the cow:
~5 months gestation
enlarges during middle and late pregnancy
can be palpated as an aid in pregnancy detection
a palpable vibration - fremitus “swoosh”
cannot feel fremitus in mares, doesn’t seem to develop
Hypogastric Artery
supplies: cervix, vagina, vulva
External Organs/Structures
Perineum
region surrounding the anus and vulva and covers the pelvic outlet
dorsal to caudal
Anus → cutaneous bridge → dorsal commissure → labia → ventral commissure
Vulva
consists of two labia (major and minor) and meet in the medial portion of tract to form the dorsal and ventral commissures
the labia form a closure to keep foreign material out of vagina
labia majora (external)
labia minora (internal)
labia constituents
skin (integument)
sebaceous and sweat glands, and hair follicles
mainly adipose tissue
imbedded in small bundles of smooth muscles known as constrictor vulvae
these insure the labia stay side by side
clitoris
female homologue of the penis
erectile tissue covered with stratified squamous epithelium
erection caused by onset of estrus with high estrogen levels
highly innervated (sensory)
not known to have a functional significance in domestic animals
cow: buried in mucosa
mare: well developed
sow: long, sinus
functions:
external opening to the female reproductive tract
first effective barrier to combat external environmental infections
protects the internal reproductive organs from ascending infections
passage of urine
opening for mating
portion of birth canal
in a freemartin vulva is not open, but rather fused
Caslick’s procedure
surgical closing of the upper part of the vulva of a mare
performed on mare’s with abnormal or disfigured vulvar anatomy
required reading:
Caudal Portion of the Internal Tract
Vestibule
otherwise known as the caudal/posterior vagina, its serves as the “opening” to tract
functions:
common area for both urinary and reproductive tract
stimulates male for copulation
passage for fetus during parturition
develops from the ventral part of the cloaca
no secretory glands, but epithelial does produce some secretions
both a part of the urinary and genital systems
extends from the external urethral orifice to the labia
contains:
gartner’s tubules (ducts)
open directly into the vestibule and are blind sacs
no apparent function
known as an embryonic remnant of the male reproductive system of the embryo (Wolffian duct)
Wolffian duct becomes vas deferens in the male and degenerates in female
major vestibular glands
also known as Bartholin’s glands
located in the caudal portion of vestibule in the submucosa
actively secrete mucus-like material and pheromones during estrus
pheromones: airborne chemical messages
cow:
left and right glands
single excretory duct
mare and sow:
multiple minor glands
large number of small excretory ducts
suburethral diverticulum
not present in mare & bitch
present in domestic ruminants, pigs and camelids
small, blind pouch in the floor of vestibule that lies immediately ventral to the urethral opening
blind pocket ventral to orifice
sits below shelf that separates it between the urethra
function unknown
cautions when AI’ing, don’t want to stick rod in pouch
can be used as a landmark for the insertion of a urinary catheter
urethral tubercle
bitch ONLY
bulb or ridge-like structure protruding caudally from vagina into the vestibule directly above urethral opening
varies in size
covers and contains urethral opening
transverse vestibulovaginal fold
mare ONLY (“open” tract)
also known as the transurethral fold or intravaginal transverse fold
overlies the external urethral orifice and separates the vagina from the vestibule
fold of tissue in the vagina that blocks and prevents the backflow of urine into the RT
serves as a secondary barrier for the uterus against external contaminants
seals vagina
resistance against speculum indicates good tone and function
vulvo-vaginal sphincter muscle
between vagina and vestibule, behind urethra
contracts (closes off) when urinating so urine does not breach reproductive tract
cow, ewe, goat, pig (mare)
mare has transurethral fold to help direct urine outward
hymen
membrane at the junction of vagina and vestibule
Vagina
functions:
copulatory organ, site of semen deposition in some species (fornix vagina), site for expulsion of urine during micturition, passive birth canal
poorly organized and ill-defined muscular layer
well developed and highly adaptive mucosal epithelium
no glands
secretions come from passage of plasma components as well as from cervix
pH is acidic (5.7)
bacteriostatic
stimulates glans penis in some species
temperature and pressure
artificial vagina (AV)- correct water temperature and water pressure
caudal vagina (vestibule)
originates from an invagination of the urogenital sinus
stratified squamous epithelium
secretory and thickness of epithelium changes with endocrine status
estrogen dominance (estrus) - thickens dramatically
mechanically protects vagina during copulation
thickened mucosa prevent microorganisms from entering the vasculature in the submucosa
cranial vagina
originates from paramesonephric ducts and fuses with caudal vagina
high degree of secretory activity from columnar epithelium and ciliated columnar epithelium, (luminal epithelium)
fornix vagina
NOT in the sow
protrusion of the cervix into the cranial vagina
forms a crypt, or pocket
