Theriogenology Week 8 PDF

THERIOGENOLOGY WEEK 8 Ashley Vasel mare infertility endometritis endometritis = inflammation of the endometrium clinical signs & diagnosing major contributor to equine infertility exaggerated and persistent predisposing factors age, cervical disorders (fibrosis, laceration) endometrial score – fail...

THERIOGENOLOGY WEEK 8 Ashley Vasel mare infertility endometritis endometritis = inflammation of the endometrium clinical signs & diagnosing major contributor to equine infertility exaggerated and persistent predisposing factors age, cervical disorders (fibrosis, laceration) endometrial score – fail to uterine clear/contract pathology when inflammation doesn’t stop INFLAMMATION = persistent breeding induced endometritis INFECTION = due to bacteria or fungus endometrial/intrauterine edema / fluid accumulation fluid prevents normal mucocillary clearance of pathogens in uterus inflammation of endometrium – see on cytology or biopsy (> 5 PMN cells per field) shortens their cycle (shorter diestrus) inflammation → prostaglandin → shorter cycles persistent post-breeding endometritis ALL MARES REACT to foreign semen treatment (reduce inflam., improve environ.) post-breeding endometrial inflammation is NSAIDs normal! normal series of events selective cox-2 inhibitors = firocoxib, robenacoxib, deracoxib NON-COX-2 may mess with reproduction sperm → inflam. → influx of immune cells and incr. uterine motility → neuts phagocytose excess small doses of oxytocin (ecbolic) sperm PGF2a (ecbolic; can interfere with CL development!) getting rid of uterus contamination SHOULD stop in 24-36hrs post breeding pathology = inflammation > 48h post-breeding REMEMBER: negative culture – this isn’t infectious! post-breeding lavage – LRS (not spermicidal) corticosteroids: pred, dexamethasone watch out for laminitis in old mares immunomodulators (PRP, stem cells) infectious endometritis d/t bacteria and fungus diagnosis extends beyond the estrus period #1 *Streptococcus zooepidemicus just ongoing infertility d/t impaired uterine defenses horses may have conformation defects probs with cervix making it a shit barrier positive on cytology #2 E. coli also Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus culture cytology low volume lavage turbidity of fluid indicates inflammation too vet prep J treating infectious endometritis biofilm treatment aggregate of microorganisms adhering to uterine lavage 1st to remove exudate w/ LRS each other and to a mucosal surface in a mucoid matrix film reduces bacteria’s susceptibility to antimicrobials dispersing biofilm solvents and mucolytic agents will disrupt biofilm and improve antimicrobial penetration DMSO N-acetylcysteine – mainstay of tx, uterine infusion choose appropriate antibiotic through sensitivity test, tx during estrus for 3-5 days intrauterine infusion of antimicrobials caution some (enrofloxacin) may result in necrosis or fungal endometritis or do systemic antibiotics ecbolics, anti-inflam., corticosteroids NOTICE, treatment is very similar to post- breeding endometritis – the difference is here something is infectious so we are using an antibiotic too!!! fungal endometritis predisposing factors treatment morphological problems correct morphological disorder prolonged antibiotics antifungals – systemic, intrauterine diagnosis rare, most common is Candida culture cytology can use intrauterine: nystatin, amphotericin B uterine lavage + acetic acid ecbolic (oxytocin, PGF2a) contagious equine metritis Taylorella equigenitalis venereal disease CS: mucopurulent discharge from vulva diagnosis culture clitoral swab treatment lavage with chlorhex quarantine then PCR test to be sure they are negative chronic degenerative endometritis pathologic fibrosis in the endometrium decreases the chance to carry a pregnancy to term reduces myometrial contractility → fluid accumulates → endometritis can cause endometrial cysts no treatment, just try and improve the uterine environment Fibrosis – Endometrial Biopsy < 10% chance if grade 3!!! endometrial cysts assoc. with periglandular fibrosis of the endometrium dilated lymphatics d/t occlusion can complicate pregnancy diagnosis bc they look like an early pregnancy cyst is not perfectly round, embryo is cysts wont move, embryo can cyst won’t grow, embryo will messes with maternal recognition of pregnancy embryo cannot move around bc cyst is in the way → no MRP fibrotic area doesn’t allow placentation → abortion can ablate with laser or punch with biopsy so they drain could just remove but usually they come back pyometra rare pus in uterus won’t show CS cervical pathology / damage → failure of drainage → secretions build up → infected treatment correct cervical disorder or else it will just occur again antibiotics uterine