FAILURE of PREGNANCY in MARES

Reproduction in horses is all about the delivery of a live foal! Before you get all excited about looking at the placenta and fetus, know the normal structures. Check out these of my web pages. Normal functional anatomy of placentas and normal equine placenta.

The foaling rate of a large number of mares is about 50-60%. Failure of pregnancy in horses is high!

In a study of a large number of stallions and mares, Lane et al (2016) found that 67% of mares foaled.

 

Lane EA, Bijnen M, Osborne M, More SJ, Henderson I, Duffy P, Crowe MA. Key Factors Affecting Reproductive Success of Thoroughbred Mares and Stallions on a Commercial Stud Farm. Reprod Domest Anim. 2016; 51: 181-187.

General Failure of Pregnancy

Embryonic mortality

Embryonic mortality is defined as the death of the embryo. The general point of separation between embryo and fetus is either when the conceptus begins to move, or when it attains the phenotype to allow identification of the species.

Little is known of embryonic mortality, however there are some principles and possibilities. These will be discussed here.

Embryonic mortality is traditionally divided into early and late embryonic mortality. Early embryonic mortality is considered to be related to the health of the uterine tube and endometrium. Endometritis has a major effect in the mare. Late embryonic mortality can have a variety of causes including genetic and epigenetic anomalies.

The embryo spends some time in the uterine tube. Lesions of the uterine tube are not well described. Partial obstruction from dead embryos, debris or inflammation can prevent pregnancy.

Once in the uterus, uterine environment becomes very important. The embryo produces a substance that allows Maternal Recognition of Pregancy (MRP). The embryo must move throughout the uterus and endometrial cysts, foreign objects, adhesions, exudates/luminal fluid, endometrial edema and abnormal motility of the myometrium will block this. Embryonic loss will result.

The endometrial cups are formed about day 36-38. Failure of formation will result in loss of the conceptus at about day 80-95. This is why cross species abortion occursdie.

Wilsher S. The uterus and early pregnancy failure in the mare. Eq Vet Edu 2019; 31:214-224

Abortion

Abortion is failure of pregnancy in the fetal stage. There are myriad causes and these are detailed below in the SPECIFIC CAUSES of FAILURE of PREGNANCY.

Fetal maceration

Maceration of the equine fetus is a rare occurrence. Mostly, only fragments of bones remain. The initial cause of fetal death is seldom identified.

McNaughten JW,  Wallace RC. Theriogenology Question of the Month. Jv Amer Vet Med Assoc 2019; 254: 209-211

 

 

Reviews

There are several large reviews of failure of pregnancy so that the number and type of causes of failure of pregnancy can be determined.

Smith et al (2003) reported on 1252 fetuses and neonatal foals over a 10 year period in the UK. They found the following:

39% had umbilical cord lesions of which torsion was 33% and 3% were cervical pole necrosis

10% placentitis

7% Equid herpesvirus infection

6% twinning

14% stillbirth

3% were neonatal infections in the absence of placentitis.

8% were no diagnosis

 

 

 

Smith KC, Blunden AS, Whitwell KE, Dunn KA, Wales AD. A survey of equine abortion, stillbirth and neonatal death in the UK from 1988 to 1997. Equine Vet J. 2003; 35: 496-501.

 

Pozor M. Equine placenta – A clinician's perspective. Part 2: Abnormalities. Equine vet Educ 2016; 28: 394-404

SPECIFIC CAUSES of FAILURE of PREGNANCY

Non-infectious

Maternal causes of failure of pregnancy

Endometrial fibrosis

Endometrial changes including endometrial fibrosis alters the mileu of the fetoplacental unit. This affects both hemotrophic and histotrophic nutrition.

Uterine neoplasia

Canisso et al (2013) reported on a mare with failure of pregnancy that had a uterine lymphoma.

 

Canisso IF1, Pinn TL, Gerdin JA, Ollivett TL, Buckles EL, Schweizer CM, Ainsworth DM. B-cell multicentric lymphoma as a probable cause of abortion in a Quarter horse broodmare. Can Vet J. 2013; 54: 288-291.