spermatozoa are deposited in the fornix vagina by the bull during live-cover
composed of columnar epithelial cells
as an extension of the cervix, it secretes high amounts of mucus during estrus
Cervix
relatively thick-walled, non-compliant
made of muscle and connective tissue
surface covered with columnar and some ciliated columnar epithelium
layers:
serosa, outer muscular layer, deep stromal layer, epithelial and superficial stromal layer, cervical lumen with corresponding structure
functions:
barrier to and transports sperm
mucus and anatomy of cervix act as a sperm filter
prevents large numbers of sperm from reaching oviduct
first sperm barrier in cow, ewe, doe, bitch and queen
not involved as a barrier in the sow or mare
produces long strands of mucus
mucus production for lubrication, prevention of MO’s from entering uterus and transport of sperm
reservoir for sperm until capacitation
sperm enter the crypts and folds of cervix
crypts and folds are covered with columnar epithelium, some ciliated
protects sperm for a long period of time
provides a favorable environment for sperm as they move into the uterus
conditions in cervical mucus favor sperm motility
majority of sperm (~90%) is lost out of the vagina
retrograde transport
blocks bacterial invasion during pregnancy
mucus is highly cross-linked
cervix constricts tightly
leukocytes are present to kill bacteria (MO’s)
cervical seal of pregnancy
cervical mucosa produces a mucus secretion which forms a mucus plug that helps close the cervical canal
birth canal
cervical plug liquifies
cervix dilates to permit fetal expulsion at parturition
very dynamic structure
remodels itself at the end of gestation to allow parturition
stimulates the development of maternal behavior
isolates uterus from external environment during pregnancy
by forming a barrier made of highly viscous mucus
mucus flows from cervix towards exterior
lubricates vagina during copulation
mucus flushes out foreign material from copulation
including sperm
minimizes microorganism contamination in uterus
biochemical and physical properties change depending on stages of estrous cycle
transportation vesicle of spermatozoa
responsible for isolation of the conceptus within uterus from external environment
progesterone causes mucus to become viscous
forms the cervical seal of pregnancy
viscous mucus “glues” folds of cervix together
thus, foreign material cannot enter uterus during pregnancy
disruption of this seal will typically cause abortion
because microorganisms are able to access the interior uterus
causing infection and subsequent embryonic death
Cervical Mucus
under estrogen control = thin and watery
conditions in cervical mucus favor sperm motility
sperm enter parallel strands of mucus in the vagina and are transported to the cervical crypts and folds
muscular action of vagina and cervix may aid in sperm movement
two types:
sialomucin
low viscosity, long strands
“privileged pathway”
direct pathway for sperm
most don’t make it here
sulfomucin
high viscosity, ferning pattern
forms a trap/selective
during estrus:
clear, watery long parallel strands (estrogen)
during diestrus:
little mucus, jelly-like mucus cross-linked by disulfide bonds (progesterone)
cervical ripening
complex process of modification of cervical tissue that enables dilation of the cervix at parturition
cervical smooth muscle tissue
may play a role
collagen fibrils are denatured and digested as part of an inflammatory cascade
characterized by:
further decrease in collagen concentration
increase in collagen denaturation and water imbibition
results in cervical tissue with an extremely soft, watery and well-distensible (swelling) character
cervical tissue is able to dilate
give way to pressure exerted by the fetal membranes or the fetus when the uterus contracts
dynamic characteristics
cervix is very hard and rigid during estrus
composed of thick connective tissue
crypts and folds increase surface area for sperm reservoir
cervix tightly closed except during estrus (standing heat)
anatomy varies between species
cervical canal (lumen) fold(s) or ring(s) protruding into the cervical canal
single- bitch, queen
no elaborate folds or rings
relatively smooth
portion of cervix protrudes into cranial vagina
bitch ONLY
quite small, thick-walled compared to uterus and vagina
queen ONLY
multiple- cow, ewe, sow, mare
several rings form interlocking finger-like projections
cow and ewe ONLY
called cervical rings/annular rings
protrude into the lumen
primary function of cervix is to produce mucus during estrus
cow has 3, 4-5 rings
in beef cows ~17% of all cases of dystocia are of cervical origin
ewe cervical os classifications:
duckbill, slit, rose, papilla, flap
Interdigitating pads
sow ONLY
also called interdigitating prominences
smaller quantity of mucus produced
interdigitations require special penile adaptations in boar
boar has corkscrew or spiral twist in glans penis so it becomes “locked” in cervix
thus, semen deposition occurs in cervix of sows
large volume of semen → quickly enters uterus
longitudinal folds
conspicuous, loose folds of mucosa protruding into the vagina
mare ONLY
no rings
but many longitudinal cervical folds
continuous with endometrial folds of uterus
smaller quantity of mucus produced
mare’s cervix is soft and pliable during estrus and flattens on floor of pelvis
during pregnancy is tight and closed
