Lecture 8: Reproductive Pathology

Uterine Prolapse

• Most common in dairy and beef cows and ewes 

  • Less frequent in sows

• Tip of the uterine horn invaginates

• Factors that predispose to prolapse

  • Excessive traction to relieve dystocia (difficult birthing) or retained fetal membranes

  • Uterine atony

  • Hypocalcemia

  • Lack of exercise

  • Grazing estrogenic pastures

• Immediately after parturition

  • Cervix is open

  • Uterus lacks tone

• Treatment:

  • Remove placenta (if still attached)

  • Thoroughly clean endometrial surface +/- surgically repair any lacerations

• Reduce edema and aid reduction of the prolapse:

  • Apply sugar to the surface of the uterus

  • Rinse with hypertonic saline

• Epidural anesthetic

  • Administer before attempting to return the uterus to its normal position

• Standing – elevate uterus to level of the vulva

  • Use a tray or hammock supported by assistants

• Recumbent – position animal sternally to aid in the replacement of the uterus

  • Hind limbs extended caudally/Cow should be resting on its stifles

  • Position tilts pelvis cranially and ventrally to aid in the replacement of the uterus

• Apply steady pressure beginning at the cervical portion

  • Gradually work toward apex of the horns

  • Closed fist or palm - Do not use fingertips - avoid perforating uterine wall

• Standing – elevate uterus to level of the vulva

  • Use a tray or hammock supported by assistants

• Recumbent – position animal sternally to aid in the replacement of the uterus

  • Hind limbs extended caudally

  • Cow should be resting on its stifles

  • Position tilts pelvis cranially and ventrally to aid in the replacement of the uterus

• Apply steady pressure beginning at the cervical portion

• Gradually work toward apex of the horns

  • Closed fist or palm

  • Do not use fingertips - avoid perforating uterine wall

• Complications:

  • Laceration

  • Necrosis

  • Infection

• When treatment is delayed:

  • Shock, hemmorhage, and thromboembolisim 

• Uterine artery rupture

  • Excessive stretching of vessel

  • Weight of the prolapsed uterus

  • Sudden death

• Bladder and intestines may prolapse into everted uterus

  • These require careful replacement before the uterus is replaced

• Eversion and prolapse of the vagina

  • With or without prolapse of the cervix

  • Occurs most commonly in cattle and sheep (cows and ewes)

  • Usually occurs in mature animals in the last trimester of pregnancy

• Predisposing factors

  • Increased intra-abdominal pressure

    • Gravid uterus

    • Intra-abdominal fat

    • Rumen distention

  • Recumbent animals may contribute to eversion of the vaginal tissue

    • Increased intra-abdominal pressure

  • Stabled more often than pastured animals

    • Lack of exercise may be a contributing factor

• More predispoding factors:

• Increased circulating concentrations of estrogens and relaxin during late pregnancy

  • Relaxation & softening of the pelvic girdle, pelvic canal, and perineum

• Grazing estrogenic plants

  • Trifolium subterraneum

• Exogenous administration of estrogenic compounds

  • Growth-promotant implants

• Estrogenic activity of mycotoxin

  • Pigs

• Cows subjected to repeated superovulation for embryo recovery

  • Repeated exposure to supraphysiologic concentrations of estrogens

• Short tail-docking of lambs

  • Damage structures that support the pelvic girdle - eg, Coccygeus muscle

  • Predispose to vaginal prolapse if the tail is docked excessively

    • Level of the ventral skin fold, leaving two or three coccygeal vertebrae intact