 

Anomalies of fetus

Congenital hydrocephalus

Internal hydrocephalus

Non communicative

Obstruction of mesencephalic aquiduct (Sylvius)

Obstruction of Foramen of Monro a (interventricular)

Obstruction of foramina of Luschka (lateral apeture of 4th ventricle

Communicative type

Friesan foals with hydrocephalus have obstruction of the jugular foramens and cerebral vessels filled with blood. It is autosomal recessive inheritance. There is a nonsense mutation in B3GALNT2.

Other breeds, such as Belgian draft horses can have the same mutation.

Kolb DS, Klein C. Congenital hydrocephalus in a Belgian draft horse associated with a nonsense mutation in B3GALNT2. Can Vet J. 2019; 60: 197-198.

Sipma KD, Cornillie P, Saulez MN, Stout TA, Voorhout G, Back W. Phenotypic characteristics of hydrocephalus in stillborn Friesian foals. Vet Pathol. 2013; 50: 1037-1042.

 

External hydrocephalus

Increased production

Reduced uptake

Craniofacial anomalies

There are myriad anomalies of the skull.

Meloschisis (bilateral oblique facial clefts) was reported by Agerholm et al (2017)

 

Agerholm JS, Pedersen HG, McEvoy FJ, Heegaard S. Bilateral oblique facial clefts, rudimentary eyes and hydrocephalus in an aborted equine foetus. Reprod Domest Anim. 2017; 52(4): 692-695

Chromosomal/genetic/inherited

Chromosomal abnormalities

Genetic abnormalities including chromosomal translocations are possible causes of failure of pregnancy, usually early embryonic mortality. It is called Repeted Early Embryonic Loss (REEL).

Ghosh et al (2016) reported on a case where the Arabian mare had an autosomal translocation. She had REEL.

 

Ghosh S, Das PJ, Avila F, Thwaits BK, Chowdhary BP, Raudsepp T. A Non-Reciprocal Autosomal Translocation 64,XX, t(4;10)(q21;p15) in an Arabian Mare with Repeated Early Embryonic Loss. Reprod Domest Anim. 2016; 51: 171-174.

Glycogen storage disease - Glycogen branching enzyme deficiency

About 3% of horses with glycogen branching Enzyme deficiency abort. Most die in the neonatal and post weaning periods - up to 18 weeks.

Affected horses have spherical or ovoid inclusions in skeletal muscle. These are PAS +.

 

Render JA, Common RS, Kennedy FA, Jones MZ, Fyfe JC. Amylopectinosis in fetal and neonatal Quarter Horses. Vet Pathol. 1999; 36: 157-160.

Polymorphisms of p53

Leon et al (2012) reported on a mare that had repete early embryonic loss (REEL). She had single nucleotide polymorphism of p53.

 

Leon PM, Campos VF, Thurow HS, Hartwig FP, Selau LP, Dellagostin OA, Neto JB, Deschamps JC, Seixas FK, Collares T. Association between single nucleotide polymorphisms in p53 and abortion in Thoroughbred mares. Vet J. 2012; 193: 573-575.

Cord abnormalities

Abnormal length

The length of the normal equine placenta is between 36 and 84cm. Elongated cords and cords that are too short are both potential causes of fetal loss or perinatal mortality.

Single umbilical artery

There should be 2 umbilical arteries.

Girodroux et al (2017) reported finding a single umbilical artery in a foal. The cord was too long but the single artery was not considered a cause of clinical issues.

Girodroux M, Lores M, Vilaregut L, Wilsher S. A single umbilical artery and omphalophlebitis in an Arabian foal. Equine Veterinary Education 2017:

Torsion of cord

 

Foote AK, Ricketts SW, Whitwell KE. A racing start in life? The hurdles of equine feto-placental pathology. Equine Vet J Suppl. 2012 Feb;(41):120-129.

Smith KC, Blunden AS, Whitwell KE, Dunn KA, Wales AD. A survey of equine abortion, stillbirth and neonatal death in the UK from 1988 to 1997. Equine Vet J. 2003l; 35: 496-501.

Whitwell KE, Jeffcott LB. Morphological studies on the fetal membranes of the normal singleton foal at term. Res Vet Sci. 1975; 19: 44-55.

Whitwell KE. Morphology and pathology of the equine umbilical cord. J Reprod Fertil Suppl. 1975; 23: 599-603.

Hydrallanois/hydramnios

These are the result of change in the fluid volume of the allantois and amnion. Little is known of their cause. Leptospirosis is a reported cause.