there are no obstacles in the mare after the fornix vagina
cervical folds
doe only
cervical os classifications:
star, duckbill, crescent, spiral, cluster, bump
semen deposition of stallion and boar
ejaculate through the cervix
stallion:
glans penis bells out and expands cervix
force of ejaculation sends semen directly into the uterine body
boar:
corkscrew penis
glans penis locks into interdigitating pads of the cervix
volume of semen (300-400mL) moves into the uterus
UTJ is more functional in sow to control sperm numbers entering the oviduct
Cranial Portion of Internal Tract
Uterus
organ of pregnancy
connects cervix to oviducts
consists of two uterine horns (cornua)
primary functions:
sperm transport and motility
transports sperm when female is in estrus
estrogen stimulates myometrial contractions so that sperm move to site of fertilization
viable sperm (motility) are important so that they are not absorbed
absorption and phagocytosis
occurs by uterine epithelium and leukocytes (immune cells) which fight infection
luteolysis and control of cyclicity
involved with regression of the CL
if not pregnant
uterine endometrium releases PGF2a to cause CL to regress
if pregnant
embryo provides chemical signal which allows CL to be maintained
"maternal recognition of pregnancy”
environment for preattachment and sustainment of embryo
uterine secretions stimulated by estrogen and progesterone
proper timing of embryo and uterus is important for embryo transfer
maternal contribution to the placenta and development of fetus
quiescent myometrium (due to progesterone)
immunological protection from rejection by maternal immune system
muscle contractions
expulsion of the fetus and fetal placenta
strong rhythmic myometrial contractions (progesterone is low)
move towards oviduct during estrus (standing heat)
following ovulation:
towards cervix until progesterone increases from CL
recovery from pregnancy
uterine involution
myometrial contractions and enzymatic activity shrink uterus back to normal size
components of the uterus:
uterine horns
two cornua (horns)
length:
Pig- 4-5ft.
Cow- 7-8in.
uterine body
fusion between horns (common opening to both)
allows transuterine migration
in ewe, mare, pig, dog, cat
site of semen deposition sow and mare
also during artificial insemination…
tissue composition of the uterus
serosal layer
perimetrium
part of the peritoneum
continuous with serosal layer covering the mesosalpinx
quite thin, almost transparent
above muscle layer
outer serous layer continuous with peritoneum
blocks adhesions
muscularis layer
myometrium
beneath serosal layer
two layers
outer longitudinal layer of smooth muscle
has creases or small ridges that run cranial → caudal
inner circular layer of smooth muscle
beneath longitudinal layer
cells wrap around uterine horn in circular fashion
several physiologic responsibilities
provide motility for the uterus
form of contraction
peristalic contractions “worm-like”
uterine tone
has high degree of tone (partial state of contraction)
NOT in the mare
influenced by high estrogen
can be palpated
estrogen dominance → turgidity/hardness
progesterone dominance → soft/flaccid
EXCEPT in early stage of mare pregnancy
appropriate because during this time, embryo will enter uterus for attachment
if it was highly motile or hard in tone, it would minimize successful attachment of conceptus
related to transport mechanisms for sperm and mucus-like material produced by uterus
parturition
during parturition, muscle is a major driving force for expulsion of fetus and fetal membranes
mucosa + submucosa layer
endometrium
cells of this inner uterine layer produce prostaglandin F
2acauses luteolysis
corpus luteum regression if animal is not pregnant
provides point of placental attachment and glands provide secretions for embryo development
layer 1- submucosal layer
predominantly connective and supporting tissue
origin of uterine glands
functionality changes during estrous cycle
“waxing and wanting”
secretory activity of glands changes as a function of the current stage of the estrous cycle
layer 2- mucosal epithelium
responsible for secreting materials into lumen of uterus
enhance embryo development and sperm viability
uterine glands
develop from mucosal epithelium
produce materials important to the survival and function of the preimplantation embryo
penetrate into submucosa and begin to coil under influence of estrogen
reach full secretory capacity under progesterone dominance
bitch ONLY
uterine glands serve as a temporary storage site of sperm following insemination
not known if these sperm are later released to accomplished fertilization
endometrial species differences
human
endometrium of uterus is sloughed to the exterior
domestic mammals
endometrial glands are not sloughed
species differences of placenta formation
ruminants
caruncles
small protrusions from surface of endometrium
highly vascularized, nonglandular
develop maternal side of placenta if embryo attaches
sow and mare
many endometrial folds
folds provide uterine surface for development of placenta
queen
placental “scars”
caused by marginal hematomas (hematophagous zones)
bands of maternal hemorrhage at the margins of the zonary placenta
product of hemoglobin breakdown
from hemosiderin macrophages
iron-storage complex
pigmented regions of the endometrium
represent sites of previous placental attachment
