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Reproductive System (The Mammary Gland :glass_of_milk: (Colostrum (Lipids…
Reproductive System
Control Of Ovulation And The Corpus Luteum
Ovulation
Ovulatory Follicles Are Selected At The Onset Of Luteolysis (Large Domestic Animals)
Ovarian cycle is regression of follicle and growth of the next follicle.
Follicle that develop at CL regression time is the ovulatory follicle.
Final antral follicle development got 2 phases;-slow phase and accelerated growth phase.
Final growth phase initiated by luteal phase, slow pulse of gonadotropin secretion.
Faster pulse gonadotropin secretion promotes rapid follicle growth.
CL regress,↑ pulsatile gonadotropin secretion.
Follicles produce
Inhibin
to maintain dominant status.
Inhibin
inhibits
FSH
secretion.
Once the rapid growth phase is achieved, it must be exposed to gonadotropin immediately. If not, atresia( regression) of follicle happen.
Follicles that regress are invaded by inflammatory cells, filled by connective tissue, the follicles is replaced by Ovarian scar.
Ovulation Is Caused By An Estrogen-Induced Preovulatory Surge Of Gonadotropins
Preovulatory LH surge keep the granulosa and oocyte under control , by producing inhibitory substances such as "oocyte- inhibiting factor"and " Luteinizing-inhibiting factor".
"oocyte-inhibiting factor"= prevent oocyte from resuming meiosis.
" Luteinizing-inhibiting factor"= prevent granulosa from prematurely being changed into luteal tissue.
Resumption of meiosis 1 is important to form 1st polar body.
LH effect on granulosa to initiate luteinization( transfrom estrogen secreting cells to progesterone secreting cells).
Luteinization will decrease [ estrogen] and increase [progesterone].
LH surge also cause granulosa to produce
relaxin
and
prostagladin F2α (PGF2α)
,which affect the continuity of connective tissue of thecal layers in follicles to form a vessicle.
The vessicle contain hydrolytic enzyme to breakdown collagen matrix of the connective tissue.
Rupture of follicle is caused by the disintegration of connective tissue.
Estrogen signal the hypothalamus and adenohypophysis about the readiness of the follicles for ovulation.
Corpus Luteum(CL)
The Corpus Luteum Secretes Progesterone, Which Is Essential For Pregnancy
CL secrete progesterone to prepare the uterus for pregnancy.
Membrane propria hemorrhage from the vessels in the theca into the ruptured cavity.
The vascular system at the theca support cell growth and differentiation.
granulosa (dominant component) + theca cells = CL
In dog, small concentration preovulatory LH surge → expression of sexual receptivity.
Luteinizing Hormone Is Important For The Maintenance Of The Corpus Luteum
LH is luteotropin → maintain CL by ↓pulsatile LH release.
In rodent, prolactin is luteotropin ( release by copulation).
Prolactin also luteotropin for sheep and dog.
Nomal folliculogenesis → postovulatory CL development.
Regression Of The Corpus Luteum In Non-Pregnant Large Domestic Animals Is Controlled By Uterine Secretion Of Prostagladin F2α
CL regress to prepare the non-pregnant animals back to fertile state ASAP.
Luteal phase is about 14 days ( non- pregnant) .
Removal of uterus cause prolongation of luteal phase.
Uterus can control the life span of CL by secreting PGF2α.
PGF2α can cause CL to regress.
PGF2α and PGE cause luteoluysis in bitch and queen for pyometra ( uterine infection) treatment ad also use to induce abortion.
Mode of PGF2α transfer:-(1) local countercurrent transfer and (2) general systemic transfer
(1) Countercurrent transfer → movement of molecule from high concentration in the venous effluent (utero-ovarian vein) to an area of lower concentration ( ovarian artery).
(2) Systemic transfer → passage of molecules through through general circulatory system.
In sow and mare, PGF2α from one uterine hon can cause CL regress in both side ovaries.
PGF2α must be in pulsatile , 6 hours for 1 pulse, to complete luteolysis.
If not pulsatile, CL can recover and continue to function.
Uterus must exposed to estrogen and progesterone to synthesis PGF2α.
Estrogen initiate PGF2α synthesis.
PGF2α reduce progesterone production and release " luteal oxytocin".
"Luteal oxytocin" interact with the receptors in uterus to initiate another round of PGF2α synthesis.
Bitch experiencing infertility after too frequent estrous cycle.
Changes In Luteal Life Span In Large Domestic Animals Occur Because Of Changes In Prostagladin F2α Synthesis By The Uterus
Presence of embryo block PGF2α synthesis, to continue luteal phase.
Mares have prolonged luteal phase because inadequate synthesis of PGF2α.
Absence of uterine horn lengthen the luteal phase in ipsilateral horn animals.
In non-pregnant animals, inflammatory response to bacteria contamination in the uterus→ premature luteolysis → shorthening estrous cycle.
Short estrous cycle mostly related to uterine infection.
Ovarian Cycle
In Spontaneously Ovulating Animals, Ovarian Cycles have 2 Phases; Follicular and Luteal; Animals That Require Copulation Can Have Only A Follicular Phase
Ovarian cycle in non-pregnant animal, is defined as the interval between two successive ovulations.
ovulation seperating the follicular phase and the luteal phase.
"Spontaneous ovulators" are domestic animals that ovulatory process is governed by internal mechanism, which estrogen initiate gonadotropin release.
Higher primates, have clear seperation between two phases.( no overlap)
Cow have large antral follicle present during luteolysis. Mare have follicle growth that can ovulate during luteal phase.
In large domestic animals, follicle growth is telescoped into luteal phase.→shorter cycle.
" Induced ovulator" → animals that need copulation for ovulation to occur. Examples; cats, rabbits, ferrets, mink, camel, llamas, alpacas.
Copulation act as estrogen → stimulates ovulatory release of gonadotropins.
Induced ovulators need high [estrogen] before can respond to copulation.Without copulation, follicle cannot last long and regress rapidly.
Follicle waves can some overlap in llamas & alpacas,distinctly overlap in cat, closely overlap in rabbit.
The Luteal Phase Is Modified By Copulation In Some Species
In rodent, luteal phase can be extended by copulation.
