Reproductive System Flashcards
What is sex?
Need 2 individuals
produce germ cells which fuse to produce offspring
What is a characteristic of early fetal life with regards to the gonads?
during early fetal life, gonads are undifferentiated
How does embryonic sex differentiation occur?
Primordial germ cells form, which circulate in vasculature, and migrate through the tissues, they colonize on the genital ridge to form indifferent gonads
main form of differentiation - gene differentiation
- expression of genes in area of Y chromosome (sex determining region)
- testis differentiation factor is the gene that develops the testis
- default is female
What parts do testis and ovaries originate/differentiate from?
cortex -> ovary
medulla -> testis (through transient expression of genes testis differentiation factor (TDF) coming from sex determining region Y (SRY))
What is the main difference between the two chromosome composition for males and females?
Male - XY
Female - XX
What is specialized about birds chromosomes?
In males it is two XX’s and in females it is XY’s
TDF?
testis differentiation factor is the gene that develops the testis, female is the default
What is located beside the genital ridge?
Wolffian duct (will turn into male organs)
Mullerian duct (will turn into female organs)
Are both ducts present beside the genital ridges before differentiation?
Yes, both the wolffian duct (male) and mullerian duct (female) are present in the embryo initially
In what case is TDF not expressed (in the case of a female)?
If there is no Y chromosome, TDF is not expressed
Draw the main diagram from repro I
Draw
Refer to slides
How many/what are the centers does the hypothalamus have that contain GnRH neurons?
2 centers
Tonic center: basal secretion of GnRH
Surge center: ovulatory cycles and female behaviour
During sex differentiation in the perinatal period, what happens in the brain for both females and males?
Males:
Estradiol is released by the placenta and embryonic adrenals, the estradiol binds to carrier in the blood and doesn’t enter the brain
Testosterone is released by the embryo testes diffuse into the brain where it is converted to estradiol
Presence of estradiol in the brain inactivates the surge center = male brain
Females: No presence of estradiol (since testosterone is not being produced and it cannot convert to estradiol since it doesn’t exist) the surge center will remain
What is the major function of the male reproductive system?
Produce and deliver spermatozoa to the female
What are the testis the site of?
Spermatogenesis
What is the function of the epididymis?
Final maturation of sperm, stored in tail of epididymis
What is the sperm mixed with?
Excretion of accessory glands and delivered out of the penis into the female reproductive tract
Draw out the steps to overall sperm production
refer to slides Repro II
What is the ideal temperature for testes?
Need to be kept 4-6 C below core temperature for spermatogenesis (why they hang out of the body)
When are testes dropped?
during late gestation or early life
How are testes dropped?
drop via inguinal canal in scrotal sac, some cases where testes cannot descend due to malfunction in these things
How are the testes temperature controlled in later life?
controlled by veins of the pampiniform plexus (in spermatic cord) forming a countercurrent heat exchanger, veins wrapped around the arteries to lower temperature
Where are testes located?
scrotum
What is the scrotum?
Skin sac from the abdominal cavity with a layer of smooth muscle (tunica dartos)
What is present on the inside of the scrotum?
Layers of connective tissue (scrotal fascia and parietal vaginal tunic)
What is covering the testes?
A layer of vascularized connective tissue (tunica albuginea and visceral vaginal tunic) that projects septa in the testes, smooth muscle cover the septa (help move immature sperm)
What are the ways of moving the testes closer or further from the body to maintain temperature?
Under skin (tunica darcas) - smooth muscle that will contract/relax to move the testes
In between parietal/visceral vaginal tunic that allows for further movement
Where are seminiferous tubules located?
Lobule of the testes
Label the testes diagram
slide 10 of repro II
What are the two major parts of the testes
seminiferous tubules and the interstitium
What are the seminiferous tubules?
Site of sperm production. Ducts collect sperm to rete testis in the center = tubes that bring the sperm to the epididymis
What is the interstitium (between seminiferous tubules)
composed of connective tissue, nerve, blood vessels, and leydig cells which produce testosterone
Label the sperm transitioning between the interstitium and seminiferous tubules
Slide 12 Repro II
What are the differences between a boar reproductive tract?
- testis structure similar to bull - more pronounced interstitium (leydig cells produce wider array of angrodens plus estrogens)
- testis location against the abdominal cavity reduces efficiency of heat exchange
- large seminal vesicles - large volume of ejaculate
- large bulbourethral glands - gel portion
- copious ejaculate - prolonged ejaculation
- smaller sperm reserves
Label the male repro diagram
slide 16 repro II
understand the diagram showing the multiplication of cells during spermatogenesis?
slide 21 repro II
What are the steps to meiosis?