appear as bands around luminal surface
indicative of zonary placentation
not truly scars
rather, zones of uterine repair
less noticeable several months postpartum
three distinct anatomical uterus types
duplex uterus
two cervical canals that separate each uterine horn into distinct compartments
two types
advanced duplex (marsupial (opossum, kangaroo)
single vaginal canal opening to the exterior
in the interior, bifurcates into two vaginas and two cervices
two cervices, two (three) vaginas, two uterine horns
duplex (rabbits, mouse)
two uterine horns, two distinct cervical canals connected to a single vaginal canal
able to deposit semen of two studs into separate horns
produce two sets of offspring with different genetic types
one vagina, two cervices, two uterine horns
bicornate uterus
two uterine horns, small uterine body
uterus opens into vagina through a single cervical canal
internal and external uterine bifurcation of horns can be distinguished
length of uterine horns dependent on degree of fusion between the paramesonephric ducts in developing female fetus
high degree of fusion
mare
short uterine horns, relatively large uterine body
moderate degree of fusion
cow, ewe, goat
uterine horns of intermediate (smaller) length
one vagina, one cervix, smaller uterine horns
little fusion
sow, bitch, queen
long uterine horns
mare and cow
poorly to moderately developed uterine horns
bitch, queen, sow
highly developed uterine horns
sow
two long uterine horns (litter bearing), common uterine body, one cervix, one vagina
simplex uterus
single uterine body
primates (humans)
small rudiments of a uterine horn structure, no uterine horns
almost complete fusion of paramesonephric ducts
resulting in single-chambered uterus without horns
no uterine horn, all uterine body
uterine environment
estrogen
increase vascularity
thickening of the uterus endometrium
stimulates growth of endometrial glands
progesterone
cause endometrial glands to coil and branch
to secrete histotroph “uterine milk”
nutritive material derived from maternal tissue other than the blood, utilized by the early embryo
Oviduct (Salpinx)
connects uterus to ovary
main functions:
final maturation of gametes
fertilization of oocyte
transport and facilitate early embryo and egg development
after fertilization, zygote remains at AIJ for 2-5 days (cow), until lumen of isthmus dilates to allow passage into uterine horn
muscular contractions move embryo into uterus very rapidly
embryos held in oviduct allow time for uterus to prepare for implantation
reduce sperm numbers to prevent polyspermy
ligaments contract
mesovarium supports ovary
mesosalpinx supports infundibulum and oviduct
transport oocyte to site of fertilization
ampullary cilia and infundibulum fimbria
provide proper environment for oocyte, sperm and fertilization
secretions from ampullary epithelial cells help prepare sperm for fertilization (capacitation)
secretions stimulated by estrogen are unique to estrus phase of cycle
two portions (in Stein’s world)
isthmus
smaller diameter, very muscular
few folds and few ciliated epithelium in lumen
serves as a sperm reservoir until it is released to AIJ
connected directly to uterus
uterotubal junction (UTJ)
point of uterine junction
functions to block polyspermy
in the cow
regulate movement of embryo into uterus
high estradiol → UTJ forms kink
blocking movement of embryos
decreasing estradiol → UTJ unkinking, straightening
isthmus lumen no longer blocked
thus, embryos can enter uterine lumen
in the sow
constriction of UTJ serves as a major barrier
to sperm transport
prevents excessive number of sperm from reaching ampulla
important in the prevention of polyspermy
other species
oviduct attaches to uterus without a kink-like constriction
ampulla
occupies 1/2 or more of oviductal length
site of fertilization
merges with isthmus of oviduct
large diameter, not very muscular
internal portions
many fern-like mucosal folds with ciliated epithelium
ampullary-isthmic junction
point of ampulla and isthmus junction
generally ill-defined
site of fertilization
in the mare
A-I junction serves as a control point
allows only fertilized oocytes to pass into isthmus, thus uterus
Fate of Unfertilized Oocytes:
sow, cow, ewe, doe
UFO will pass from oviduct into the uterus
mare
UFO will not pass into the uterus
embryos will bypass unfertilized oocytes and pass into the uterus
UFO’s will be resorbed
infundibulum (not technically part of the oviduct in Stein’s World)
terminal end of the oviduct
delicate, membrane-like component in close apposition to ovary
funnel-shaped opening
forms a pocket that “captures” the newly ovulated oocyte
directs ovulated oocyte into the oviduct
cumulus oophorus cells surrounding ovum aids in pick-up by the fimbria lining the infundibulum
surface covered with many velvety, finger-like projections (cilia)
fimbrae
greatly increase surface area of infundibulum
beat towards the opening of ampulla
cause it to glide or slip over entire surface of ovary near time of ovulation
this maximizes chance that oocyte will be “captured” after ovulation and transported through an opening
ostium
opening from infundibulum and ampulla
layer functions:
muscularis layer
transport newly ovulated oocytes and sperm to site of fertilization (ampulla-isthmic junction)
spermatozoa and ova move in opposite directions to meet at AI Junction