lavage pyometra species comparison horse cow cervical damage preventing uterine drainage early post-partum ovulation in the face of continuing uterine infection uterine tumor rare surgically remove hysterectomy ovulation failure hemorrhagic anovulatory follicle normal sized follicle that follicles grow A LOT – never ovulates was never ovulated persistent anovulatory follicle follicle can regress or luteinize causes d/t age or cyclicity transition hemorrhages inside follicle → lumen fills with blood on U/S you see an anechoic follicle with hyperechoic lines inside (fibrin) no need to treat just wait it out could aspirate and inj. hCG to speed up the process causes d/t cyclitiy transition used non-COX-2 NSAIDs (flunixin meg aka banamine, or phenylbutazone) recall, NON-COX-2 may mess with reproduction!!!! stress (high dopamine) anabolic steroids vet prep J vet prep J ovarian hematoma uncommon occurs AFTER ovulation – she did ovulate!! bled so much she formed a hematoma could have a fertile cycle and have a big hematoma ovary **ovarian granulosa theca cell tumor** most common equine ovary tumor horse CS depends on hormones being produced androgens (testosterone) → aggression, voice change, behavior stallion-like, a mare will show estrus signs towards this horse progesterone → not showing signs of cyclicity estrogen → consistent signs of estrus that do not go away find 1 large ovary and 1 small ovary d/t steroid production by tumor neg. feedback to FSH and LH resulting in no stimulation to contralateral ovary ovulation fossa is obliterated tumor has rounded ovary so fossa is gone ultrasound large honeycomb appearance diagnostics lots of circulating testosterone lots of inhibin – inhibin is made by GCT! AMH treatment surgically remove ovary contralateral ovary will resume function great prognosis return to fertility depends when in the season this took place d/t the mare’s natural seasonality vet prep J vet prep J uterine tube masses cause unexplained infertility masses come from the follicular fluid when the mare ovulated the mass in the oviduct occludes it preventing embryo to move to uterus preventing sperm from entering “owner reports flawless fertility and ovulation but is not getting pregnant” treatment give prostaglandin E to treat blockage and fix mare’s infertility recall, equine embryos secrete PGE2 which promotes passage of the embryo through the oviductal isthmus into the uterus cervical disorders laceration during foaling tx: sx cervical incompetence – fibrosis d/t excess manipulation (embryo flushing) or several gestations tx: manage the uterine fluid accumulation bc she cannot push it out cervical occlusion tx: sx urovagina reflux of urine into vagina when mare is in estrus cervix is open and on the bottom → urine goes in → cause endometritis diagnosis increased eosinophils (inflammatory cells) on cytology & biopsy check pH (basic) to see if its urine or not treat with surgery perineal lacerations first degree usually has a pneumovagina second degree third degree connection with rectum and vagina occurs during foaling treatment surgery pneumovagina air accumulation/pulling into the vagina perineal body disrupted – laceration infection and chronic inflammation of the vagina and uterus may occur endometritis is common due to the presence of feces and debris into the vagina associated with differences in intra-abdominal, vaginal and uterine. treatment caslick surgical procedure aka vulovoplasty ICVA exam this is a BAD perineal body conformation check perineal body conformation!!! want a vertical vulva that closes well poor conformation results in fecal contamination and infection risk of pneumovagina most overlooked lesion in equine repro L persistent hymen incidental finding has holes that allow drainage IF imperforate persistent hymen aka no drainage see in filly at 15mo bulging hymen at vulva d/t accumulation (esp. at laying) colicky easily treated ➝ make incision ➝ fluid drains ➝ solved vaginal varicose veins no big deal causes intermittent vaginal bleeding tx: cauterize often assoc. with pregnancy “vaginal hemorrhage in older mare” X0 Chromosome Abnormality (turner’s in humans) common congenital chromosome abnormality in mares that causes cycle failure infertile! owner reports she has never been able to get pregnant not sure why normal external genitalia gonadal dysgenesis (small ovaries) small stature – like a pony diagnose via karyotype to see a lack in a chromosome “horse may look scruffy, some may look great” Mosiacism population of cells with normal chromosomes (XX) and one with an abnormal set (X) two different cell populations within an individual these mares cannot get pregnant Intersex external genitalia does not match with chromosomes causes of abnormal cyclicity equine