- interphase: replication of DNA
- prophase I
- leptotene: condensation of chromatin
- zyogotene: pairing of homologues (forming tetrad)
- pachytene: crossing-over and recomb
- diplotene: synaptonemal complexes dissociate
- diakinesis: chiasma disappear and homologues begin to repel
- metaphase I: homologue centromere binds to spindle fiber
- anaphase I: homologous pairs separate and begin to move
- telophase: chromosomes migrate to each pole, cell division. 1 chromosome of pair in each cell
- prophase II: spindle fibers rearrange and chromosomes recondense
- metaphase II: chromosomes align along spindle equator
- anaphase II: sister chromatids separate and move to opposite poles
- telophase II: daughter cell nucleus has one set of chromosomes
What is the function of sertoli cells?
blood testis barrier. provide nutrients and several factors to control spermatogenesis
pump fluid during final maturation of sperm
What is a specialized feature of sertoli cells?
basal/luminal and adluminal compartments
What do sertoli cells produce?
androgen binding protein and inhibin
What do sertoli cells express?
FSH receptors (regulated by FSH)
What is spermiogenesis in contact with?
sertoli cells
What are the steps to spermiogenesis?
- nuclear condensation
- formation of the acrosomal cap (derived from golgi)
- development of a tail
- the distal centriole provides a template for accretion of cytoskeletal elements comprising the contractile lattice of the tail
- mitochondria become concentrated into the sheath of the middle piece
Label the sperm diagram
Slide 29 repro II
What are leydig cells where are they located?
interstitial cells that are highly perfused - located in the spaces between tubules
What do leydig cells synthesize
androgens - testosterone
What do leydig cells express
LH receptors
What are the stages of the motility of the sperm in each part of the pelvic urethra?
Head of the epididymis: immotile infertile
Body of the epididymis: Acquisition of potential to be motile fertile
Tail of the epididymis: upon dilution the sperm are motile and fertile
Sperm in which part of the tail of epididymis can be transported to ejaculatory position?
Distal tail
What are the accessory glands of the male reproductive tract?
Ampular gland, vesicular glands, prostate, bulbourethral gland
What is function of ampular gland?
Absent in boar/dogs, elargement of the ductus defferent
What does the vesicular gland secrete?
Fructose (sperm energy), vitamins and prostaglandins (motility and survival), proteins for coagulation
What does prostate gland secrete?
alkaline substance to enhance motility
What does bulbourethral gland secrete?
Alkaline substances to neutralize acidity and mucus to lubricate vagina during copulation
How many days does it take for spermatozoa to be transited through the system?
Spermatocytogenesis (spermatogonia to spermatids) - 47 days
Spermiogenesis (spermatid to spermatozoan) - 14 days
Spermatogenesis - 61 days (4.5 cycles)
epididymal transit - 10-12 days
What are the steps to arousal?
- sensory stimulation (optic, olfactory, tactile and auditory)
- stimulation of nerves in the supraoptic and paraventricular nuclei
- release of oxytocin from the posterior pituitary
- contraction of smooth muscle in distal tail of epididymis and ductus deferens
- transport of spermatozoa into an ejaculatory position
What are the steps to ejaculation?
- intromission
- sensory stimulation of glans penis (temperature and pressure)
- sudden and powerful contraction of urethralis, bulbospongiosus and ischiocavernosus muscles
- expulsion of semen
What are the ingredients used for cryopreservation of ejaculate?
Nutrient
- egg yolk
- whole homogenized milk
Buffer
- citrate
- sodium phosphate
Antimicrobials
- penicillin/streptomycin (bacteria)
- minosin (mycoplasma)
Cryoprotectant
- 6-12% glycerol (if to be frozen)
Draw out the endocrine control in the male reproductive system?
slide 44 repro ii
What is the structure of GnRH?
decapeptide
How is GnRH released, how does it travel?
Released in a pulsatile manner in the median eminence
Travels via the portal blood system to the anterior pituitary
What is the end of the feedback loop for GnRH?
In the hypothalamus, GnRH neurons receive information about internal and external stimulus
What type of receptor are GnRH receptors? and how do they work?