Isthmus
contractions toward the ovary
some sperm will continue out through oviduct
Ampulla
contractions and beating of cilia towards the uterus
mucosal layer
secrete substances
provide optimum environment for the free-floating, unfertilized oocyte
sustains spermatozoal function until oocyte arrives after ovulation
epithelium produce substances to support fertilizing capability of sperm
after fertilization, houses newly formed zygote
for a few days, before entering uterus
composition of fluid secretions from oviductal epithelium vital to providing suitable environment for development of early embryo
cilia on fimbria come in contact with COC and occyte
Ovary
egg-shaped, dense, turgid structure
easily palpated via rectum
cow, mare, camel
exocrine functions
female gamete production (ova)
house oocyte
diploid (2N)
endocrine functions
hormone production
estrogen
produced by follicle
secondary sex characteristics
progesterone
produced by corpus luteum
prepares uterus for pregnancy
steroid hormone
required for maintenance of pregnancy
size and shape between species:
cow
30 x 20 x 40 mm
oval shaped
queen
15 mm
round shaped
sow
35 mm
lobulated
mare
50 x 40 x 25 mm
kidney shaped
structures
germinal epithelium
named from the original belief of this is where germ cells were produced
single layer of cuboidal cells, serosal layer
continuous with peritoneal lining
prevents adhesions, does not produce germ cells, ruptures at ovulation
responsible for over 85% of ovarian events in humans
tunica albuginea
layer beneath the germinal epithelium
made of dense white connective tissue
provides structure to the ovary
ovarian cortex
houses the population of oocytes (germ cells)
cells surrounding oocytes will develop and produce follicles that will mature and eventually ovulate
oocytes within follicle
follicles produce estrogen
forms corpus hemorrhagicum, which luteinizes to form →
corpus luteum produces progesterone
degenerating CL = corpus albicans
ovulation occurs at random locations on the exterior of the cortex
everything BUT the mare
houses the:
functional corpus luteum
relatively large, visible structure
produces progesterone
can be palpated in the cow
degenerating corpora albicans
visible in most species
white, scar-like structure
represent corpus lutea in various stages of degeneration from previous estrous cycles
white from increasing ratio of connective tissue to secretory tissue
as corpus luteum degenerates undergoes a gradual transition from orange/yellow to white scar-like structure
ovarian medulla
houses the vasculature, nerves and lymphatics
supports cortex
made up of dense connective tissue
the mare’s ovarian cortex and medulla
cortex and medulla are reversed
cortex inside, medulla outside
function does not differ
ovulation only occurs at one location in the ovary
ovulation fossa
can’t superovulate because there is no space
follicles can be palpated per rectum in mare, but not corpus lutea
corpus lutea do not protrude from ovarian surface but penetrate into ovarian tissue
CL is internal because the cortex is internal
Oocyte and Follicular Development
Follicle Development
General:
located in the cortex
various types represent different stages of follicular development and maturity
four main stages, undergo:
foliculogenesis
process of immature follicles develop into more advanced follicles, to eventually be candidates for ovulation
atretic follicle
degeneration of a follicle
granulosa cells are fragmenting
cloudy appearance
Stages
primordial follicles
microscopic
most immature, smallest of all
oocyte surrounded by a single layer of squamous cells
stored, for recruitment
immature and smallest follicle in the cortex
primary follicle
“resting stage”
developed as a slightly more advanced primordial follicle
oocyte surrounded by simple cuboidal epithelium or follicular cells
stage of the majority of follicles
do not divide into other primary follicles
either develop into secondary follicles or degenerate
secondary follicle
developed as a more advanced primary follicle
oocyte surrounded by more than one layer of follicular (granulosa) cells
no antrum
follicular fluid-filled cavity
oocyte surrounded by the zona pellucida
relatively thick, translucent layer
antral follicle
blister-like structure, varying in size
size depends on stage of development or regression, and species
contains an antrum
differentiation of several distinct cell layers in the follicle wall
produces estrogen
also referred to as a tertiary follicle
graafian follicle
a tertiary follicle that is the dominant preovulatory follicle
unknown as to what makes a dominant preovulatory follicle
in cattle, sheep and horses
develop in sequential waves during both the follicular phase and luteal phase of the cycle
in primates, pigs and rodents
only develop during the follicular phase of the cycle
some are able to be observed with naked eye
on surface of ovary
three distinct layers
theca externa
composed of loose connective tissue
completely surrounds and supports follicle
theca interna
directly below theca externa
cells are responsible for production of androgens under the influence of lutenizing hormone
granulosal cell layer
also called membrana granulosa
beneath theca interna
separated by a thin basement membrane
produce variety of materials and have follicle stimulating hormone receptors