Mitchell et al (2019) reported on the succesful birth of a foal in a mare with hydrallantois.

 

Mitchell ARM, Delvescovo B, Tse M, Crouch EE, Cheong SH, Castillo JM, Felippe MJB, Ainsworth DM, de Amorim MD. Successful management of hydrallantois in a Standardbred mare at term resulting in the birth of a live foal. Can Vet J. 2019; 60: 495-501.

Processionary caterpillars/Mare Reproductive Loss Syndrome/Equine Amnionitis and fetal loss

Mare Reproductive Loss Syndrome of horses first reported in Kentucky and Equine Amnionitis and Fetal Loss in Australia are diseases related to ingestion of processionary caterpillars. The association of abortion and these caterpillars was based on observational and epidemiological factors, and the lesions initially identified were infectious and inflammatory. It is now known that the setae of caterpillars penetrate the intestine and migrate laterally. If they penetrate the pregnant uterus, they cause failure of pregnancy by carrying environmental type bacteria into the uterus and conceptus to cause infection, including endometritis, chorioallantoic placentitis and amnionitis and funiculitis.

 

Todhunter KH, Cawdell-Smith AJ, Bryden WL, Perkins NR, Begg AP. Processionary caterpillar setae and equine fetal loss: 1. Histopathology of experimentally exposed pregnant mares. Vet Pathol 2014; 51: 1117-1130.

Todhunter KH, Cawdell-Smith AJ, Bryden WL, Perkins NR, Begg AP. Processionary caterpillar setae and equine fetal loss: 2. Histopathology of the fetal-placental unit from experimentally exposed mares. Vet Pathol 2014; 51: 1131-1142.

 

 

Mycotoxicosis

Fescue endophyte toxicosis Neotyphodium coenophialum

Pregnant mares who ingest Paspalum infected with Claviceps purpurea and Festuca elatior (tall fescue) infected with the endophyte Neotyphodium coenophialum. The seed head contains the most indole-diterpenoid mycotoxins.

 

 

Riet-Correa F, Rivero R, Odriozola E, Adrien Mde L, Medeiros RM, Schild AL. Mycotoxicoses of ruminants and horses. J Vet Diagn Invest. 2013 Nov;25(6):692-708.

Twinning

The dogma that there is a limited amount of exchange area of the equine uterus and that slight reduction in surface area will result in failure of pregnancy is typified by the rareity of live birth of twin foals. Anaya et al (2018) reported on Spanish horses where 23 twin pregnancies resulted in live foals out of 21,097 (0.066% prevalence). There were 23 live births.

 

Anaya G, Fernández ME, Valera M, Molina A, Azconab F, Azorc P, Soléc M, Moreno-Millán M, Demyda-Peyrás D. Prevalence of twin foaling and blood chimaerism in purebred Spanish horses. The Vet J 2018; 234: 142-144


Infectious

General reviews

Canisso et al (2015) provide a comprehensive review of placentitis.


Canisso I, Barry A. Ball BA, Erol E, Squires EL, Troedsson M. Comprehensive Review on Equine Placentitis. AAEP Proceedings 2015; 61: 490-509

 

Bacteria

Bacterial placentitis has several different pathogenesies. One very common mode is by transcervical infection of the placenta - ascending infection. To reach the placenta, bacteria from the vagina must pass the cervical barrier. This barrier is partly physical (the cervical epithelium and stroma, and the cervical mucus plug.

 

Loux SC, Scoggin KE, Troedsson MH, Squires EL, Ball BA. Characterization of the cervical mucus plug in mares. Reproduction. 2017; 153: 197-210.

Actinobacillus spp

Family Pasteurellaceae; Actinobacillus equuli subsp equuli and subsp haemolyticus

Bacteria of the genus Actinobacillus are normal inhabitants of the alimentary and reproductive tract of horses. They can cause septicemia and reproductive disease (endometritis and failure of pregnancy). They are often recovered with Streptococcus equi subsp zooepidemicus.

 

 

Layman QD, Rezabek GB, Ramachandran A, Love BC, Confer AW. A retrospective study of equine actinobacillosis cases: 1999-2011. J Vet Diagn Invest. 2014; 26: 365-375.

 

Streptococcus equi subsp. zooepidemicus

A common bacteria found in ascending placentitis in mares is Streptococcus equi subsp. zooepidemicus.