G protein-coupled receptors, upon binding, can stimulate both Galphaq and Galphas, in pituitary, leads to release/synthesis of gonadtropins (LH and FSH)
What tissues are GnRHRs present in?
Pituitary, ovary, prostate and placenta
What type of proteins are LH and FSH?
glycoprotein hormones composed of 2 subunits: common alpha subunit and specific beta subunit
What are LH and FSH produced by?
Gonadotropes
What are the characteristics of the LH receptor?
G protein coupled receptor
activates Galphas = increase in cAMP
binds both LH and hCG
What are the characteristics of the FSH receptor?
G protein coupled receptor signaling via Galphas
What type of protein is inhibin and activin?
glycoprotein composed of 2 subunits
What is inhibin produced by?
sertoli cells in males and granulosa cells in females
What does inhibin inhibit?
FSH
What does activin stimulate?
FSH
What do inhibin and activin act in conjunction with?
GnRH
What are gonadal sex hormones derived from?
stepwise conversion of cholesterol, lipophylic with nuclear (intracellular) receptor
What does the steroid derivation into sex hormones depend on?
Type of steriod depends on the presence of specific enzyme substrate in the cell
What is the stepwise conversion of estradiol?
Pregnenolon
Progesterone
Testosterone
Estradiol - aromatization of the ring by the enzyme aromatase
What are the type of receptors used in steroids?
NHRs. effect on gene transcription
How many target organs are there for sex steroids?
Many target organs, since steroids diffuse in virtually any cell of the body receptors are widely distributed
What type of receptor does testosterone use?
androgen receptor
What are the receptors for estrogens?
2 receptor types:
ERalpha - stimulates txn
ERbeta - inhibits txn
main difference - locations, effects of drugs will depend on ability to bind and activate ER alpha or ER beta
What is a specialized feature of estrogen receptors?
receptors require coactivators/regulatory molecule to mediate their actions on target gene promoters
What is the missing link in the GnRH loop?
Kisspeptin, GnRH neurons do not express ERs but kisspeptin neurons do
What are the external reproductive organs of the female repro system?
vulva and clitoris, heat signal
What are the internal reproductive organs of the female repro system?
Ovaries - oocyte formation
Oviducts - transport of oocyte + fertilization
Uterus - transport of spermatozoa, implantation, support for fetal development
Cervix - passage between uterus and vagina
Vagina - receptacle for male penis
What are the broad ligaments made of?
mesovarium + mesosalpinx + mesometrium = broad ligament
Label the female repro system diagram
Slide 4 repro IV
What are the external genitalia of the female repro system and what re their functions?
Labia major (female equivalent to scrotum) + labia minor = vulva
- closure that minimizes entrance to vagina
- labia can swell with blood during estrus (visual signal) (pigs/dogs)
Clitoris - erectile tissue equivalent to the male penis, high density of sensory nerve endings
Urethra opening
Vaginal opening
What is the main function of the vagina
Receive the penis during copulation, inner part is highly secretory (close to cervix)
Resident bacteria on surface secrete lactic acid, resistance to infection
What is the outer part of the vagina made up of?
stratified squamous epithelium resistant to mechanical stress, keratinization is some species
Label the diagram of the vagina
Slide 9 repro IV
What is the function of the cervix?
Marks the separation between vagina and uterus, regulates passage from/to uterus, protects fetus during pregnancy
What is the cervix made of?
Fibrous connective tissue with collagen and elastin + some smooth muscle
What is the cervix influenced by?
estrogen and progesterone
What kind of cells does the cervix possess?
mucus producing cells (help lubricate vagina), during luteal phase and pregnancy, mucus secretion decrease due to progesterone
Label the cervix diagram
slide 11 repro IV
What is the function of the uterus?
Transport spermatozoa to the oviduct
site of implantation (attachment), supplies fetus with nutrients and removes waste
protects and transports fetus during pregnancy
supplies information about pregnancy (endocrine)
structure varies between species
What are the three structural layers of the uterus
endometrium: mucus membrane
- high density of glands
- penetrating veins and arteries
- stratum basale and stratum functional (grow and shed during menstrual cycle)
myometrium: smooth muscle layers, regulated by ovarian hormones and oxytocin
perimetrium: connective tissue
Label the uterus diagram
Slide 14 repro IV
What are the functions of the oviducts?
collect the egg cell from the surface of the ovary
transport spermatozoa from uterus to site of fertilization
help spermatozoa final maturation for fertilization
transport embryo to the uterus
What are the 3 main sections of the oviducts?
infundibulum: funnel-like structure
ampulla: proximal part
isthmus: distal, narrow. contain smooth muscle and ciliated glandular epithelium
Label the diagram of the oviduct
slide 16 repro IV
Label the ovaries diagram
slide 18 repro IV
What happens to the gonad after initial differentiation?