• Breed predisposition

• Cattle - Brahman, Brahman crossbreds, Hereford

• Sheep - Kerry Hill, Romney Marsh

• Intussusception-like folding of vaginal floor

  • Cranial to the vestibulo-vaginal junction

• Eversion vreates discomfort, irritation, and swelling of exposed mucosa

  • Straining and more extensive prolapse

• Entire vagina may be prolapsed

  • Cervix inside

  • Bladder or loops of intesting within prolapsed vagina 

  • Urethra may be occluded

  • Bladder fills and enlarges

  • Hinfers correction of vaginal prolapse unless the bladder is first drained

  • Bladder may rupture

  • Potentially fatal

• Grade I: intermittent prolapse

  • Often visible only when recumbent

  • Vaginal tissues may appear normal

• Grade II: continuous acute prolapse of vaginal tissue

  • Always out

• Grade III: continuous acute prolapse of vagina, bladder, and cervix

  • Erosion of mucosal surface occurs

• Grade IV: chronic prolapse of either grade II or III

  • Resultant trauma, infection, or necrosis

  • Poor prognosis

• Treatment

• Epidural anesthetic

• Lavage vaginal tissues/cervix

  • Empty bladder

  • Lubricate vagina

  • Replace and hold in position until it warms

• Buhner suture — deeply-buried, circumferential suture

  • Placed around the vestibulum

  • Provide support at the point at which the initial eversion of the vaginal wall occurs

  • Purse-string suture should be tightened

  • Allow opening at the ventral commissure for urination

  • ~3–4 cm or 2–3 finger widths

• Buhner suture or horizontal mattress/shoelace pattern

• Placement of a retention device within the vagina

  • Tend to cause discomfort and further straining

Abortion

• Definition:

  • Artificial termination of pregnancy

  • After organogenesis is complete

  • Before fetus is viable

• Early embryonic death:

  • Pregnancy ends naturally before organogenesis 

• Stillbirth: 

  • Full-term fetus that is delivered dead

  • Compromised neonates, and occasionally mummified fetuses

• Occurance: 

  • Often follows initial acute infection

  • Infection may linger for weeks or months

  • Causative agent may not be found when abortion occurs

  • Post-mortem examination requires comprehensive testing

    • Herd outbreak: representative samples needed

    • Complete herd history is important!

• Expulsion:

• Follows fetal death by hours or days

• Lesions obscured by autolysis

• Sporadic instances of abortion are likely the result of noninfectious (eg, toxic or genetic) causes

Abortion Sampling: Diagnostics

• Complete fetoplacental unit in fresh condition

• Placenta and fetus: clean with water or saline

  • Pack in clean plastic bags

  • Chill (do not freeze)

  • Rapid transportation to diagnostic laboratory

• Maternal serum

• Basic set of samples:

  • Stomach or abomasal contents

  • Heart blood

  • Fluid from a body cavity

  • Unfixed lung, liver, kidney, and spleen

    • Laboratories may request: thyroid glands, thymus, heart, brain, abomasum, & stomach

  • Placenta + Dam’s serum

• Fresh tissue:

  • Submitted in 10% buffered formalin for histopathologic examination

  • Lung, liver, heart, kidney, spleen, brain, skeletal muscle, thyroid, adrenal glands, intestines, and placenta

• Why fetal stomach contents? Diagnostics

• Pathogens infect maternal placenta

• Enter amniotic fluid

• Swallowed by fetus

• Stomach contents obtained aseptically

• Best specimen for detection of fungi and most bacteria

• Isolation from stomach contents less contaminated

• Placenta - always heavily contaminated

• Serum samples:

• Could provide evidence of abortion caused by a particular agent

• Paired serum samples obtained 2 weeks apart

  • 10% of the herd or a minimum of 10 animals

  • Demonstrate seroconversion

  • Provide evidence of active infection in a herd

• Demonstration of a fourfold increase in antibody titer is required to prove active infection by a specific agent

• Single antibody titer in the dam is ineffective

Causes of Abortion

• Non-infectious 

  • Genetic factors – unknown incidence

  • Twinning - horses

  • Heat stress/High maternal temperature

  • Toxins

    • Ponderosa pine

    • Locoweed

    • Broomweed

    • Moldy sweet clover/mycotoxins

    • Nitrates/nitrites

  • Drugs

    • Estrogen

    • Steroids

    • Levamisole

    • MLV vaccines

  • Dietary

    • Copper/Selenium/Vitamin A/Magnesium

Causes- Infectious Agents

• Bluetongue 

• Bovine Viral Diarrhea virus – BVD-V

  • Border disease – sheep – Pestivirus related to BVD-V

• Brucellosis

• Campylobacteriosis – “Vibriosis” or “Vibrio”