Fedorka et al (2019) inoculated mares with this bacterium in the cervix and measured cytokines in maternal and fetal circulation (no effect was detected), in the amniotic fluid (changes identified) and allantoic fluid (no change), but the chorioallantois and endometrium had a proinflammatory response. Fetal organs (liver and spleen) had an immunomodulating change.

 

Fedorka CE, Ball BA, Scoggin KE, Loux SC, Troedsson MHT, Adams AA. The feto-maternal immune response to equine placentitis. Am J Reprod Immunol. 2019; 82: e13179

Leptospira interrogans

Abortion due to Leptospira interrogans represents up to 13% of Failure of Pregancy in mares in some locales. Leptospira interrogans serovar Pomona is probably the most common isolate. In Kentucky, the common serovar is Leptospira interrogans serovar Pomona type kennewicki and about 6% of FOPs are leptospira related based on PCR testing and serology for serovar determination.

Foals infected in late gestation with Leptospires usually abort or are stillborn, but weak foals with icterus, hepatomegaly and petechia can be found. Leptospires may be found in the placenta, umbilical cord, kidney, and liver. Placentitis with oedema and areas of necrosis in the Hydrallantois occasionally develops. The fetal liver may be swollen, have yellow discoloration. Microscopic lesions include multifocal necrosis and lymphocytes and plasma cells may be in the portal triads. Some have giant cells. Other lesions include interstitial nephritis, pulmonary haemorrhage, myocarditis and meningitis. Funisitis with diffuse yellowish discoloration of the umbilical cord may be seen also.

 

Erol E, Jackson CB, Steinman M, Meares K, Donahoe J, Kelly N, Locke S, Smith JL, Carter CN. A diagnostic evaluation of real-time PCR, fluorescent antibody and microscopic agglutination tests in cases of equine leptospiral abortion. Equine Vet J. 2015; 47: 171-174.

Divers TJ, Chang YF, Irby NL, Smith JL, Carter CN. Leptospirosis: An important infectious disease in North American horses. Equine Vet J. 2019; 51: 287-292.

 

Nocardioform actinomycete organisms of nocardioform placentitis

There are numerous species of nocardioform bacteria cultured from nocardioform placentitis including Amycolatopsis kentuckyensis, Amycolatopsis lexingtonensis Amycolatopsis pretoriensis and Crossiela equi. Streptomyces atriruber and Streptomyces silaceus have also been isolated from cases of nocardioform placentitis.

It is not known how the infection occurs and attempts to reproduce the disease were unsuccessful.

Lesions occur in an unusual location. Rather than being at the cervical star, they tend to be a distinct region of thick light brown tenacious exudate on the chorion at the bifurcation of the horns on the lateral and ventral surface of the placenta.

 

Canisso IF, Ball BA, Erol E, Claes A, Scoggin KE, McDowell KJ, Williams NM, Dorton AR, Wolfsdorf KE, Squires EL, Troedsson MH. Attempts to induce nocardioform placentitis (Crossiela equi) experimentally in mares. Equine Vet J. 2015; 47: 91-95.

Mycobacteria

Mycobacterial failure of pregnancy is very rare. There are several single case reports

 

Johnson et al (2012) reported on a case of abortion due to Mycobacterium runyon group IV. There was brown discolouration of the amnion and allantois, and marked edema. Bacilli were in trophoblasts but there was little inflammation.

 

 

Johnson AK, Roberts JF, Hagan A, Wilborn RR, Dujovne G, Sells SF, Donahue JM. Infection of an equine placenta with a novel mycobacterial species leading to abortion. J Vet Diagn Invest. 2012; 24: 785-790.

Chlamydia psittaci

Chlamydia psittaci is not a widely recognised cause of failure of pregnancy in horses. It fits in the 'possible' and 'occasional' group.

Szeredi et al (2005) reported finding Chlamydia psittaci in the trophoblasts of mares who had aborted. They identified Chlamydia psittaci in 64 of 77 cases of abortion and considered it the cause in 11 cases.

Taylor et al (2017) found Chlamydia psittaci by PCR in 37 of 184 'equine reproductive loss events". Nothing further was reported. There was no evidence of transmission to humans.