Formation/activation of primordial follicles
What is the formation and activation of primordial follicles independent of?
Process is gonadotropin (LH/FSH) independent in mammals
How are primordial follicles formed?
Formation/activation of primordial follicles:
A large number of PGC (now oocytes) will die
Squamous granulosa cells start to differentiate
Oocytes organized in clusters surrounded by the squamous granulosa
oocytes start meiosis and arrest in prophase I
cysts break down and oocytes surrounded by a layer of squamous pre-granulosa cells = primordial follicles
once stimulated into a primary follicle the process is irreversible
this process results in significant oocyte death, this is a critical stage
What is the difference between a primordial follicle and a primary follicle?
surrounded by:
- layer of squamous pre-granulosa cells = primordial follicles
- layers of cuboidal granulosa cells = primary follicle
How are primary follicles formed?
- meiosis is arrested in the diplotene stage of prophase I
- during this arrest, chromosomes decondense and are actively transcribed = tremendous growth of oocytes
- membrane is seen surrounding oocyte which will become zona pellucida
- factors secreted by oocyte stimulate granulosa cells
- in turn, granulosa cells from primary follicle secrete factors which stimulate oocyte growth
What is a primary follicle defined by?
Simple cuboidal cells surrounding the oocyte
What occurs within the oocyte during its growth?
- replication of cytoplasmic organelles (especially mitochondria and their DNA)
- increase in ribosome, mRNA and proteins
- lots of nutrients stored in granules and vesicles
- golgi apparatus enlarge and moves to the periphery (export ZP glycoproteins; cortical granules)
- centriole disappears (the male one will be used)
How do the oocyte and granulosa interact during the primary follicular stage?
Granulosa cells start expressing FSH receptr and thus now responsive to FSH (critical point for growth/recruitment)
Communication via gap junctions between granulosa cells and oocyte critical to prevent meiosis to proceed
What happens during the formation of a secondary follicle?
- large increase in granulosa cell layers, surrounded by basal lamina
- theca cells start to multiply on outside of basal lamina
- internal theca
- external theca with muscular layer
- simultaneously blood vessels develop within the theca
- nutrients and waste will have to diffuse from the theca layer (no blood vessels within the follicle)
What occurs during the formation of antral follicle
- cavitation: appearance of a fluid filled cavity
- both granulosa and theca cells multiply
- theca external and theca internal form
What is the theca externa?
muscular innervated layer
What is the function of the theca interna
produces androgens under the control of LH
What are the four stages of antral follicles?
small medium large and preovulatory
What happens after small group of antral follicles form? (follicular wave)
- a group of small antral follicles grow and mature in synchrony = recruitment (growing follicles secrete estradiol and inhibin in increasing amounts)
- some follicle stop growing and undergo atresia the others keep growing = selection (inhibin levels rise = inhibits FSH production)
- dominant follicles have high density of FSH receptors and high sensitivity to FSH, continue growing to graafian follicle = dominance
Draw the diagram discussing the follicular wave
slide 19/20 repro V
How does the final maturation of oocytes occur?
diplotene -> diakinesis -> metaphase I -> anaphase -> telophase (polar body I) -> prophase II (short) -> metaphase II -> (ovulation) (sperm penetration) -> anaphase -> telophase (polar body II)
What happens when meiosis resumes after the halt of prophase?
- occurs during the ovulation sequence
1. germinal vesicle breaks down - LH stimulates local production of growth factors; including IGF
- LH surge desensitized granulosa cells = decrease in cAMP
2. completion of first meiotic division with expulsion of the first polar body
3. initiation of the second division with arrest in metaphase II until fertilization
What is cytoplasmic maturation essential for in the female repro system?
essential for monospermic fertilization, processing of sperm, preparation for development to preimplantation
What happens during cytoplasmic maturation?
- Ability to release intracellular Ca upon fertilization (triggers exocytosis of cortical granules)
- Production of proteins which will prepare female pronucleus
- accumulation of mRNA, proteins, substrates
What happens during ovulation?