estrogen, inhibin, follicular fluids
FSH stimulates growth of follicle
govern the maturation of oocyte
Follicular Components
Stroma
includes more general components:
immune cells, blood and lymphatic vessels and nerves
Thecal Cell Layer
Theca Externa
line the outside layer of the follicle wall
provides structural integrity and support
composed of connective tissue and blood vessels
Theca Interna
outside the basement membrane of an antral follicle
middle layer of cells on the follicle wall
LH receptors here
produce testosterone under the influence of LH
converted to estrogen by granulosa cells
(two-cell theory)
Basement Membrane
separates the theca interna from the granulosa cell layer
Granulosa Cell Layer
line the inside of the follicle wall, surround the oocyte
support and control oocyte development
immature: contains FSH receptors
mature: contain FSH and LH receptors
LH and FSH are released from anterior pituitary
(tonic and surge)
two-cell theory: produce estrogen from testosterone
released with the oocyte during ovulation
important for maturation and transport in the oviduct
Hillock
stalk of granulosa cells supporting the ovum
Cumulus Oophorus (COC cells)
_______ cells surrounding the _
layer of cells outside of the Zona Pellucida
released with oocyte in/after ovulation
important for __ in the oviduct
a determining factor in oocyte selection for IVF
inhibit oocyte maturation
for fertilization to occur, the communication between COC cells and oocyte must be broken
“cumulus expansion” in oviduct
Corona Radiata
a single layer of granulosa cells
in direct contact with the zona pellucida of the oocyte
attaches cumulus cells to the zona pellucida
Zona Pellucida
a thick, translucent mucoprotein surrounding the oocyte and early embryo
Antrum
a cavity that contains follicular fluid
serum-like (liqour folliculi)
Two Cell Theory
“2-Cell, 2-Gonadotropin Model” for Estradiol Synthesis
Cholesterol(C27) → Progesterone(C21) → Testosterone(C19) → Estrogen(C18)
aromatase: enzyme converting testosterone to estrogen
Steps
Theca Interna Cells
produce testosterone
contain receptors for LH from the blood
the binding of LH initiates a cascade of intracellular events
net effect is conversion of cholesterol to testosterone
LH → cAMP → protein kinase (progesterone) takes cholesterol → testosterone
androstenedione is a weak androgen and is technically testosterone in this case
causes hair growth in women: axillary and pubic
testosterone then diffuses out of theca cells to granulosa cells
Granulosa Cells
produce estrogen (estradiol)
contain receptors for FSH from the blood
binding of FSH causes the conversion of testosterone to estradiol
FSH → cAMP, → protein kinase (aromatase) takes testosterone → estradiol
estradiol to blood capillaries
Estradiol
predominant estrogen produced b dominant follicles during the follicular phase of the estrus cycle
estradiol targets after diffusion into blood capillaries
brain
increase lordosis, phonation, physical activity
reproductive tract
increase blood flow, edema of tissues, secretions (mucus), leukocytes, smooth muscle motility, growth of uterine glands
increases blood flow (hyperemia) to all the organs
facilitates secretory activity
allows for delivery of leukocytes into submucosal region of RT (leukocytosis)
so invading foreign materials(including sperm) are engulfed after copulation
swelling of vulva (from elevated blood flow)
BRCA1 and BRCA2 are genes encoding DNA repair proteins
their mutants predispose a person to breast cancer
especially in the presence of estradiol
which is anti-apoptosis
Ovulation
definition:
release of an egg(s) from an ovary
from follicle rupturing
Steps Prior to Ovulation:
surge of LH
resume meiosis
collagenase causes the basement membrane to deteriorate
collagenase: causes the breakdown of collagen (major component of CT)
gap junctions between the granulosa cells and oocyte deteriorate
cells begin to intermingle
before meiotic resumption
they physical separation between Theca (interna) and Granulosa cells become incomplete
ovulation of antral follicles caused by surge of LH
small blood vessels rupture
causing local hemorrhage
can be seen by naked eye
During Ovulation:
loss of follicular fluid from antrum
causes walls of follicle to collapse into many folds
implosion
collapsed follicle contains blood, lymph, granulosa and thecal cells
granulosa and theca layers pushed to the apex of the follicle
theca interna and granulosa cells mix together
After Ovulation:
formation of a corpus hemorrhagicum
blood clot forms (blood filled “follicle” cavity)
walls
theca interna and granulosa cells mix together
basement membrane constitutes the connective tissue
luteal phase begins during formation of the corpus hemmorrhagicum
Types of Ovulators:
Induced
species - rabbit, cat, alpaca, camel, lion
cat:
tomcat has penile spines on glans penis to stimulate ovulation in the female
alpaca:
the seminal fluid (ovulation-inducing factor) stimulates ovulation in the female
lioness:
mates up to 100 times a day
average interval between mating: 17 minutes
each mating lasts for: ~21 seconds
Spontaneous
species- cow, sow, ewe, mare and woman
ovulation controlled by events of the hormone cycle
not affected by intromission
Luteal Phase
Definition: phase of the estrous cycle characterized by progesterone dominance and the presence of a functional corpus.