Copulation initiate prolactin release → prolonged luteal activity (10-11 days).→ cause
''pseudopregnancy"
In canine, spontaneous regression of CL marking diestrous end →[ prolactin ]↑. the bitch will lactate, nest, nurture object due to the false pregnancy.
Clinical Correlations
Inability To Impregnate A Mare
1.Clinical examination
Mare has breed for 2 times, still not pregnant, artificially inseminated with good semen. The mare had no fluid in uterus and good body condition, her cervix will relaxed and edema will maximize.On palpation, large CL present indicates she is in diestrus. The mare if given PGF2α to get her back in heat.PGF2α will cause CL to regress and she supposely will be in heat in 5-7 days.
Treatment
The mare is rechecked 4 days after PGF2α administration to monitor the growth of follicles and the tone of the cervix as well as the number of edema..The mare is given hCG to stimulate FSH and LH to help induce ovulation. The mare is rechecked after 14 days and found to be pregnant.
Persistent Luteal Phase In The Mare
Clinical Examination
A mare foaled before and was not bred during the foal "heat" because of retained placenta. The mare do not return to estrus after 40 days, The cervix is tight and small nd considerably tone. The uterus also tone. The ovaries are in normal size. The mare is not attracted by stallion.Suspected persistent CL because the tone cervix and uterus suggest that the genital tubular system is influenced by progesterone.
Treatment
Administration of PGF2α to initiate regression of persistent CL. The regression of CL allows the current dominant follicle to continue develop and produce estrogen→ bring the mare to estrus.
Reproductive Cycles :recycle:
Reproductive Cycles
The 2 Types Of Reproductive Cycles Are Estrous And Menstrual.
Estrous and menstrual cycle ( ovarian cycle representing the interval between 2 successive ovulation).
Estrus = period of sexual receptivity( on heat)
Estrous cycle refer to domestic animals, menstrual refer to primates- menstruation( vaginal discharge of blood).
End of the luteal phase is the 1st day of estrous cycle.
Proestrus = period of follicle development, after CL regress .
Metestrus = period of initial development of CL.
Diestrus = period of mature phase of the CL.
In dogs and cats, sexual receptivity is measured from serum progesterone level.
CL represent the culmination of follicle growth and ovulation.
Puberty And Reproductive Senescene
Puberty Is The Time At Which Animals First Release Mature Germ Cells.
Puberty is the onset of reproductive life.
In primates, 1st menstrual bleeding is the onset of puberty.
Time of 1st ovulation.
Onset of puberty = ↑[GnRH] synthesis from hypothalamus → [gonadotropin]↑ → follicle growth.
Hypothalamus is highly sensitive to -ve feedback inhibition by estrogen.
Puberty is the maturation of hypothalamus,→ decreased sensitivity to the -ve feedback inhibition.→ relase GnRH.
Photperiod is the exposure to the light.
Photoperiod allows sensitivity of hypothalamus to ↓ response to -ve feedback by estrogen →puberty onset.
Photoperiod → secretion of gonadotropin↑, follivle growth ↑.
Gonadotropin surge → promote luteinization with short life span.
Initial luteal structure die → another gonadotropin surge → ovulation → CL with normal life span, initiate ovarian activity.
Photoperiod can have suppresive effect on puberty timing in animals with light controlled ovarian activity ( cats).
Long photoperiod → male lamb lose sensitivity to estrogen feedback inhibition → promote spermatogenesis.
Reproductive Senescene In Primates Occurs Because Of Ovarian Inadequacy,Not Inadequacy Of Gonadotropin Secretion.
End of ovarian activity→ menopause.
Ovarian failure → essence → depletion of oocytes → menopause.
1st factor = follicle fails to develop from their primordial state, ↓ no. of follicles.
2nd factor = absence of gonadotropin receptors prohibits follicles entering the gonadotropin-dependent stage of growth.
Menopause initiated by irregular ovarian cycle, failure of follicle development and ovulation.
Gonadotropin secretion↑,[estrogen] ↓, ↓-ve feedback inhibition.
Reproductive senescence not recognized in domestic animals, because they are slaughtered before that happens.
Dog experience reproductive senescene, neonatal mortality ↑, as age ↑.
Sexual Behaviour
Sexual Receptivity Is Keyed By The Hormones Estrogen and Gonadotropin- Releasing Hormone In The Female And Testosterone In The Male.
Sexual behavior depends on exposure/ no exposure of hypothalamus to testosterone during neonatal period.
Testosterone cause masculiniation of sexual centers in the hypothalamus ( medial preoptic area).
1st principle, magnitude of [hormone] affect sexual behavior is small. ( cat)
2nd principle, synergism betwen hormones is imporyant for sexual receptiveness. (dog = estrogen priming followed by progesterone )
3rd principle, sequence of exposing to hormone is important .(ewe, progesterone priming b4 estrogen exposure → manifest estrus)
Estrogen required for sexual receptivity.
Progesterone important to sheep. Sheep must expose to progesterone, then only can respond to estrogen.
Dog = prior exposure to estrogen makes the female attractive to male,but does not produce sexual receptivity, so require exposure of progesterone for estrus.
In other domestic animals, progesterone is inhibitory for estrous activity.
Testoterone important for libido ( sexual desire) in female primate.
Degenerating follicles theca secrete androgens androstenedione and testosterone.
Androgens maintain libido in males.
Castrated animal can still have libido as they have androgen ( which is adrenal origin).
GnRH also important to sexual receptivity.(cause estrus).
↑[GnRH] synthesis, ↑ gonadotropin, ↑ preovulatory gonadotropin surge, → ovulation.
External Factors Controlling Reproductive Cycles
Photoperiod, Lactation,Nutrition,And Animal Interaction Are Important Factors That Affect Reproduction.
Photoperiod
Animals have continuous ( cylical ) ovarian activity, as well as period of no ovarian activity ( anestrus).
Cats and dogs are positively affected by ↑ photoperiod.
Goats and sheep are positively affected by ↓ photoperiod.
Negative respond to photoperiod = suppress ovarian activity .
Main translator of photoperiod is the pineal gland → produce melatonin in response to darkness.
Melatonin have +ve effect on reproductive cycles.
Sheep =↑ darkness exposure, ↑ melatonin,→ maintain ovarian activity.
Systemic implant of melatonin to sheep in spring → ↑ovarian activity, ↑no.of multiple ovulation of breeding season.
