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Differentiation
Process whereby a primitive group of unspecialized cells develop into functional, recognizable group of cells that have a common function
Embryonic germ layers (formed for first step of differentiation)
Endoderm (inner layer) guts lungs, liver
Mesoderm = muscle, skeleton, cardiovascular repro system
Ectoderm = nervous system, skin, hair
Mammals Sex
Chromosomal = XY (male) AND XX (female)
Gonadal Testis = Male, Ovary = Female (determination happens early on in the embryonogenesis/gestation)
Phenotypic sex= voice, breasts, fat deposition, hair patterns, other characterisitics
Behavioral Sex= Sex of the Brain
1st trimester
migration of primoridal germ cells from yolk sac, sex cords develop in gonad, paramesonephric ducts develop
sex evident from features
2nd trimester
development of male/female ducts, oviduct/testes
formation of broad ligament (half in 1st half in second for male/female ducts)
3rd trimester
testicular descent (before partiution) sooner for bull and ram (more like 2nd trimester) very late for colt
Formation of anterior and posterior pituitary glands
Diverticulum = sac/pouch diverting from a main tube, channel, or cavity
Infundibulum = diverticulum of the brain floor
Rathke’s Pouch = diverticulum of the stomodeal roof/embryonic mouth)
near third ventricle (where hypothalamus is located)
peak is developed
eventually rathke’s pouch loses contact (regressing stalk)
Developing sphenoid bone (part of the cranium)
Mature structures:
posterior lobe and anterior lobe of pituitary, sella turnica = cavity, developing sphenoid bone around pituitary , all over roof of pharynx
Posterior pituitary (neurohypophysis)
neural tissue, derived from infundibulum (back of brain)
Anterior pituitary adenohypophysis
glandular tissue, derived from rathke’s pouch (front of brain
Primordial Germ Cells (PGCs)
Migrate from:
Yok sac (portion of placenta, only around for first 15% of gestation)——midgut—-mesentary—-gondal ridge
-ameboid movement
-chemotactic signal (movement towards the signal)
-when arriving at gonadal ridge:
stimulate proliferation of connective tissue
form primitive sex cords
cause gonadal ridge to enlarge and push against kidneys (testes forming near kidneys before dropping)
undergo mitosis to increase in numbers
(GONADAL SEX IS NOT DETERMINED YET)
Pronephros
Nonfunctional remnant of kidney formation in lower animals
Mesonephros
Functional bilateral pair of intermediate kidneys
produce urine, drains by mesonephric pair of ducts (1st 15% of gestation)
Metanephros
FINAL Adult form
Develop functional nephrons
1st 30-35% of gestation
Sexually indifferent stage
Mesonephric wolffian ducts in male
paramesonephric mullerian ducts in female
Key of Sex Determination for Males
Y chromosome or SRY gene (leads to testis formation)
-Sertoli cells (in testis) secrete anti-millerian hormone——related to paramesonephric duct, will degenerate it(AMH) and dihydrotestosterone (DHT= stronger testosterone, inhibit female reproductive system)
^govern spermatogenesis
AMH + testosterone degenerate paramesonephric duct
Desert Hedgehog (DHH) gene (transcription factor) differentation of fetal leydig cells = testosterone and dihydrotestosterone= male duct system
DHT = development of penis, scrotum, and accessory sex glands
Female Sex Determination
No SRY
Ovaries develop
NO AMH
Paramesonephric ducts = oviducts, uterus, cervix, and part of vagina
Will eventually form female tract
Male Development of Reproductive Tract (stage 1)
No interconnected tubes
Paramesonephric duct
Mesonephric tubules = future efferent ducts, from mesonephric duct
Rete tubules form close to mesonephric tubules
Undifferentiatied sex cords will be gonad (testis)
tunica albuginea around sex cords
Male tract development (Stage 2)
Epithelial cords shape from sex cords, future seminerferous tubules
Rete testis now connected to mesonephric tubules and epithelial cords
Mesonephric duct is forming off of rete tubules
Paramesonephric still present
Male tract development stage 3
100s seminiferous tubules formed
rete tubules formed complex interconnections
Mesonephric tubules = efferent ducts (6-12)
mesonephric duct = ductus deferens, also forms epididymis
Remembering primitive versus mature
Testicular descent
Gubernaculum= connective tissue
organ (ligament) that attaches to the ventral pole of the testis and extends to inguinal region of developing fetus
What controls gubernaculum growth? Decendin = insul3
Gubernaculum
grows after fusion of perioteneum and gubernaculum
enters in inguinal canal in viceral vaginal tunic, vaginal cavity, parietal vaginal tunic, pulling visceral growth
FINAL DESCENT = regression of the gubernaculum
^testis continues to move downwards
regresses until it forms a little knot at the bottom to anchors testis to bottom
(stallions anchoring hasn’t happened until after birth)
Final: vaginal cavity, visceral vaginal tunic, testes can still move for thermoregulation (closer or further away from body cavity)