• Chlamydiosis

• Infectious Bovine Rhinotracheitis (IBR) – Bovine Herpesvirus 1

• Leptospirosis

• Listeriosis

• Mycosis

• Neosporosis

• Q-Fever

• Salmonellosis

• Toxoplasmosis

• Trichomoniasis

Non-Infectious Causes

• Twinning – horses

  • Twins are fatal in most cases

• Heat stress

  • Ambient temperatures

  • Internal body temperatures

    • Swine affected >> sheep/goats >> cattle

• Toxins

  • Ingested by dams

  • Some are dose-dependent

• Drugs – accidental or induced?

Brucellosis

• Brucella abortus

  • “Bang’s Disease” or Undulant Fever in humans

  • 80% abortion rate in exposed animals

  • About 7 months gestational age

  • Occurs 2 weeks – 5 months after exposure

• Placentitis

  • Cotyledons – normal – necrotic

  • Red/yellow, wet, leathery appearance

• Autolytic fetus with bronchopneumonia

• Diagnosis:

  • Maternal serology

  • IFA staining – placenta,fetus

  • Culture of B. abortus from fetal components or uterine discharge

• Prevention:

  • Calfhood vaccination with RB-51 live vaccine

  • Licensed, accredited veterinarian

• Avoid consumption of raw milk

• Federal eradication program

Vibrio

• Campylobacter fetus venerealis

  • Venereal disease

  • Infertility

  • Early embryonic death/Abortion between 4 and 8 months of gestation

  • Cattle, sheep

• Transmission

  • Ingestion → hematogenous spread to placenta

    • Abortions occur during last half of gestation

• Fetus:

  • Fresh - partially expanded lungs

  • Severely autolyzed

  • Mild fibrinous pleuritis + peritonitis/Bronchopneumonia

• Placentitis

  • Mild - hemorrhagic cotyledons + edematous intercotyledonary area

• Diagnostics

• Presence of late-gestation aborted fetus

• Darkfield microscopy → abomasal contents or culture of placenta

• Treatment

• Tetracyclines – prophylactic use in endemic areas

  • Resistance observed

  • VFD regulations prohibit use without VPR/prescription

• Prevention/Control

  • Artificial insemination

  • Vaccination

• Campylobacter spp are zoonotic***

• C jejuni is an important cause of enteritis in people***

Leptospirosis

• 7 different species of Leptospires

  • >200 recognized serovars

  • L interrogans Serovars causing last-trimester abortions:

    • Grippotyphosa

    • Pomona – pigs 

    • Bratislava – pigs 

    • Canicola

    • Icterohemorrhagiae 

• L borgpetersenii serovar Hardjo type hardjobovis 

• L interrogans serovar Hardjo type hardjoprajitno

• L interrogans serovar Pomona 

• L kirschneri serovar Grippotyphosa

• Lifelong infections occur

  • Adapted to survival in kidney + repro tracts

  • Reduced conception rates/fertility

• Clinical signs:

  • Asymptomatic – healthy individuals 

  • Abortions – especially late-gestation

  • Jaundice, pyrexia, convulsions, incoordination 

  • Chronic renal failure, reproductive inefficiency

  • Mastitis/Agalactiae 

• Fetus:

  • Autolyzed

  • Mummification

  • Maceration

  • Stillbirths

  • Weak neonates (calves, piglets)

• Diagnosis:

  • Fetal submission

  • Maternal serum – paired samples!

• Treatment: 

  • Carrier animals – single dose of tetracycline, tilmicosin, ceftiofur or amoxicillin

• Control:

  • Eliminate sources of infection

  • Multivalent vaccines

    • Primary dose followed by booster dose

    • Booster q 6 months in endemic herds/areas

• Leptospirosis is zoonotic**

• Urine + millk may be infective > 3 months after infection**

• L. hardjo infective for lifetime of animal

Neospora

• Neosporum caninum 

  • Protozoan parasite

  • Worldwide distribution

• Most common cause of abortion in beef/dairy cattle

  • Parts of the US

• Source of infection:

  • Canines – dogs, coyotes, foxes, wolves

    • Infect feed sources

  • Fecal-oral transmission

• Clinical signs:

  • Abortion 

    • Autolyzed fetus

    • Mummified with no gross lesions

  • 4-6 months gestation

  • Sporadic or storms

  • Repeat abortion

• Calves:

  • Asymptomatic 

    • Congenitally infected

  • Paralysis/proprioceptive deficits

• Diagnosis:

  • Abortion submission

  • Maternal serum

  • Herd serum screen

• Non-suppurative inflammation

  • Brain, heart, skeletal muscles

• IHC stain

• PCR assay

• Treatment - NONE

• Transmission and Control:

  • Vertical transmission is possible!

  • Organisms activated during pregnancy

    • Infect fetus across placenta

• Strict hygiene

  • Protect feedstuffs

• Vaccines available

Q-Fever

• Coxiella burnetii 

  • Important cause of bovine + ovine + caprine abortion 

  • Called “Q-fever” = “Query”

  • Rickettsial organism

    • Stable, resistant

    • Spore-forming

• Clinical signs:

  • Late-term abortions 

  • Stillbirths/Weak lambs 

  • > 50% of the flock may be involved 

  • Placenta 

    • Gray-brown exudate 

    • Thickened intercotyledonary areas 

    • Necrotizing vasculitis 

    • Chorionic epithelial cells distended by small, coccobacillary organisms 

      • < 1 mcm in diameter

  • Infection involves only the placenta

• Diagnosis:

  • Submission of fetal materials

    • Organism sequesters in uterus, placenta, mammary glands, milk

    • Also found in repro tract of males

  • Maternal serum

  • Identification of C burnetii 

  • IHC, PCR, or by isolation

    • Blood, milk, tissues

• Control: 

  • Investigate abortions

  • Good hygiene

  • Avoid windy conditions when spreading feces or aborted placenta, etc

  • Identify carriers

  • Wear PPE

  • Vaccinate animals

  • Avoid raw milk

• Coxiella is zoonotic

• Q-Fever in people can be fatal

Toxoplasmosis

• Toxoplasma gondii

• Ruminant – cat cycle

  • Oocysts can survive 18 months if cool, wet

  • Sheep and goats – seldom acute disease, outbreaks of late abortion, weak lambs, pyometra

  • Cattle – minor, more resistant

• Immunity – no additional abortions or clinical signs if re-exposed

Trichomoniasis

• Tritrichomonas foetus

  • Protozoan parasite

  • Venereal disease

• Clinical signs:

  • Infertility

  • Irregular calving intervals

  • Infertility

  • Abortions

  • Pyometra

  • Bull is clinically normal! 

• Transmission:

  • Direct transmission during breeding

  • Infected semen via artificial insemination

• Worldwide distribution

• Diagnosis:

  • Culture – specific media required!

    • Cows – vaginal swabs

      • Pyometra fluid post-abortion

    • Bulls – smegma sample from preputial washes

  • PCR – fast results

• Treatment:

  • Cows may clear infection if rested/no exposure

  • Bulls are infected for life

    • Remove bulls > 2-3 yrs old

• Prevention:

  • Biosecurity

  • Fences

  • Young bulls

  • Purchase don’t borrow!

  • Vaccinate

Mycotoxins

• Zearalenone and zearalenol 

  • Estrogenic mycotoxins 

  • Interfere with conception and implantation 

  • Cause infertility, embryonic death, and reduced litter size – rarely abortion 

• Source: Fusarium spp 

  • Fungi are extremely common and often contaminate growing plants + stored feeds 

    • Corn (maize), wheat, and barley, and forage (silages) are commonly contaminated

  • Fusarium species can produce zearalenone

• Zearalenone - reproductive toxicosis in sexually mature sows 

  • Inhibits secretion and release of follicle-stimulating hormone (FSH) 

  • Results in arrest of preovulatory ovarian follicle maturation

• Young males, both swine and cattle

  • Atrophy of the testes

• Ewes - reduced reproductive performance 

  • Reduced ovulation rates and numbers of fertilized ova

  • Markedly increased duration of estrus 

  • Abortion or premature live births

Prolonged Gestation

• What is “normal” gestation length?