Cat is most sensitive to photoperiod change → estrus → mature antral follicles.
Suppressive effect of photoperiod can be overcomed by exposure to artificial lightning regimens.
Lactation
Lactation suppress ovarian activity.
Complete suppression in sow, do not come into estrus until piglet are weaned.
Dairy cow are not suppressed by lactation unless nutrition inadequacy.
Photoperiod can overcome lactation suppression on ovarian activity in goat and sheep.
Mare have no lactation suppresive effect on ovarian activity.
Suckling can stimulate prolactin synthesis, ↑ lactation.
Inhibiting factors ( dopamine and GAP) are suppressed by suckling.
Pheromones
Pheromones allow communication among animals through olfactory synthesis.
Sex pheromone affect sexual behavior.
Pheromone found in sebacous gland, reproductive tract and urinary tract.
“ Whitten effect”= introduce male odor to induce estrus in female, stimulates the synthesis and release of gonaotropins.
“ Bruce effect”= introduce strange male to recently bred female to block pregnancy. The strange male odor blocks the release of prolactin , CL regress → miscarriage.
Pheromones help male attracted to female at sexual receptivity period.
Methyl-p-hydroxybenzoate, isolated from vagina secretion of dog in proestrus and estrus → produce intense anogenital interest to male.
Sow assume a breeding (rigidity) stance when exposed to male’s urine.
Androgen can act as pheromones.
Male marks their territory with urine ( musk-type odor).
Human pheromone is perfume , civetone derived from civet cat.
“Whiten effect” can manipulate estrous cycle of animal.
Interaction of rams with ewes over extended [eriods of anestrus → earlier ovarian activity.
“Physical contact” → sight can influence gonadotropin secretion.
“Whitten effect” → use to influence pig puberty onset.
“Dormitory effect”→ synchronization of menstrual cycles in roommate women and bitches in kennel.
Inadequate Nutrition Results In Ovarian Inactivity, Especially In Cattle.
Dairy cow require enough feed to maintain body weight, growth and lactation.
Animals need enough nutrition to initiate ovarian activity.
Negative nutritional balance will suppress and delay ovarian activity.
Clinical Correlation
Sexual Attractiveness In Spayed Bitch.
Clinical examination
Dog is attracting male despite already undergone ovariohysterectomy.The bitch does not allow intromission. The vulva is slightly swollen with small discharge present. Vaginal smear reveals increased number of neutrophils. Suspected urogenital tract infection. Reproductive endocrine panel and urinalysis obtained show low [estrogen]and low [progesterone].Male dogs are attracted by the odors generated by urinary tract infection. The bitch does not allow intromission due to low progesterone level.
Treatment
Bladder infection is treated, keep the bitch away from other male until infection has cleared.
The Mammary Gland :glass_of_milk:
Anatomical Aspect Of The Mammary Gland
The Milk-Secreting Cells Of The Mammary Gland Develop Through Proliferation Of Epithelium Into Hollow Structures Called Alveoli
Embryonic ectoderm form the mammary ridge, and the develop to form mammary bud.
Milk secreting cells from the primary mammary cord epithelial cells, form the hollow circular structures-" alveoli"( functioning unit parenchyma).
Nipple connect internal milk-secreting system to external surface.
Male nipple do not have developing mammary cord to form glandular tissue.
Most Of The Milk That Accumulates Before Suckling Or Milking Is Stored In The Alveoli, Even Though Animals Have Enlarged Milk- Storage Areas Called Cisterns.
Duct system connect the alveoli to nipple to pass milk.
Cattle,goat, sheep have 1 final duct per gland.
Mare and sow have 2 main ducts per gland.
Cow and Doe(goat) have cisterns- specialised area for holding milk.
Mammary gland develop in pairs.
Goat, horse, sheep- 1 pair mammary gland
Cattle - 2 pairs mammary gland.
Sow and Bitch= 7-9 pairs mammary gland.
Cattle, goat , horse, sheeps = mammary gland are closely apposed to each other to form "udder".
A Suspensory System Involving The Udder Of The Cow Allows The Animal To Carry A Large Amount Of Milk.
Median suspensory ligament (between mammary glands), composed of elastic connective tissue.
Suspensory system hold the udder to store heavy weight of milk.
Lateral suspensory ligament ( non elastic), originates from prepubic and subpubic ligament.
Milk Removal
Efficient Milk Removal Requires The Release Of Oxytocin, Which Causes Contraction Of Muscle Cells That Surround The Alveoli (Myoepithelial Cells), And Movement Of Milk Into The Ducts And Cisterns.
Myoepithelial cell respond to oxytocin and contract to force the milk out.
Suckling stimulation release oxytocin from neurohypophysis.
Auditory, visual , olfactory sensory stimuli for oxytocin release too.
Oxytocin release through Ferguso reflex.
Ferguso reflex = cervix stimulation by blowing air into the vagina to induce oxytocin release.
Oxytocin initiate passive part of lactogenesis → release prolactin.
Control Of Mammogenesis
Initial Development Of The Mammary Gland Is Programmed By Embryonic Mesenchyme
Development of mammary gland control by genetic and endocrine system.
Fetal administer exogenous hormone to mother - activate mammary gland secretion.
Proliferation Of The Mammary Duct System Begins At Puberty, With Ducts Under The Control Of Estrogens, GH, Adrenal Steriods, And Alveoli Under The Control Of Progesterone And Prolactin.
Mammary gland develop at puberty but inactive until pregnancy happen.
Estrogen, GH, adrenal steriods = proliferations of duct system.
Progesterone ,prolactin = proliferation of alveoli
Udder develop in middle gestation and begin to secrete milk at the latter gestation, (↑[prolactin])= form colostrum.
Many alveoli → lobules → lobes
Colostrum
Prepartum Milk Secretion ( Without Removal) Results In The Formation Of Colostrum.
Milk formed before parturition - "colostrum".
Colostrum represent lactogenesis activity.
Progesterone & estrogen ( prolactin inhibitor) being removed before parturition.
The Ingestion Of Colostrum Is Important Because Of The Passive Immunity It Confers Through The Presence Of High Concentrations Of Immunoglobulins.
Provide nutrient, temporary passive immunity to the youngs.