begins after ovulation and ends after lysis of the corpus luteum
luteal tissue is composed of luteal cells that originate from granulosa and thecal cells
consists of :
luteinization
synthesis and secretion of large quantities of progesterone
luteolysis
The Four L Words:
Luteinization
process where granulosa and theca cells are transformed into luteal cells
governed by luteinizing hormone (LH)
Luteotropic
a material having a stimulating action on the development or assisting in the maintenance of the CL
LH is a luteotropic material
Luteolysis
process where luteal tissue undergoes regression and cell death
(CL dies)
Luteolytic
a material that promotes luteolysis
ex. PGF2a (prostaglandin)
PGF2a plasma clearance in cattle was fivefold greater than in mares
mares = 1/5 dose of PGF2a as cows
Corpus Hemmorrhagicum
definition: a small, blood clot that results from rupture of blood vessels during ovulation
“bloody body”
appears immediately after ovulation
is a local hemorrhage resulting from the rupture of many small blood vessels
vascular breakage from ovulation
appears as a blood clot on the surface of the ovary
small, pimple-like structure
the basement membrane forms the connective tissue substructure of the CH to then form into the CL
in cows, process from which a CH turns to a CL takes 5 days
Corpus Luteum
definition: an orange, yellow or white colored transient endocrine structure formed after ovulation from granulosa and thecal cells of the ovarian follicle. responsible for producing progesterone an oxytocin. originates from an ovulatory follicle
forms from the corpus hemmorrhagicum and is developed via luteinization
during formation, the CL increases in size and loses its hemorrhagic appearance
increases in mass until the middle of the cycle
when size is maximal and coincides with the maximum secretion of progesterone during diestrus
the basement membrane forms the connective tissue substructure/network
in some instances, there is a remnant of the follicular antrum that forms a small cavity in the center of the CL
cow and mare: yellow color
sow and ewe: white color
CL Vigor
depends on:
number of luteal cells
the degree to which the CL becomes vascularized
cells of theca interna and granulosa cells differentiate into luteal cells
large luteal cells (LLC)
formerly granulosa cells
contain FSH and LH receptors
LH only at maturity
produce progesterone
contain a PGF2a receptor
necessary for actual prostaglandin
produces relaxin
produces oxytocin
signals for PGF2a to be released from the uterus
also produced by hypothalamus
during luteinization:
undergo hypertrophy
total number of granulosa cells determine the CL’s steroidogenic potential
small luteal cells (SLC)
formerly theca interna cells
contain LH receptor
produce progesterone
during luteinization:
undergo hyperplasia
contain fibroblasts around steroidogenic cells
Progesterone:
caps the surge → ovulation will not occur → maintains homeostasis
responsible for:
inhibits estrus and parturition
blocks myometrial contractions
stimulating endometrial secretion of nutrients for embryo
indirectly stimulating the production of a luteolytic agent
if no embryo present → prostaglandinF2a to regress the CL
decreases basal GnRH amplitude and frequency
blocking the preovulatory surge of luteinizing hormone
GnRH- Gonadotropin Releasing Hormone
releases LH and FSH
Progesterone is an inhibitor because it:
reduces GnRH pulse frequency
prevents behavioral estrus
stops the preovulatory LH surge
reduces myometrial tone
except in the mare
Corpus Albicans
regressed or degenerated corpus luteum
causes a drop in blood progesterone
composed of connective tissue (scar tissue)
no function
white, scar-like structure
continues to get smaller under no longer visible
luteolysis results in:
cessation of progesterone secretion
structural regression to form a corpus albicans
removal of negative feedback by progesterone upon GnRH secretion
resulting in a new follicular phase
PGF2a Control of Luteolysis
Uterus releases PGF2a
controls life of the CL
PGF2a is rapidly metabolized in some species
vasoconstrictor
cow (~90%) and pig (~40%) destroyed in one passage through pulmonary system
delivered to ovary to regress CL
Evidence of counter-current circulation pattern
exchange between vein and artery
PGF2a synthesis by uterine endometrium is released into Uterine Vein
PGF2a diffuses from the utero-ovarian vein into the ovarian artery
moves into artery → through counter-current exchange
PGF2a pickup up by ovarian artery and delivered back to ovary
causes lysis of CL
During pregnancy
embryo produces chemical signals to either…
inhibit PGF2a production
release to prevent CL death
sow, cow & ewe
artery is very close to vein
very tortuous
increasing contact between vein and artery
progesterone from CL stimulates production of uterine PGF2a after day 15 in the cow