What triggers growth of gubernaculum
gubernacular cells need MW testicular extract for significant growth (molecular weight proteins)
cryotiorchidism
bilateral sterile animal
inguinal hernia example below:
invasion of other organs from improper closure of peritoneum and inguinal ring, now intestines can drop down into female cavity
female development (stage 1)
paramesonephric duct development
First stage
future infundibulum
regressing tubules (not making connections)
epithelial cords
coelomic epithelium (future cortex)
paramesonephric duct/mullerian duct
Mesonephric duct still currently exists
female development stage 2
-regressing mesonephric
-regressing epithelial cords
-future ovarian cortex
-paramesonephric duct
-regressing mesonephric
-future infundibulum
female development 3 (first 40% of gestation)
regressing mesonephric, regressing epithelial, paramesonephric = future uterus + oviduct, regressing mesonephric, future infundibulum, primative follicles (no penetration, within cortex)
^Cells in clusters = cell syncitium
Cell synsitium
connections between germ cells/follicles, extracellular connections for similar developmental rates, look like o=chem chair/triangular structure
Stage 4 femal edevelopment
primordial follicles present! Remanants of mesonephric, ovarian medulla + cortex formed
Still paramesonephric for future oviduct/uterus, and future infundibulum
Regressing mesonephric duct
(in mare, there is still the inverted ovary that is forming)
total female development 1
cranial urogenital sinus = future bladder
fused paramesonephric ducts = cervix + uterine body (simplex, duplex, etc. formation = amount of fusion)
bud from urogenital sinus
caudal urogenital sinus = future vestibule
total female development 2
fused paramesonephric = cervix + uterine body
still have bud from urogenital sinus
total female development 3
uterine horn, uterine body, cervix, future bladder, cranial vagina, future urethra, vestibule, rectum
uterine horn, cervix, cranial = from paramesonephric, from mesoderm
Bladder + vestibule = ectoderm
cross section of female embryo 1
neural tube, notochord, aorta, regressing mesonephric, paramesonephric (oviduct future) gonad, gut
Gonads moving ventrally in wing like motion
ovary and paramesonephric still have distance from each other
(more anterior view)
cross section of female 2, more posterior
genital fold, regressing mesonephric duct, paramesonephric duct (future oviduct) more migration closer together
Gonads present
cross section of female embryo 3, even more posterior
remanant of mesonephric= gartners ducts
geneital fold = future broad ligament, connective tissue
periotenum = fused together (specifically talking about mesometrium of broad ligament)
Paramesonephric duct (future uterus)
chromosomal sex (heterogametic)
Mammals = Male = XY, Female = XX
Birds/Reptiles = Male = ZZ Female = ZW
Some lizards/tortoises have NO heteromorphic pair (determined by temperature and steroids)
in Mammals = one x is inactivated = barr body in somatic cells
XXY Klinefelter’s syndrome -= sterile, testicular hypoplasia
XO= turner’s syndrome = sterile, inactive ovaries
Hermaphrodites
Cogenital malformation in sexual development
True hermaphrodite
male psuedohermaphrodite
female psuedohermaphrodite
true in swine = ovatestis with epididymis on the end of uterine horn
Female pseudohermaphrodite (freemartin)
heifer born twin to a bull
-membranes of placental units fuse to occupy same cotyledon (interact with caruncles)
-common blood supply for male and female fetus
-AMH from male inhibits development of repro tract in female fetus
(male tract happens a little bit before female in development)
-ovaries cease growing = decrease in germ cells + NO ESTROGEN
-Infantile repro tract remains
-Produce testosterone and androstenedione (have male characteristics)
Gene defect in men
5 alpha reductase deficiency (dominican republic)
testosterone (enzyme 5 alpha reductase) 5 alpha dihydrotestosterone
XY men have external female genitalia and internal testis (as children), testes will eventually drops
can also be caused by a lack of androgen receptor
Testicular feminization
Gene defect in Women
Congenital Adrenal Hyperplasia
ACTH stimulates adrenal to produce cortisol but lack of enzyme for conversion of progesterone to cortisol increases high concentrations of testosterone causing masculinization
Exceptions to the rules
Three mammals where sex differentiation is unconventional and appears to be different from other mammals
-Spotted Hyenas
-Elephants
-Tammar Wallabies
Spotted Hyenas
reproductive tract is external (clitoris of the female looks more like glans penis), no external vagina
Elephant
layout of female repro tract, and orientation of male tract
female orientation looks more like male orientation
Tamir Wallabees
5 days before birth (day 22) STILL INDIFFERENT gonadal ridge
Day 9 postpartuition can see sex differentiation between scrotum and mammary gland pouch
-both have genital tubercle
(as a marsupial)