Contain IgA produced by B-lymphocyte plasma cell when mother exposed to microorangisms.
neonate receive immunity against pathogens experienced by mother.
The Time Immunoglobulins Can Be Absorbed Through The Neonatal Gut Is Limited To The First 24 to 36 Hours of Life.
Neonates have limited time ( 24-36 hours) to absorb immunoglobulin protein from colostrum.
Colostrum contain antimicrobial factors ( lysozyme, lactoferrin lactoperoxidase).
Lipids (Particularly Vitamin A) And Proteins (Caseins And Albumin) Are High In Concentration In Colostrum, Carbohydrate (Lactose) Are Low.
High in Vitamin A.
Placental transfer of Vitamin A is low for calves, piglets at birth, but can be compensate by colostrum ingestion.
Casein and albumin high in colostrum.
[lactose]↓, inhibited by progesterone.
Lactogenesis
Prolactin, Inhibited By Dopamine And Stimulated By Vasoactive Intestinal Peptide(VIP), Is The Most Important Hormone Involved In The Process Of Milk Synthesis, Or Lactogenesis, GH Is Also Important For Lactogenesis
Prolactin promotes milk secretion ( lactogenesis).
Prolactin can be released by suckling stimulus.
Sensory stimuli send impulse to hypothalamus to synthesis dopamine is blocked, in contrast, paraventricular nucleus produve VIP ( prolactin stimulator).
GH also promote lactogenesis.
The Release Of Fat Into Milk From The Alveolar Cell Involves Constriction Of The Plasma Membrane Around The Fat Droplet; Fats Are Dispersed In Milk In Droplet Form.
Alveolar cells synthesize fats, protein sad carbohydrates→extrudes into alveolar lumen.
Fat droplets accumulates at basal cytoplasm, then move to apex → form droplets.
Fat droplets ( contain a portion of cytoplasm ) disperse in milk.
Milk Proteins And Lactose Are Released From Alveolar Cells By The Process Of Exocytosis.
Milk protein ( casein) synthesized on endoplasmic reticulum and phosphorylated and packed by Golgi apparatus.
Lactose also synthesized the same way.
Milk protein and lactose transported out by exocytosis.
Composition Of Milk
Fats Are The Most Important Energy Source In Milk.
Milk fats = monoglycerides, diglycerides, triglycerides, free fatty acids, phospholipids and steriods.
Triglycerides is the main component.
Marine mammals milk has high fat content to insulate heat loss of the young.
Domestic animal less milk fat.
Lactose,Composed Of Glucose And Galactose, Is The Main Carbohydrate Of Mammalian Milk.
Lactose is the main carbohydrate.
Glucose + galactose = lactose
α-lactalbumin + galactosyl trnasferase = Lactose synthetase
Lactose synthesis is suspended by progesterone ( inhibit α-lactalbumin fomation ) until parturition.
Prolactin is lactose synthetase stimulator.
Animal need lactase in jejunum to digest lactose, some adult do not have lactase - cause diarrhea.
The Main Proteins In Milk Are Called Caseins And Are Found In Curd.
Main milk protein is caseins.
Casein can be removed as curd from milk through " curdling or coagulation ".
When albumins and globulins remain in milk = "whey".
First Nursing
Carbohydrate Stores Are Good In Neonates Born As Singles Or Twins,Whereas Carbohydrate Stores Are Low In Neonates Born In Litter; Consequently The Former Can Stand A Longer Interval To First Suckling Than Can The Latter.
Cattle, horse, sheep, goat neonates have to stand suckle and locate the mammary gland, thus the neonate require enough carbohydrates supply to do so. ( nurse in 2 hour interval).
Cat, dog, pigs - the young immediately nestled toward mammary gland and suckling in less than 30 minutes after birth. (nurse in 1 hour interval).
If suckling delay, neonates suffer from hypoglycemia, which lead to bowel stasis and neonatal sepsis.
Rabbit nurse their young 24 hour intervals.
Diseases Associated With The Mammary Gland
The Main Disease That Affect The Mammary Gland Directly Are Mastitis ( Prevalent In Dairy Cattle And Dogs) And Neoplasia ( Prevalent In Intact Dogs And Cats)
Mastitis = inflammation of gland.
mastitis caused by injury to teat canal from repeated strecthing during milking, easily exposed to microorganism , lead to infection.
Connective Tissue form in udder, swollen, limits the duct and alveoli to proliferate, decrease milk production.
Mastitis treatment = antiinflammatory and antibacterial agent.
Neoplasia = mammary tumour when mammae exposed to estrogen and progesterone.
Neoplasia treatment = ovariectomy before puberty to reduce risk.
The Main Conditions That Involve The Mammary Gland Indirectly Are passive Transfer Of colostrum (Mare) And Hypocalcemia Caused By The Transient Drain Of Calcium That Occurs With Initiation Of Lactation ( Dairy Cattle) Or During The Prenatal Period (Dog).
Immunological disease, transfer of RBC agglutinating antibody to the fetus through milk.
Fetal RBC pass into maternal system , and form antibody against fetal RBCs ( foreign to mother ).
RBC agglutinating antibody concentrate in colostrum.
Foals undergo hemolytic crisis and can die if not treated.
treatment = muzzle the foal for the 48 hours after birth, feed on frozen colostrum.
same as neonatal isoerythrolysis in kitten.
Hypocalcemia = lack of calcium due draining of maternal Ca2+ to form milk.Animal tend to become weak and unable to stand.
Ca2+ administer can recover in 10-20 minutes.
Lactation Cycle
Milk Production Peaks At 1 Month Postpartum In Dairy Cattle, Followed By A Slow Decline In Production; Milking Usually Stops At 305 Days Of Lactation So That The Animal Can Prepare The Mammary Gland For The Next Lactation.
Cow " dried up" after 305 days lactation period.
Lactation cycle is change colostrum to normal milk.
Dairy cow is forced to stop lactating to prepare for next lactation.
Back pressure of milk in alveoli gradually inhibit milk secretion by alveolar epithelial cells.
Alveolar cell regress, small duct regress = "involution".
Involution happen to replace the regressed alveoli and duct.
Lactation Can Be Induced By Hormone Administration ( Estrogen And Progesterone ) And Enhanced By GH And Increased Photoperiod Exposure.
" Induction of lactation" apply to those animals with high-lactation record but poor reproductive performance.