- high concentration of LH (from surge) leads to:
- accumulation of fluid = increase pressure in the follicle
- secretion of collagenase = loosen
the ovarian connective tissue - increased blood flow in ovary, fluid
accumulates further
- secretion of collagenase = loosen
- accumulation of fluid = increase pressure in the follicle
- follicular wall bursts, oocyte released from granulosa cells, captured by the infundibulum, moved to ampula by ciliated epithelium
- LH surge:
- induction of COX-2 enzyme
resulting in local prostaglandin
production
- induction of COX-2 enzyme
- prostaglandins act on epithelial cells of the presumptive stigma:
- release of lysosomal enzymes
- degrades underlying tissue
- stigma formation and release of the mature egg cumulus complex
When does the luteal phase occur?
After ovulation
What happens in the luteal phase?
- after ovulation: corpus hermorrhagicum (granulosa and theca cells mix)
- corpus luteum: mixture of large (ex-granulosa) and small (ex-theca) cells
- produce large amount of progesterone: -ve feedback on GnRH
- invasion with blood vessels
Draw the graph of the menstrual cycle
slide 28 repro V
When does the oocyte encounter spermatozoa within the oviduct?
within 15-30 minutes of ovulation
How long after ovulation is fertilization still viable for different species?
Human: <24 hours
Pig: 20
Sheep: 15-24
Cow: 22-24
Mare: 24
What are some behaviours during estrus in cows?
- mounting
- Standing to be mounted (lordosis)
- chin pressing (testing)
- head-turning (welcoming)
- urine (vulval) sniffing (estrus related odours)
- restless/irritable/noisy (more active)
- escape
What is mounting /standing to be mounted in cows in estrus stimulated by?
mounting: stimulated by estradiol-17beta
standing to be mounted: requires more estradiol-17 beta (higher threshold)
What is a major cause of failed pregnancy in dairy cows?
failure to timely detect estrus
What are the steps in the neural pathway for mounting/estrus behaviours?
- sensory (visual, olfactory, auditory, tactile)
- hypothalamus: estrogen receptors, increase E2 which leads to increased nerve excitability, neurons produce behaviour specific peptides
- midbrain: receiving zone for hypothalamic peptides, speeds up impulses
- spinal cord: generates signals to specific muscles for lordosis and mounting
What are the factors promoting mounting behaviour?
- size of sexually active group (2+)
- time of day (night)
- footing (dirt, non slippery)
- age/health of cow (agility)
- head room (lots of it)
- lack of distractions/human activity
- temperate weather
What are some non-behavioural changes at estrus?
- copious cervical mucous discharged (watery/stringy)
- vulva reddening/swelling
- low progesterone
- high estradiol-17beta
- estrus-related odors
- LH/FSH surge
- met-estrus bleeding (cattle)
What are the steps to fertilization within the female system?
- immediate transport: retrograde loss, phagocytosis, entrance into cervix/uterus
- cervix: privileged pathways, removal of non-motile sperm, removal of some abnormalities
- uterus: capacitation initiated, phagocytosis
- oviduct: capacitation completed, hyperactive motility
- fertilization: acrosome reaction, spermatozoon penetrates oocyte, male and female pronuclei form
What is the first trap when sperm is transported into the female repro tract?
Cervical folds
- glands produce acidic mucus which prevents microorganism entry and also is a physical barrier (fold + mucus = plug)
During estrus, how is the mucus composition of the cervix changed?
E2 acts to change mucus composition
- less acidic
- thinner/more elastic
- forms strands to allow sperm to pass
after ovulation, P4 returns mucus to acidic barrier
How much semen is dosed during artificial insemination of cows?
20x10^6 spermatozoa
Where is semen deposited during AI of cows?
body of uterus (first AI)
anterior cervix (repeat AI)
What is the primary source of loss during AI in cows?
retrograde flow, wrong horn
What are the major reasons for failure during AI in cows?
cow not in heat
poor technique
early embryonic mortality
How do contractions in females occur in order to effectively transport sperm?
Mating -> nervous stimulation -> post pit -> oxytocin (milk ejection) -> increased contractions of uterus/oviducts favoured by high ratio E2:P4
How do sperm change (capacitate) when they enter the female tract?
- loss of surface proteins (acquired during epididymal transit) = reorganization of plasma membrane lipid composition
- hyperactivation of motility for final approach to oocyte
What is capacitation initiated by?
in uterus by the utero-tubal junction
What do sperm require after capacitation?
require intact acrosomes for acrosome reaction during fertilization
What is necessary for IVF?
in-vitro capacitation
What are some characteristics of the oviduct?