Cushing’s (PPID) – endocrine disorder mare with long hair and abnormal cyclicity (long cycles), not responding to prostaglandin they cannot carry babies to term equine metabolic syndrome (fat mares) – endocrine disorder pretty much diabetes – so exercise, modify diet long cycles, not responding to prostaglandin season poor BCS age later first ovulation of season longer follicular phase results in longer cycle granulosa (thecal) cell tumor persistent endometrial cups PHYSIOLOGY & DIAG NOS IS maternal recognition of pregnancy pregnant and non-pregnant cycle similarly for the first 14 days suppression of PGF2α release in pregnant mares mechanism not completely understood compared to other animals conclusion: mare in silly goofy mood MRP depends on the movement of the embryo throughout the uterus! preg. will fail if the embryo cannot move through the uterus maternal recognition of pregnancy by species ruminants (cow, ovine, caprine) sow mare bitch & queen interferon tau (IFN-t) will inhibit oxytocin receptor synthesis, preventing oxytocin from triggering PGF2a synthesis 4 positive signs of pregnancy amniotic vesicle fetal membrane slip placentomes fetus blastocyst produces estradiol re-routes PGF2a release into uterine lumen where it is destroyed PGF2a changed from endocrine to exocrine secretion PGE2 produced by the embryo blastocyst trans-uterine migration reduced synthesis of PGF2a ➝ converted to PGF2a exocrine doesn’t require a signal, the CL will be there regardless if they are pregnant or not relaxin secretion is a pregnancy indicator pregnancy physiology embryo capsule fertilization in uterine tube unique to equine embryo enters uterus around 6d after fertilization transport depends on PGE2 polysaccharide-rich membrane between trophectoderm and zona pellucida unfertilized oocytes not transported through uterine tube forms soon after embryo reaches uterus responsible for preserving round shape of embryo and maintaining some rigidity, necessary for uterine migration disappears after day 23 mobility phase equine embryo migrates through both uterine horns and body several times a day up to 18 horn changes per day embryo fixation movement is mediated by uterus /some signal from embryo? embryo ceases migration at d 16 post-ovulation movement is maximal around days 10 – 12 big embryo “fixed” at base of 1 uterine horn prevention of movement results in pregnancy loss now can block luteolysis J not related to side of ovulation – can fix at either horn! implantation (gradual process) starts at d 25 → microvilli d 38-40 → microcotyldeons d 45 placenta = diffuse, epitheliochorial, adeciduate, microcotyledonary the pregnant mare endometrial cups unique to equines chorionic girdle yolk sac pregnancy loss allantois cups fetal embryo chorionic girdle cells migrate into maternal endometrium at ~35d to create the cups the endometrial cups produce equine chorionic gonadotropin (eCG) detectable at d 35, peaks at d 60, disappears d 100-150 eCG aka pregnant mare serum gonadotropin, acts like LH stimulating ovarian function, CL formation, and progesterone secretion the production of the fetal tissue cells (cups) result in a maternal immune response because they are foreign to mom mom immune response → results in necrotic tissue b/w maternal endometrium & fetal chorion → resolve cups mares who have previously been preg. have a stronger immune response against the cups and they resolve faster IF cups are established when pregnancy fails, the cups will persist for their normal lifespan.... viable THEREFORE..... the cups keep making eCG mare will fail to cycle UNTIL the cups are resolved / disappears (100-150d) – horse uterus limbo secondary corpora lutea commonly mis-dx’d as ovarian tumors & remove large multifollciular ovaries L multiple follicles luteinize w/o ovulation thx to eCG → mare now has multiple corpora lutea → 1o and 2o CL’s will produce progesterone → 1o and 2o CL degenerate at day 150 of pregnancy → now progestin prod. is by the placenta hormones fetoplacental progestin production placenta produces a form of progesterone = 5-alpha-pregnanes fetoplacental estrogens equine specific – equilin, equilenin mare fetus fetal gonads (ovary or testes) produce androgens → converted into estrogen in the placenta high estrogens indicate a healthy fetoplacental unit J can be administered orally survive pass through liver relaxin produced by placenta (mainly) AND CL in mares – imp. for parturition!! sooo we can use ovariectomized mares as recipients BUT in cow relaxin comes just from the CL, if they are ovariectomized they cannot be receipients and give birth ovariectomized mares as embryo recipients very effective J prime with P4 so uterine development is same as donor maintain exogenous progesterone (P4) until day 120 