Estrogen + Progesterone = induce alveolar development to produce milk.
GH enhance lactation by absorb and direct nutrient to milk synthesis system.
Negative energy balance, GH mobilize body fat to form milk.
Positive energy balance, GH show no effect on body fat metabolism.
GH decrease energy balance in cow, can be compensate by increase feed consumption.
Thyroid hormone use to increase lactation in cow.
Dog, gynecomastia ( enlarged mammary) is profound hypothyroidism→ TRH increase → prolactin increase.
Long photoperiod increase cow lactation by increase prolactin synthesis.
Low dose of oxytocin and metaclopramide ( dopamine D-2 receptor antagonist) → improve bitch lactation.
Queens sensitive to photoperiod (expose to dark), melatonin ↑, prolactin ↑.
Clinical Correlations
Pregnant Mare That Does Not Have Sufficient Milk Or Udder Development.
Clinical examination
A mare is pregnant, and current under vaccination and deworming, the mare is in good body condition and the foal is viable. The mare was fed with hay and fescue. Fescue contain endophytic fungus,
Neotyphodium coemophialum
, produce alkaloid toxins that are dopaminergic and inhibit prolactin. The mare has limited udder development.
Treatment
Domperidone administration to inhibit the dopaminergic effects.If domperidone is started 5 to 10 days before parturition to allow enough time for the mare to develop sufficient milk.
Neonatal Isoerythrolysis
Clinical Examination
A mare that have foaled 3 times. The mare is normal and in good body condition. The last 2 foal died within 2-4 days after birth. The mare had colostrum and milk. Suspect neonatal isoerythrolysis as the foals are healthy right after birth, and weakened after consuming colostrum. The mare exposed to RBCs of fetus during pregnancy or the stallion RBCs. The RBCs are foreign to the mare, and develop antibody against the fetus RBCs if the the foal inherited same blood type as the father. The antibodies cannot pass through placenta but concentrated in colostrum. Once the foal suckle the colostrum,it acquire the antibodies that will react to its own RBCs. The foal develops type II hypersensitivity reaction.
Treatment
Muzzle the foal after birth and feed the foal with frozen colostrum from other mare for the first 1-2 days to prevent absorption of the antibodies from the mother. If the foal already consumed the colostrum from mother, immediate blood transfussion are required for the foal survival.
Reproductive Physiology Of The Male
Functional Anatomy
The Male Reproductive system Consists Of Many Individual Organs Acting In Concert To Produce Spermatozoa And Deliver Them To The Female's Reproductive Tract.
Scrotum made from subcutaneous fibroelastic and muscular layer called “tunica dartos”.
Testicular artery arranged in “ pampiniform plexus” → conutercurrent heat exchange for thermoregulations.
Horse testes have many sweat and subaceous gland for thermoregulation purpose.
Testis carry out steroidogenesis→ androgen production( Leydig cell) and generation of haploid germ cells by spermatogenesis ( seminiferous tubules).
3 compartment of testes ;-(1) Interstitial tissue compartment [ Leydig cells bath in testeosterone rich fluid];-(2) Basal compartment [ sperm undergo mitosis];-(3) Adluminal compartment [ spem undergo meiosis].
Sertoli cells nourish germ cells, extending from basal to adluminal compartment.
Sertoli tight-junction complex → blood-testeis barrier.(prevent compound from the blood and interstitial fluid enter the adluminal compartment).
Spermatogenesis require lower temperature than the core body temperature.
Failure of testes to descend from inguinal canal→ cryptorchidsm ( if bilateral- sterile).
Epididymis is where spermatozoa are concentrated, undergo maturition ,and acquire fertilizing capacity.
Sperm in caput(head of epididymis) are immotile and incapable of fertilization.
Sperm from caput to corpus are motile and capable of fertilization.
Mature sperm are stored from cauda to deferen duct.
Bull and stallion have prominent ampullae as extra sperm storage depot.
Dog have prominent prostate gland, but no bulbourethral and seminal vessicles.
Cat have prominent bulbourethral, but no seminal vessicles.
Llama have small bulbourethral and prostate gland,but lack seminal vessicles.
Penis = thick fibrous capsule ( tunica albuginea), Cavernous spaces ( Corpus Cavernosum), Corpus Spongiosum
Erection = ischiocavernosus muscle contract, corpus cavernosum and corpus spongiosum parasympathetically relax, cavernous space ↑, blood filled in→ penis elongated and turgid.
Scrotum, cremsater muscle and testicular artery and vein → thermoregulates the testes.
Genital organs are testes, scrotum,spermatic cord, external cremaster muscle,epididymis, deferent ducts, accessory glands, and penis.
Emission Is The Release Of Spermatozoa And Accessary Gland Fluids Into The Pelvic Urethra, Whereas Ejaculation Is The Forceful Expulsion Of Semen From The Urethra.
Emission caused by contraction of ductus deferens and accessory gland.
Ejaculation caused by rhythmic contraction of bulbouspongiosus, ischiocavernosus and urethralis muscles.
After ejaculation, cavernous space ↑, blood outflow ↑, contraction of penis muscle withdraw penis back to prepuce.
Spermatogenesis
Spermatogenesis Is A Lengthy Orchestrated Process In which Diploid Stem Cells Divide By Mitosis To Maintain Their Own Numbers And Cyclically Produce Progeny That Undergo Meiotic Division And Differentiation Into Haploid Germ Cells.
3 stage of spermatogenesis ;-(1) spermatocytogenesis,;-(2) meiosis;-(3) spermiogenesis.
Spermatocytogenesis- (a) type A spermatogonia meiotic division→maintain population of stem cells.(b) type A spermatogonia mitosis→type B spermatogonia→spermatocytes.
Spermiogenesis = formation of acrosome, flagellum and extensive shedding of cytoplasm, forming the head, middle piece and tail.
Head- contain acrosome hydrolytic enzyme to penetrate oocyte.
Middle piece- contain mitochondria provide energy.
Tail - flagellum movement.
Spermatogenesis take about 60-70 days.
Potential sperm production loss, degenerating during spermatogenesis.
3.Hypothalamus-Pituitary-Testicular Axis
The Reproductive System Of The Male Is Regulated By The Hypothalamus, Which Is Normally Linked To The Anterior Pituitary And Testes By LH And FSH.