- internal mucosa and lamina propria well developed in the infundibulum and ampulla
- possess ciliated epithelium (under control of E2) beat and move fluid toward uterus
- secretory cells (peg cells) secrete nutrients for oocyte and antimicrobial
- smooth muscle layers
What are required for fusion of sperm to egg?
- penetration of the corona radiata (layer of granulosa cells)
- perforation in the zona pellucida = acrosome reaction
- transfer of the nucleus
What happens once the sperm reaches the egg?
- several sperms reach the corona radiata then release their enzymes to dissociate granulosa cells (sacrifice themselves)
- one lucky sperm reaches the zona pellucida
- membrane proteins on the sperm cell surface bind glycoprotein of zona pellucida: acrosomal reaction
What is the acrosome reaction?
- Release of enzyme = acrosome reaction (fusion of inner and outer acrosomal membranes)
- acrosin (trypsin-like) plus hyaluronidase released in close proximity to oocyte
- required to penetrate zona pellucida of oocyte
What happens to the acrosome reaction if there is no oocyte?
acrosome reaction occurs in a progressively larger portion of the population
Where does fertilization occur?
at junction of ampulla and isthmus
What are the steps to fertilization?
- oocyte arrives and loses cumulus
- hyperactivated spermatozoa passes through remaining cumulus
- binds to zona pellucida
- acrosome reaction
- penetrate zona (zona reaction)
- penetrates vitelline membrane
- loss of cortical granules
- extrusion of polar body 2
- syngamy
What happens after the sperm reaches the egg?
- As the sperm enters, oocyte completes meiosis, within 12h, both hapoloid pronucleus fuse to form a diploid fertilized egg = zygote
- after 4-5 days morula enters the uterus
- unattached embryo converts to blastocyst (inner cell mass will form the embryo, trophoblast will form the amnion and the chorion)
- cavity = blastocoele
What is a zygote?
Giant cell, divides every 24 h to form smaller cells = cleavage
Draw the graph with the luteal phase
slide 3 repro VII
What is the major steroid produced?
P4
What happens during the luteal phase?
- granulosa/theca cells luteinize and form corpus luteum
- steroid synthesis is truncated (loss of cytochrome P450 17 alpha and SCC) -> progesterone is final product
- initially, granulosa cells form large luteal cells which lack LH receptors and autonomously produce large amounts of P4
- Corpus luteum remains independent of LH for 6 days
- after this, corpus luteum becomes lH dependent with theca derived cells predominant, these start as small luteal cells, but differentiate to become large luteal cells and produce larger amounts of P4
- towards end of cycle, most luteal cells are large
PGF2alpha is luteolytic during most of last 2/3 of CL life
What do the large luteal cells contain towards the end of the luteal cycle?
oxytocin (in cytoplasmic granules), produce large amounts of P4, acquire surface receptors for prostaglandin F2alpha (PGF2alpha) beginning on d 5-6 post ovulation
What is endometrium development timed with?
cyclic changes in estradiol and progesterone
What are the three phases of the endometrium cycle?
proliferation phase: during follicular phase, estradiol stimulates growth of stratus functionalis
secretory phase: during luteal phase, progesterone stimulates development of uterine gland
mestrual phase: decrease in ovarian steroid induces the necrosis of stratum functionalis
Draw the diagram on slide 8 of reproVII
draw
What happens in the proliferative phase of the endometrial cycle?
- endometrium is divided into 2 layers, basale and functional
- glands are straight and narrow throughout entire length
- glandular epithelium starts to multiply
- spiral arteries system develops in the functionale
What happens in the secretpry phase of the endometrial cycle?
- glands are more tortuous
- spiral arteries extend to the epithelial layer
- glandular epithelium loaded with glycogen
What happens in the menstrual phase of the endometrial cycle?
- functional layer regresses, shrinks and atrophies
- super coiling of spiral arteries
- reduced blood flow = release of toxic and vasoactive substances
- vasoactive substances = physiological endometrial “infarction”
What are the hormones involved from the follicles?
estradiol released during follicular phase
ERalpha in endometrium = mitosis
progesterone during the luteal phase inhibits mitosis, stimulates mucus secretion form uterine glands and relaxes smooth muscle
What are the hormones involved coming from the uterus?
prostaglandins: local effect
PGF2alpha constricts uterine arterioles = anoxia
endometrium sloughed = menses start
Draw the diagram on slide 14 of repro VII
draw
What are prostaglandins?