  • Cattle =

  • Sheep/goats = 

• Add extra estrus cycle to length of gestation 

• Etiology:

  • Defective hypothalamic-pituitary-adrenal axis (HPA)

    • Prevents initiation of parturition/end of gestation

    • Often undetected

• Result of HPA defect:

  • Fetal mummification – no signal to maternal HPA axis

  • Genetic – fetal gigantism

  • Infectious

  • Iatrogenic

  • Phytogenous toxins

• Diagnosis:

  • Deviation from known length of gestation

  • Appearance of fetus

    • Necropsy!!

  • Appearance of dam:

    • Enlarged abdomen 

    • Mammary gland development

    • Vulvar edema

    • Sacrosciatic ligament relaxation

• Treatment:

  • Induce parturition

  • Exogenous corticosteroids

    • Live fetus only – intact HPA

  • Prostaglandin

    • Live or dead fetus

  • Supportive care of dam

  • Goal – deliver fetus with minimal injury to dam

• Assess viability of fetus

• Assess fetal-pelvic proportions – will that calf fit through that pelvis??

• Cesarean section

• Fetotomy

• Vaginal delivery 

Retained Fetal Membranes

• Retained placenta

• Failure to expel placenta 

  • Horses within 3 hours

  • Cattle within 24 hours

• Normal time frame:

  • Horses – Immediately 

  • Cattle – 3-8 hrs  

• Look for the placenta after parturition!

  • Sometimes retained inside the uterus

• Diagnosis:

  • Straightforward – History + clinical signs – protruding membranes

• Manual removal is not recommended

  • Trim excess tissue 

• No treatment – membranes expel within 2-11 days

• Treat concurrent systemic illnesses:

  • Mastitis

  • Pneumonia

  • Ketosis

  • Displaced abomasum

• Prevention – manage dry cow diets

• Economic cost of metritis in dairy cattle: $386/case

  • Decreased milk yield, increased time to next pregnancy, associated periparturient diseases, increased culling risk

Retained Fetal Membranes in Mares

• Emergency

  • Expulsion should occur within 3hrs after parturition

• Low incidence

  • High incidence of reoccurrence

• Diagnosis:

  • Examine entire placenta to look for missing pieces

• Treatment:

  • Manual removal is discouraged

  • Oxytocin

    • Bolus injections/slow infusion

  • Uterine lavage

  • Antimicrobials 

Metritis/Endometritis/Pyometra

• Contagious Equine Metritis

  • Highly contagious

  • US is free from CEM

• Animal Hx: infertility!

  • Post-breeding – copious mucopurulent discharge from vulva

    • Clears within 2 weeks

  • Subclinical carriers develop

• Diagnosis:

  • Bacterial C/S

• Treatment: ineffective

  • Wash genitalia SID X 1 week – chlorhexidine scrub

Endometritis

• Endometritis 

• Mares – most common repro disease

• Etiologies:

  • Repeated breedings = inflammatory response

  • Chronic infections

  • Poor conformation

  • STD

  • Degenerative (aging)

• Endometritis diagnosis:

  • Culture + Sensitivity

  • Ultrasound

  • Uterine biopsy

• Treatment:

  • Uterine lavage with antibiotics

  • Oxytocin

• Prevention:

  • Breed mares as few times as possible during a cycle

  • Correct conformational problems

    • Surgery – Caslick’s procedure

Equine Coital Exanthema

• Etiology: Equine Herpesvirus 3 (EHV-3)

  • Transmitted in acute phase soon after infection

  • Highly contagious

    • Worldwide distribution where breeding mares live

• No systemic illness, infertility, or abortions result

• Issue is economical

  • Delayed conception

  • Increased expenses

• Clinical signs:

  • Lesions on vulva, vaginal mucosa, perineal skin, +/- teats & nasal mucosa, penis, prepuce

  • Secondary bacterial infections

• Diagnosis:

  • Clinical signs

  • PCR assay

• Treatment

  • No breeding/exposure to infected individuals

  • Topical antibiotics to prevent 2` infections