Hypothalamus secrete GnRH in pulsatile → adenohypophysis→ secrete gonadotropin(FSH & LH).
FSH and LH have same α-subunit but different specific β-subunit.
Low-amplitude GnRH pulse→FSH release.
High- frequency GnRH pulse→LH release.
LH bind to Leydig cell membrane receptor→ convert cholesterol to testosterone.
Androgen diffuse into blood and lymph and bound to “androgen- binding protein”(ABP), produced by Sertoli cells.
[androgen]↑ promote spermatogenesis.
ABP accumulates testosterone and dihydrotestosterone in high concentration.
Testosterone target on peritubular myoid cells and Sertoli cells.
ABP facillitates androgen transport from testis to epididymis.
FSH target Sertoli cells receptors.
FSH and testosterone stimulate Sertoli cell to synthesize ABP, inhibin, activin, estrogen, transferrin.
Sertoli and Leydig cell interact in paracrine manner.
FSH direct Sertoli →inhibin →Leydig to produce steroids (steroidogenesis).
Inhibin stimulates steroidogenesis of Leydig.
Inhibin & testosterone = complex feedback regulation of pituitary function.
Gonadal steroid suppress FSH secretion.
Inhibin also suppress FSH release.
FSH and LH promote spermatogenesis.
4.Puberty
Puberty Is Not Synonymous With Sexual Maturity
Puberty = when male able to produce sufficient number of sperm to impregnate a female.
10% of sperm are motile.
Puberty Results From A Continuous Process Of Endocrine Changes That Are Initiated Shortly After Birth.
Target organ= pituitary gland, gonads , steroid-dependent tissue.
Hypothalamus initiate puberty.
Puberty happen when hypothalamus-pituitary complex become desensitized to feedback inhibition of gonadal steroids.
Desensitized→↑[GnRH] release, ↑ FSH and LH → initiate puberty.
Puberty factor -breed, energy intake , season of birth.
Prepubertal children secrete low concentration of FSH and LH, thus indicate normal functional hypothalamic- pituitary- gonadal axis.
Sex steroid lower down the low concentration of FSH and LH.
5.Anabolic Steriods
Anabolic Steriods are Androgen Derivatives That Exert Negative Feedback On The Hypothalamic- Pituitary-Testicular Axis
Anabolic steroid improve perfomance by ↑ mental attitude,↑ stamina, ↑ physical strength.
Anabolic steroid is androgen derivatives, function same to testosterone.
Anabolic steroid affect pituitary function and cause long lasting impairment of testicular endocrine function.
Small and soft testical.
“Stanozolol” and “boldenone undecyclenate” are 2 common horse anabolic steriod.
Anabolic steriod ↓ sperm concentration, motility, number of sperm per ejaculation.
Testicular degeneration= shrunken Leydig cell and spermatid phagocytosis.
Using ↑ dose of testosterone/ anabolic steroid= “hypogonadotropic hypogonadism”
Reduced fertility= sterile.
Clinical Correlations
Infertility In A Stallion
Clinical Examination
A stallion mated with 10 mares but only 1 mare is pregnant.The stallion is normal and not under any medication. The stallion was given steroids to improve performance.The stallion have normal libido and ejaculate 2 times in 1 hour. The semen samples show poor spermatozoa concentration,low sperm number, many abnormal spermatozoa and immature germ cells. The steroid given have same function as testosterone, which in high dosage, it will cause negative feedback effect to reduced spermatogenesis and may lead to permanent infertility. The stallion has small and soft testes.
Treatment
Other than time, there is no treatment to erase the negative feedback effect of anabolic steroid. Maybe after a certain period of time, when the steroid effect wear weaken or totally off, the stallion just can breed with small number or mares with artificial insemination. The stallion need to be reexamined in several month to see any improvement in sperm morphology.
Control Of Gonadal And Gamete Development
3. Hypothalamopituitary Control Of Reproduction
The Hypothalamus & Adenohypophysis Secrete Protein And Peptide Hormone, Which Control Gonadal Activity
Hypothalamus have many neurons, known as “ Nuclei”
“Nuclei” secrete peptide hormone
Peptide hormone move to pituitary by “Neuronl axon/ Vascular portal system”
Pituitary responds to hypothalamic peptide to produce hormones
The Adenohypophysis(Pars Distalis) Produce FSH,LH and Prolactin To Control Reproductive Processes
3 parts of pituitary
- Pars Distalis/Adenohypophysis
→ FSH + LH = (gonadotropin) →folliculogenesis & ovulation
→ Prolactin
→ GH
→ ACTH ( corticotropin)
→ TSH
- Pars Intermedia
-Pars Nervosa/ neurohypophysis
→neurophysins (vasopressin + oxytocin)
Pars Distalis derived from Rathke’s pouch endoectoderm.
Pars Intermedia & Pars Nervosa derived from neuroectoderm.
FSH = follicles growth, LH = follicles maturation (ovulation)
Neural stalk ( connect Hypothalamus to neurohypophysis) contain “Nuclei” axon
Hypothalamic neurons are "supraoptic"(→vasopressin) and "paraventricular"
(→ oxytocin)
Hypothalamus do not have axon in neural stalk connection with adenohypophysis
“ venous portal system’’ connect hypothalamus to adenohypophysis.
GnRH= Gonadotropin Releasing Hormone, ←produced by medial preoptic nucleus.
Dopamine & amino acid are produced in arcuate nucleus.
GnRH-Associated Peptide (GAP)→ synthesis GnRH, Oxytocin, Vasopressin.
GAP stimulate FSH & LH release, but inhibit prolactin secretion
1. Organization Of Gonads Is Under Genetic Control
Female
yolk sac germ cells migrate to genital ridge
genital ridge epithelium cells form the sex cord → follicle cells → granulosa cells (surround oocyte)
genital ridge mesenchymal cells form the theca cells
Müllerian duct form the oviduct
bursa→ direct channel for oocyte during ovulation
Male
yolk sac germ cells migrate to genital ridge
genital ridge epithelium cells form the sex cord → follicle cells → granulosa cells → Sertoli cells
genital ridge mesenchymal cells form the theca cells → Leydig cells
Wolffian duct (mdullary cord from mesonephros)→ Vas deferens, epididymis & urethra
germ cells pass through closed tubular system
4.Modification Of Gonadotropin Release
Pulsatile pattern
GnRH stimulated
GnRH downregulate gonadotropin secretion
GnRH interrupt GnRH receptor, block signal send to gonadotrophs
Gonadotropin secretion high in follicular phase, low in luteal phase.