after that placenta provides sufficient support baby will still have normal foal heat diarrhea d/t normal microbiome gut changes vet prep J zuku J VET PREP J vet prep J DIAG NOS ING PREGNANCY & E M B RY O - F E T A L DEVELOPMENT diagnosing pregnancy no return to estrus ultrasound – preferred method!!! vaginal exam vesicle visible at d 9 in most, d 10 in all cervix is tightly closed and lifted off the floor transrectal palpation = tight uterine tone, bulge at ventral part of horn routinely do at 14d more accurate, will be an obvious vesicle by then lab dx – hormone assays have risk for false + / equine chorionic gonadotropin (eCG) false positives if cups are established even tho pregnancy is lost false negatives if cups disappear too quickly – mares who had multiple pregnancies ID twins and treat! - will see 2 CL’s! estrone sulfate (estrogen) embryo proper 20/21d heartbeat at 25d sexing at 60d – very unlikely loss after 60d indicates a healthy fetus and placenta (sulfunation in placnta) useful after 90d J zuku J day 9-10 embryo visible on U/S perfectly rounded black circle in middle below the white line is the tube day 12 still round and getting bigger day 16 fixation – no more moving around embryonic disc ventral, yolk sac above day 18 no longer round bc it isn’t moving anymore! day 30 day 22 can see embryo white speck at bottom is embryo proper yolk sac and allantois day 24 below the embryo there is a black spot → beginning of allantois day 26 allantois growing more, yolk sac is receding yolk sac loses its circular shape embryo is between yolk sac and allantois embryo is in middle equal in size day 40 can see embryo’s structures vet prep J cyst vs. embyro on ultrasound in the early stages you could confuse a pregnancy with an endometrial cyst embryo perfectly round mobile doubles in size everyday in early stages cyst irregular immobile does not grow free fluid in the lumen diffuse, all over the place vs. embryo is round with a capsule the embryo’s development notice after fixation (d 16) it loses its roundness allantois is lifting embryo up day 28-30 = embryo halfway up sex determination with U/S can sex on U/S at 60d genital tubercle is a bright echo on U/S penis = between legs, moves cr. towards the umbilicus male female clitoris = migrates cd. below base of the tail B-mode (brightness) can use at 110-180d, but scanning for this is trickier bc they are bigger, harder to locate tiny thang doppler is very helpful! male = central v. of testicle female = circular bloodflow around gonad at 110-120d, everything is well devel. BEST for sexing article with extra pics: https://aaep.org/sites/default/files/issues/proceedings-10proceedings-z9100110000323.pdf live video: https://www.youtube.com/watch?v=i6y6749RLyI&t=31s TWINS **twins** twin ovulation is common twin reduction ovulation can be synchronous (same day) or asynchronous 14-15d, max 30d = manual reduction aka crushing 1 twin, saving other do not want after 30d of pregnancy (dangerous!) mare’s placenta cannot support both very few twin pregnancies survive to term anyway (die, mummify, expelled) – causes “non-infectious” abortion! could spontaneously reduce but do not rely on this – intervention is preferred! literally crushing with fingers, can feel it pop could do with U/S probe by pushing down very high success rate J other twin will survive to term 30-60d = transvaginal U/S guided puncture aspirate allantoic fluid of twin, will probably lose other fetus 60-90d = fetal decapitation / cervical dislocation making small hole in abdomen → uterus → find fetus → rock head and break neck → decapitate amazing survival rate vs. both U/S guided procedures > 100d = intracardiac inj. using transadominal U/S vet prep J PREGNANCY FAILURE pregnancy failure the mare signs of impending loss about 10-20% pregnancies dx’d before 20d (2wks) are lost small for age of embryo (not growing) – if smaller than you’d expect, investigate! prob will lose preg. most losses occur before 60d anembryonic vesicle (vesicle without an embryo) older mares more likely – > 15-16yo esp. before pregnancy is even dx’d (before d 14) defect in oocyte not uterus L – hence why they are great embryo recipients aka blighted embryo hence why it is imp. to check for heartbeats at d 25 fixing in abnormal location and orientation embryonic death endometrial edema during pregnancy endocrine – P4 failure therefore shitty CL (rare) ABORTION – losses after 60d (cont. on next slide) endometritis → endometrial fibrosis salpingitis, stress, toxins 5-15% of pregnancy loss is accepted, greater than 15 we need to investigate!! genetic / chromosomal abnormalities samples whole fetus and placenta liver, lung, kidney, spleen stomach fluid – fetus inhales amniotic fluid! maternal serum – useful only if pooled