PGF2alpha and PGE2
WHat are prostaglandins produced from?
PGF2alpha and PGE2 are locally produced from fatty acids
What are prostaglandins deactivated by?
dehydrogenase
What does Estrogen (E2) vs progesterone (P4) do
E2 stimulates COX wherease P4 inhibits it and stimulates inactivation
When does E2 receptor expression decrease and where?
E2 receptor expression decreases in the glandular tissue during secretory phase but remains in the stroma
What is the major site of production of prostaglandins?
basal layer
What do prostaglandins do when P4 levels fall?
PGF2lalpha and PGE2 released and diffuse into the spiral arteries = vasoconstriction and the myometrium = contraction
Draw the graph for the effect of PGF2alpha on the ovary and corpus luteum
slide 16 repro VII
Draw the different types of uterectomys
slide 17 repro VII
Draw the oxytocin receptor graph?
slide 18/19 repro VII
What causes cramps?
pulsatile release of oxytocin (post pit) drives pulsatile release of of PGF2alpha and increases the contractility in the uterus
What are the actions of exogenous PGF2alpha on luteal cells?
large cells: PGF2alpha receptors, produce 80-90% of total progesterone synthesis, contain oxytocin as cytoplasmic granules
small cells: LH receptors
What do injections of PGF2alpha do to luteal cells?
injection of PGF2alpha are luteolytic
- reduce blood flow to corpus luteum
- PGF2alpha binds to receptors on large cells to: release oxytocin by exocytosis, inhibit conversion of cholesterol to pregnenolone
- collateral loss of small cells
- cellular degradation
What are the maturation rates for each point in placentation? (days)
Morula -> (4days) blastocyst
blastocyst -> (7-8 days) endoderm
Draw the diagram of the oocyte-blastocyst travelling from the infundibulum to the uterus
slide 3 repro VIII
What is the oviduct length for pig, sheep/cow, mare?
Pig: 25 cm
Sheep/Cow: 20-30 cm
Mare: 30 cm
What is the transit time of the oocyte to the uterus for pig, sheep/cow, and mare?
Pig: 2 days
Sheep/Cow: 4 days
Mare: 6 days
What is the stage of the oocyte entering the uterus for pig, sheep/cow, and mare?
Pig: 4 cell
Sheep/Cow: morula
Mare: blastocyst
What is the attachment day of the oocyte to the uterus wall for pig, sheep/cow, and mare?
Pig: 13th day
Sheep/Cow: S14/C19
Mare: 40th day?
What part of the blastocyst becomes a fetus?
The inner cell mass
What parts of the inner cell mass will become a part of the fetal membrane?
trophoblast
What happens to the chorion after hatching?
chorion rapidly grows laterally (as a sheet 1 cell thick) to occupy space within the uterus, ICM will be in the middle and growth will occur laterally
What are the steps required for placentation of the fetus in the uterus?
Recognition (apposition)
Contact (adhesion)
Formation of a functional placenta (invasion)
- series of events
- genetic compatibility
- molecular and cellular aspects
What are the 5 things the conceptus must do during placentation?
- move to proper location in the uterus
- stimulate production of histotroph by endometrium (prior to attachment, embryonic synthesis of protein factors, steroid)
- prevent luteolysis (requires P4 dominated uterus: maintain it non-contractile)
- Inhibit maternal immune system
- Establish placenta (more definitive attachment, more effective transfer nutrients/waste between mother/fetus)
What is the rodents strategy for retaining luteal function during early gestation?
luteotrophin release by mating (LH/prolactin) (infertile mating can lead to pseudopregnancy)
What is the cow/sheep/sow/mare strategy for retaining luteal function during early gestation?
Antiluteolytic mechanism
What is the primates strategy for retaining luteal function during early gestation?
chorionic gonadotrophin (similar to LH, supports CL)
Draw the antiluteolytic mechanism for tau
slide 10 repro VIII
What cells play an important roll in luteolysis in bovine pregnancy?
uterine epithelial cells in the uterine horn on the same side as the CL bearing ovary
Where does oxytocin from the CL bind to?
bind to receptors in the uterus, this triggers the release of PGF2 alpha into the uterine vein, PGF2alpha is transferred to the ovarian artery, initiating luteolysis
Please draw the graph showing conceptus vs no conceptus present
slide 13 repro VIII
What is the double velcro analogy?