Estrogen decrease pulse amplitude, ↓pA
Progesterone decrease pulse frequency, ↓pF
Follicular phase → low progesterone,(↑pF) and high estrogen (↓pA) = help in maturing follicle
Positive feedback, ↑ estrogen secretion by ↑ gonadotropin secretion
Gonadotropin surges in to lead ovulation.
Follicles respond to preovulatory gonadotropin surge →↓[estrogen]
gonadotropin modified to estrogen & progesterone →↓[ gonadotropin]→negative feedback
Hypothalamus secrete (1st) β-Endorphin (opioid peptide)→ inhibit LH secretion
(2nd ) Inhibin hormone, produced by granulosa cells,inhibit gonadotropinn & FSH secretion
[FSH]↓, control number of follicles bring to maturity
Male do not have positive feedback mechanism,because gametes are produced continuously in closed tubular system
(3rd) Prolactin, produced from adenohypophysis → lactation in mammal,mostly inhibitory secretion, away from hypothalamus→[prolactin]↑
Dopamine (from arcuate nucleus),GABA & GAP inhibit prolactin secretion
Dopamine agonists = Bromocriptive and Cabergoline are prolactin supressor, they are ergot-type compounds. Cabergoline promote luteolysis
Arcuate nucleus neurons = Tuberoinfundibular dopamine neuron (TIDA)
Hyperprolactinemia is over secretion of prolactin, caused by failure of “prolactin inhibiting factor” on the dopamine receptor, may also caused by reduction of TIDA neurons activity in hypothalamus.
“Prolactin releasing factor” is TRH ( thyrotropin-releasing hormone)
lactotropes have TRH receptors.
“vasoactive intestinal peptide”(VIP) stimulate prolactin secretion.
Estrogen ↑[prolactin],by ↓ lactotropes sensitivity to dopamine,↑ TRH receptors.
2. Sexual Organization Of The Genitalia And Brain Depends On The Presence/ Absence Of Testosterone
Female
tissue fold to form labia → vulva → clitoris
Wolffian duct regress →remnannt→ epoophoran, paroophoron, & Gatner’s cyst
Müllerian duct develop → oviduct, uterus, cervix & vagina
Gonad= ovary
If androgen is absent in exposure to hypothalamus→ female
Male
Rete testes produce Müllerian -Inhibiting Factors → Müllerian duct regress
Müllerin duct regress→ remnant →Appendix testes, Utriculus prostaticus
Wolffian duct remain and develop due the presence of androgens.
Müllerian duct is “permanent”
Wolffian duct is “ temporary” (remain only if response to male hormone)
5α-reductase help testosterone convert to dihydrotestosterone → masculinization of tissue
synthetic 5α-reductase inhibitors use for prostatic disease treatment
male labia tissue form scrotum, clitoris form penis
If hypothalamus is exposed to androgen before birth→male
5.Ovarian Follicle Development
Gamete Development Occurs Initially Without Gonadotropin Support and Subsequently With Pulsatile Gonadotropin Secretion
Oocyte proliferate by mitotic division ( at birth)
begin to use meiosis division after birth by the influence of “meiosis- initiating factor”( produced by rete ovarii)
Proliferation stuck at Meiosis 1 (Diploteme / dictyate stage) by “meiosis- inhibiting factor” (←produced by developing follicle cells)
Follicle cells produce an outer basement membrane( membrane propria)
Follicle cells divide to granulosa cells( many layers)→ secrete zona pellucida surrounds oocyte
Granulosa cells have many gap junction, no bolld supply at membrane propria.
Thecal layers surrounds membrane propria = preantral follicle
Initial follicle growth is controlled by genetic
In the Prenatal Follicle, Gonadotropin Receptor for LH Develop On The Theca, Which Results in Androgen Synthesis; FSH Directs The Granulosa to Transform the Androgens To Estrogens
Granulosa and theca have LH receptors
FSH and LH receptors develop on granulosa and theca respectively
Antral follicle = fluid appearance ( follicular fluid- secreted by granulosa) filled the antrum cavity
“cumulus oophorus”= stalk of granulosa to the follicular cells.
LH → Theca → produce testosterone & androsterone → diffuse membrane propria →granulosa → convert androgens to estrogen (estradiol-7)
Granulosa cannot form androgen, while Theca has limited capacity for producing estrogens → cooperative effort concept → “2 cell mechanism”
Estrogen = Positive feedback at granulosa → stimulate mitotic division, ↑ follicular size
FSH receptors → antral follicle sensitive to FSH and grow with FSH secretion.
3.Late In The Ovarian Phase, LH Receptor Develop On The Granulosa, hich Permits the Preovulatory Surge Of Luteinizing Hormone To Cause Ovulation
FSH & estrogen initiate LH receptors formed on granulosa
FSH receptor disminish
High [estrogen] ,initiate preovulatory surge of gonadotropin
LH leads to ouvulation
5.Clinical Correlations
Androgen Insensitivity
;( a mare is not really a mare)
Characteristics
large size
genital examination reveals normal vulva
speculum about 5 to 6 inches
complete blockage at vestibulovaginal conjunction
no external os of cervix
rectum examination shows no vagina, cervix, uterus & oviduct
gonads are symmetric in shape without indentation caused by ovulation fossa
Comments
male masquerading as a female
do testosterone analysis on plasma
If gonads are testes, secrete high [testosterone]
testes able to secrete Mullerian -inhibiting factor
do chromosomal analysis, verify XY sex chromosome complement
external genital tissues lack critical androgen receptors
absence of testicular input, ( Mullerian -inhibiting factor & testosterone) = lack of sexual differentiation
No treatment
Pregnancy And Parturition
Pregnancy
The Development Of An Embryo Involves Fusion Of An Oocyte And Spermatozoon Within The Oviduct.
Spermatozoa, stored concentrated in epididymis( change from aerobic to anaerobic metabolism).