Jelocnik et al (2018) provided evidence of the a dove origin Chlamydia psittaci as a cause of abortion in horses.

Akter et al (2020) reported on 2 cases of abortion (and one weak foal) that had PCR positive lung and placenta. Histological lesions were not reported as they did not have fixed tissue.

 

 

Akter R, Stent AW, Sansom FM, Gilkerson JR, Burden C, Devlin JM, Legione AR, El-Hage CM. Chlamydia psittaci: a suspected cause of reproductive loss in three Victorian horses. Aust Vet J. 2020; 98: 570-573.

Bocklisch H, Ludwig C, Lange S. Chlamydia as the cause of abortions in horses. Berl Munch Tierarztl Wochenschr. 1991; 104: 119-124.

Borel N, Polkinghorne A, Pospischil A. A Review on Chlamydial Diseases in Animals: Still a Challenge for Pathologists? Vet Pathol. 2018; 55: 374-390

Forster JL, Wittenbrink MM, Häni HJ, Corboz L, Pospischil A. Absence of Chlamydia as an aetiological factor in aborting mares. Vet Rec. 1997; 141: 424.

Glávits R, Molnár T, Rády M. Chlamydia-induced abortion in a horse. Acta Vet Hung. 1988; 36: 33-36.

Jelocnik M, Jenkins C, O'Rourke B, Barnwell J, Polkinghorne A. Molecular evidence to suggest pigeon-type Chlamydia psittaci in association with an equine foal loss. Transbound Emerg Dis. 2018; 65: 911-915.

Szeredi L, Hotzel H, Sachse K. High prevalence of chlamydial (Chlamydophila psittaci) infection in fetal membranes of aborted equine fetuses. Vet Res Commun. 2005 Mar;29 Suppl 1:37-49.

Taylor KA, Durrheim D, Heller J, O'Rourke B, Hope K, Merritt T, Freeman P, Chicken C, Carrick J, Branley J, Massey P. Equine chlamydiosis-An emerging infectious disease requiring a one health surveillance approach. Zoonoses Public Health. 2017

Coxiella burnetti

Neorickettsia ristici

Phylum: Proteobacteria, Class Alphaproteobacteria; Order Rickettsiales, Family Anaplasmataceae, Genus Neorickettsia, Species Neorickettsia ristici

Neorickettsia ristici is the causative agent of Potomic horse fever or Equine monocytic ehrlichiosis.

 

 

Fungi

Geotrichum candidum

 

Protozoa

Neospora caninum

Neospora caninum is a common abortogenic agent of cattle. Little is known of the importance in horses. Serology for Neospora caninum, which cross reacts with Neospora hughesi, has been done in horses. About 20% of 296 slaughtered horses in Wyoming had a positive serum titre.

Dubey and Porterfield reported on a case of equine abortion due to Neospora sp.Only lung was examined histologically and tachyzoites were visible there.

 

Duby JP, Porterfield ML. Neospora caninum (Apicomplexa) in an aborted equine fetus. J Parasit 1990; 76: 732-734

Dubey JP, Romand S, Thulliez P, Kwok OC, Shen SK, Gamble HR. Prevalence of antibodies to Neospora caninum in horses in North America. J Parasitol. 1999; 85: 968-969.

 

Neospora hughesi

Anderson et al (2019) reported on a confirmed case at 280 days gestation. Lesions were in the lungs, liver and heart.

Anderson JA, Alves DA, Cerqueira-Cézar CK, da Silva AF, Murata FHA, Norris JK, Howe DK, Dubey JP. Histologically, immunohistochemically, ultrastructurally, and molecularly confirmed neosporosis abortion in an aborted equine fetus. Vet Parasitol. 2019; 270: 20-24.

 

 

Viruses

Equid alphaherpesvirus 1

The most common cause of viral abortion and therefore of herpesviral failure of pregnancy is Equid alphaherpesvirus I aka equine herpesvirus 1 (EHV-1). EHV-1 is in the family Herpesviridae, subfamily Alphaherpesvirinae, genus Varicellovirus.

 

A horse is usually infected through the respiratory mucosa from whence virus spreads to the local lymphoid tissue and then spreads within lymphocytes throughout the body. Viraemia lasts about 14 days and subsequently target tissues are infected. Within the uterus, endothelial cells of arterioles in the pregnant uterus are infected. Small infarcts occur and it is through these that virus enters the fetus to produce a fetal viraemia. Failure of pregnancy is from the effects on endothelial cells in the pregnant uterus and fetal disease.