Nature of the chorionic attachment in bovine pregnancy
- mini velcro: microvillar interdigitation (important early)
- maxi velcro: chorionic invasion of endometrial glands (21-50 days, starting at embryonic disk)
- massive increase in surface contact area to facilitate transfer
Draw out the table for each type of placenta in species?
slide 19 repro VIII
What are the two types of caruncles and what species have which?
Convex caruncle (cow, giraffe)
Concave caruncle (sheep, goat)
What does an early embryo use instead of a placenta?
allantois, then placenta
What types of nutrients are transported across the placenta?
- water and lipid soluble substances diffuse across epithelium (including gases)
- AA, Ca2+ glucose and vitamins are actively transported
- FFAs diffuse more/less depending on species
What happens as the fetus grows in terms of glucose requirements?
As the fetus grows, need for glucose increases, digestive capacity of mother decreases, mother uses fat for energy = accumulation of ketone bodies (toxic)
What type of gland is the placenta?
endocrine gland
What hormones does the placenta release?
peptide hormones
- gonadotrophic hormones: stimulates CL
- lactogenic hormones (placental lactogen): stimulates growth of mammary tissue during pregnancy
- relaxin: produced by placenta and CL, with progesterone it prevents uterine contraction. before parturition, loosen the cervix connective tissue and pelvis ligaments
What is progesterone the key to?
maintaining pregnancy
How is progesterone made in the placenta?
from cholesterol
Where are trophoblast cells present?
in the placenta
What do trophoblast cells lack and how do they work around that?
lack the enzyme 17alpha-hydroxylase, so they cannot convert C21 steroids (like progesterone) into C19 steroids (precursors to estrogen)
instead, DHEA-S from the fetal adrenal glands is converted by trophoblasts into Estradiol-17beta near the end of pregnancy, supporting the hormonal changes required for birth
What is successful pregnancy dependent on?
Adequate progesterone concentration
What procedures or conditions will induce abortion?
Procedures or conditions that disrupt progesterone production
hypophysectomy
ovariectomy
lutectomy
luteolysis
antibodies against progesterone
Draw out the progesterone levels during different stages of pregnancy
slide 29 repro VIII
What is stage one of parturition?
- progesterone concentrations fall
- estrogen concentrations increase or remain unchanged
- pubic symphysis begins to relax, pelvis tips
- myometrial contractions intensify
- cervix softens and begins to dilate
What is stage two of parturition?
Labour
- cervical stimulation provokes oxytocin release, force/duration of contractions increase
- membranes rupture
- birth: vascular changes/lung maturation
What is stage 3 of parturition?
Delivery of afterbirth
What is the stimulus for parturition?
the fetus: once fetal hypothalamus is matured (CRF), anterior pit gland (ACTH), adrenal axis (cortisol)
fetus becomes capable of mounting - physiological response to stress (low pO2, low blood glucose)
Which fetuses are more difficult to birth?
Males take longer to birth as they are heavier and have a longer gestation
Explain the chart of the stimulus of parturition
Slide 11-15 repro IX
What are other effects of cortisol during parturition?
- lung surfactant synthesis
- circadian rhythms and birth time
- lactogenesis (+prolactin epinephrine GH T3IT4)
- fetal energy balance
- brown fat (+epinephrine)
What does the maternal side release if parturition is successful?
maternal glucocorticoid release
draw out the diagrams of cortisol release
slide 17/18 repro IX
What is an issue with natural birthing induction in cattle?
ruminants in late gestation will not always respond to PGF2alpha alone
What are the options to induce parturition in cattle who are having a hard time giving birth?
CRF
ACTH
Cortisol
Synthetic glucocorticoids: dexamethasone, 2-3 days from injection to labour
Maybe oxytocin???
What is a retained fetal membrane?
After delivery, placental separation should occur within a few hours.
in dairy cows, a small but significant proportion of animals retain membranes for days or even weeks
What is a retained fetal membrane associated with?
subsequent infection of the uterus
slow uterine involution
increased interval to first ovulation post partum
What are the causes of RFM?
- premature delivery
- low vit E/Se status
What is the treatment for RFM?
- essentially no treatment
- bag placenta in rectal sleeve
- monitor for infection + treat if necessary
- don’t pull or unbutton