Mature sperm can metabolize fructose.( lactose, glucose, dextrose , fructose = semen extender)
Cervical mucus help in sperm movement, thinning of mucus occur b4 ovulation → can estimate ovulation time.
White blood cells attracted to the uterine lumen to kill the “foreign” sperm in female genital tract.
“Capacitation”= removal of glycoprotein from sperm cell surface, which is the protection of sperm.
“Acrosome reaction”= release of hydrolytic enzyme from acrosomal cap; help to penetrate granulosa & zona pellucida of oocyte.
Hyaluronidase breakdown hyaluronic acid in the granulosa matrix.
Acrosin digest acellular coating around the oocyte.
Frozen sperm have reduced longevity.
Male gametes have twice the life span of oocyte.
Sperm are in “ ready to fertilize” state when reach oviduct.
Extension Of The Life Span Of The CL In Large Domestic Species And Cats Is Essential For Pregnancy Maintenance.
Embryo secrete estrogen to notify the endometrium about pregnancy.
“Trophoblastin’ produced in sheep and cattle have close relationship with “interferon”.
PGF2α synthesis suppressed ( in cow), mode of secretion modified from pulsatile to continuous ( in sheep).
No PGF2α pulsatile mode, CL life span extended.
Cat CL can last 35-40 days without pregnancy.
“Relaxin’ ( placental hormone ) support progesterone function.
Luteotropin (Choronic gonadotropin CG) are produced by trophoblastic cells of embryo.
Embryo must implant first in order to release CG.(24-48 hours after implantation)
Domestic animals use intestitial implantation.
Dogs and Cats use eccentric implantation which is less invasive.
Large domestic animals have minimal invasion of endometrium.
Rumminant use caruncles, Horse and pig use villus invasion.
Subclinical uterine infection/ Inadequate endometrial gland → interfere implantation.
cervix form the contamination barrier to protect uterus.
The Placenta Acts As An Endocrine Organ
Fetus interact with placenta to produce estrogen.
Primate placenta unable to produce estrogen from progesterone.
Placenta supplies “ pregnenolone’- immediate precursor of progesterone to the fetus.
“Fetal zone of adrenal cortex”-transform pregnenolone to C-19 androgen(dehydroepiandrosterone) and transport to placenta to be converted to estrogen.
Other species have placental enzyme that allow progesterone metabolied to estrogen.
Fetal cortisol induce the placental enzyme in sheep.
“Relaxin” prepared soft tissue of the pelvic canal for parturition, act synergistic with progesterone.
Relaxin is produced by CL for pig, cow,primates.
Equine Chorionic Gonadotropin (eCG)= “pregnant mares’ serum gonadotropin”
eCG enhance progesterone production by CL → luteinization.
Placental lactogen is a placental protein hormone.[Placental lactogen]↑, as [CG]↓ during pregnancy.( latter part of gestation)
Placental lactogen is somatotropic (GH effect) and lactogenic ( prolactin effect).
Parturition
Fetal Cortisol Initiates Delivery Through Increased Secretion Of Estrogen And Thus Prostagladin F2α
Progesterone maintain myometrium wall and promote tightly contracted cervix.
Estrogen stimulate production of “contractile protein” (↑contractile potential) and form “gap junction”( ↑ communication btw smooth muscle) on the uterine muscles.
Fetal adrenal cortex, hypothalamus & adenohypophysis initiate parturition.
Destruction of any 1 of the 3 organs→ prolonged gestation.
Fetal adrenal cortex( sensitive to ACTH)→ cortisol→ ↑ PGF2α release from uterus→↑ muscle contraction & relaxation of cervix.
Fetal cortisol induces placental enzymes (17-hydroxylase & C17-20 lyase),direct steroid synthesis away from progesterone to estrogen.
[Estrogen]↑,[PGF2α &PGE]↑= initiate parturition.
[PGF2α]↑ because [arachidonic acid substrate]↑.
Estrogen influence the phospholipase A making system.
Phospholipase A is a lysosomal enzyme, hydrolyse phospholipid→ release arachidonic acid.
PGF2α release intracellular Ca2+ in myometrium, binds to actin and myosin→ initiate contraction process.
PGF2α & PGE cause relaxation and dilation of cervix.
PGF2α cause cervix loss collagen fibers, by ↑ glycosaminoglycans.
Progesterone do not initiate delivery, but PGF2α cause luteolysis→ myometrial contraction.
Oxytocin promote uterus contraction.
Estrogen induces oxytocin receptor formation in myometrium when fetus enter pelvic canal.
Oxytocin is released by Ferguson reflex.
Relaxin seperate pubic symphysis through relaxation of interpubic ligaments.
For cow and sow = CL is source of relaxin.
[PGF2α]↑→luteolysis→[ progesterone]↓ →[relaxin]↓
For cat, dog , horse = placenta is soure of relaxin.
1st stage of parturition = fetus reach internal os of cervix, cervix open and fetus pass into pelvic canal.
2nd stage of parturition = actual delivery process with abdominal press ( contraction of abdominal muscles).
3rd stage of parturition = delivery of fetal membrane ( placental membrane).
Litter-bearing animals ( cats, dogs, pigs)= placental membrane came out immediately with the fetus.
Single-bearing animas ( horse, cattle)= placental membrane come out immediately or within several hours.
PGF2α important for placental membrane expulsion from uterus by myometrium contraction.
3.Clinical Correlations
Prolonged Gestation
Clinical examination
Holstein cow with 12 days overdue to gestation,artificial inseminated and found pregnant 35 days later. The cow has enlarged abdomen and the calf is large, no colostrum in the udder. The fetus is defective to initiate parturition. The fetus has abnormal hypothalamic-pituitary-adrenacortical system development, unable to synthesis cortisol that initiate parturition.Low cortisol concentration cannot initiate PGF2α synthesis, leads to inadequate stimulation for parturition and lack lactogenesis, indicates delayed colostral formation.
Treatment
The animal can respond to glucocorticoids. Administer glucocorticoid to substitute fetal cortisol to initiate endocrine activity that lead to parturition. Lactogenesis is usually initiated by glucocorticoid treatment.As it is a prolonged gestation, the calf is too big to be delivered, cesarean section will be performed when the cervix dilate due to the glucocorticoid treatment.The calf is not likely to survive due to inadequate adrenal secretion and this disease is an autosomal recessive inherited condition.