Latent infection in lymphoid tissues and trigeminal ganglia occurs. Triggers for recrudescence are largely unknown.

Any strain of EHV-1 can cause abortion, even the neuropathogenic strain.

 

Lunn DP1, Davis-Poynter N, Flaminio MJ, Horohov DW, Osterrieder K, Pusterla N, Townsend HG. Equine herpesvirus-1 consensus statement. J Vet Intern Med. 2009; 23: 450-461.

Marenzoni ML1, Bietta A, Lepri E, Casagrande Proietti P, Cordioli P, Canelli E, Stefanetti V, Coletti M, Timoney PJ, Passamonti F. (2013) Role of equine herpesviruses as co-infecting agents in cases of abortion, placental disease and neonatal foal mortality. Vet Res Commun (2013) 37: 311–317.

Smith KC, Borchers K. (2001) A study of the pathogenesis of equid herpesvirus-1 (EHV-1) abortion by DNA in-situ hybridization. J Comp Pathol 2001; 125: 304-310.

Alphaarterivirus equid (equine arteritis virus [EAV])

EAV is of the Order Nidovirales, Family Arteriviridae, Genus Arterivirus. It produces a variety of clinical effects in adults but in mares, infertility, early embryonic mortality, abortion and stillbirth.

Most pregnant mares abort fetuses without fetal or placental lesions. The virus infects smooth muscle cells of the myometrium and induces necrotic myometritis.

Some fetuses become viremic and have fibrinoid vasculitis, interstitial pneumonia, and renal tubular necrosis.

Many stallions become inapparent clinical carriers of the virus after the acute phase. Spread to mares is venereal or directly horizontal.

Mares clear the virus quickly but stallions develop persistent infection of the testis.

 


Placental disease

Placentitis

Serum amyloid A concentration in mares with placentitis is above normal and higher in those that abort than those that do not abort. Levels return to normal after parturition. This could be used as a prognostic tool in mares diagnosed with placentitis.

 

Coutinho da Silva MA, Canisso IF, MacPherson ML, Johnson AEM, Divers TJ(2013) Serum amyloid A concentration in healthy periparturient mares and mares with ascending placentitis (pages 619–624). Equine Vet J 2013; 45: 619-624.

 

Processionary caterpillars

 

Cawdell-Smith AJ, Todhunter KH, Perkins NR, Bryden WL (2013) Exposure of mares to processionary caterpillars (Ochrogaster lunifer) in early pregnancy: An additional dimension to equine amnionitis and fetal loss. Equine Vet J 2013; 45: 755–760


Neoplasia

Hepatoblastoma

 

deVries et al (2013) reported on a foal that died with peritoneal metastases from a hepatoblastoma.

de Vries C, Vanhaesebrouck E, Govaere J, Hoogewijs M, Bosseler L, Chiers K, Ducatelle R. Congenital ascites due to hepatoblastoma with extensive peritoneal implantation metastases in a premature equine fetus. J Comp Pathol 2013; 148: 214-219.

Placental mixed germ cell tumor

Brockenstedt et al (2015) reported a case of equine placental mixed germ cell tumor with supposed metastasis to the liver of a foal. Metastasis occurred and the foal was euthanised at 52 days of age

Bockenstedt MM, Fales-Williams A, Haynes JS. Equine placental mixed germ cell tumor with metastasis to the foal. Vet Pathol 2015; 52: 360-363.

Teratoma

Is exceedingly rare for teratoma to be found in the placenta or the foal enutero.

Gurfield and Benirschke (2003) reported a case of placental teratoma in a fetal foal.

Binanti et al (2013) reported on a case where a teratoma was attached to the umbilical cord. It was 20 x 30 x 20 cm no description of the exact location on the umbilical cord was provided.From the photograph it appears to be close to the umbilicus of the foal.

 

 

Binanti D, Livini M, Riccaboni P, Sironi G. A case of umbilical cord teratoma in an aborted foal. J Vet Diagn Invest. 2013; 25: 173-175.

Gurfield N, Benirschke K. Equine placental teratoma. Vet Pathol. 2003 Sep;40(5):586-8.