mare
ovarian artery is straight and caudal to the vein
limited contact area between vein and artery
ewe example:
in the intact uterus
CL lifespan same as in normal cycle (5-17d)
total uterectomy
CL lifespan similar to normal gestation length (148d)
no PGF2a produced
partial uterectomy (contralateral to CL)
CL lifespan similar to a normal cycle (15-17d)
partial uterectomy (ipsilateral to CL)
CL has a longer lifespan than normal (35d)
Oocyte Development/Functionality
Background
females are born with a defined number of oocytes
no regeneration
germinal vesicle
the nuclear membrane around the chromosomes
ooplasma: oocyte cytoplasm
vitelline membrane: cell membrane around oocyte
last mitotic division completed close to time of birth
germ cells become located in gonad as the embryo/fetus develops
differentiate in fetal ovary
proliferate to form female germ cell population
primordial = first created
stages:
primary oocyte → secondary oocyte → ootid (haploid) → zygote
Cell Division (Meiosis I & 2)
phases of cell division
prophase, metaphase, anaphase, telophase
meiosis I
begins during fetal development
stops in prophase I
DNA enters resting stage (dictyotene)
can last for several years
oocyte is in meiosis I until ovulation
ovulation is a result of completion of meiosis I
cow ovulates secondary oocytes
mare and bitch ovulates primary oocyte
meiosis II
begin following ovulation
secondary oocyte + 1 polar body
polar body removes excess DNA
expulsion of first 1/2 of meosis I
not complete until egg is fertilized
secondary oocyte will stop in metaphase II until fertilization occurs
when fertilization occurs, meiosis II will resume and be completed
completion of meiosis II produces an → ootid + 2nd polar body
ootid contains 1 male and 1 female pronuclei
when male and female pronuclei break down nuclear membranes and DNA comes together (fuses) a zygote is formed
Oocyte Development
primary oocyte (2N)
single-cell
the largest cell of the body
~180mm
suspended in dictyotene stage during Prophase I of Meiosis I since birth
mare ovulates primary oocytes
Secondary Oocyte (1N)
1 polar body present
completion of Meiosis I
MI completed at time of ovulation
2nd stage of oocyte (meiotic) arrest
MII suspended in Metaphase II
completion just prior to/at time of fertilization
Ootid
oocyte after meiotic divisions in which polar bodies are present
2 polar bodies are present
2nd polar body is released to remove “excess DNA”
mature ovum after penetration by sperm but before the formation of a zygote
i.e. before the fusion of the male an female pronuclei
Zygote
diploid cell resulting from the fusion of the male and female pronuclei
one cell organism
Timeline of Oogenesis
Cattle:
birth: 50,000 to 100,000 oocytes/ovary
puberty: 20,000 to 30,000 oocytes/ovary
2 yr. old: 5,000 oocytes/ovary
Human:
midway through gestation: 6 to 7 million oocytes/ovary
birth: 1 to 2 million oocytes/ovary
puberty: 30,000 oocytes/ovary
37 yr. old: 25,000 oocytes/ovary
atresia rate increases
Follicular/Ovarian Cyst
a follicle greater than 17mm to 25mm in diameter
usually accompanied by one or more other large follicular structures
no CL is present
persist at least 10 days in the absence of a CL
very thin walled
a follicle becomes cystic when:
it fails to ovulate
and persists on the ovary
common signs an animal may be cystic
anestrus → lack of standing heat
abnormal estrous behavior patterns
including persistent estrus or shortened estrus intervals
dairy cattle and cystic follicles
incidence rate: 2.7-30%
peak incidences between 14-40 days postpartum
70% occur between 16-50 days postpartum
highest occurrence between 30-40 days postpartum
before day 16 and after day 50 postpartum = lowest incidence of ovarian cysts
causes:
stress
usually in high producing dairy cows
seasonal changes
altered hormone patterns
higher incidence during winter
genetics
can select against
other
retained placenta, milk fever, uterine infection, twins, etc.
what happens:
hypothalamus, pituitary and or an ovarian malfunction
insufficient LH released to cause ovulation
low levels of GnRH released
ovary does not respond well to LH
effects/treatment:
grow & regress (repeatedly)
causes nymphomania and short cycles
what is needed: increased LH levels to make cysts ovulate
administer GnRH to increase LH level
follow with PGF2a ~9 dyas later to regress luteal cyst
luteal cyst:
thick walled luteal tissue
CL with a fluid-filled cavity
not a problem with cyclicity…
LH induces luteinization of follicle wall, high levels of progesterone are produced and anestrus occurs
give PFG2a to make cysts regress
multiple transitional follicles
cystic ovaries in mares do not occur as often as dairy cows
the presence (or absence) of cystic ovaries in the mare, as described in dairy cattle has been a subject of debate for years