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Topic:Vascular

The vascular system in horses encompasses a network of blood vessels responsible for the circulation of blood throughout the body. This system includes arteries, veins, and capillaries, which facilitate the transport of oxygen, nutrients, and waste products to and from tissues. The vascular health of horses is vital for maintaining overall physiological function and performance. Common areas of study within equine vascular research include the examination of blood flow dynamics, vascular diseases, and the impact of exercise on vascular function. This page compiles peer-reviewed research studies and scholarly articles that explore the structure, function, and clinical relevance of the vascular system in equine health.
Changes in maternal pregnane concentrations in mares with experimentally-induced, ascending placentitis.
Theriogenology    September 7, 2018   Volume 122 130-136 doi: 10.1016/j.theriogenology.2018.09.001
Wynn MAA, Ball BA, May J, Esteller-Vico A, Canisso I, Squires E, Troedsson M.The objectives of this study were to compare via liquid chromatography-tandem mass spectrometry (LC-MS/MS) progesterone (P4), 5α-dihydroprogesterone (DHP), allopregnanolone, 3β-hydroxy-5α-pregnan-20-one (3β5P), 20α-hydroxy-5α-pregnan-3-one (20α5P), 5α-pregnan-3β,20α-diol (βα-diol), and 5α-pregnan-3β,20β-diol (ββ-diol) concentrations in plasma of mares with experimentally-induced, ascending placentitis compared to gestationally age-matched control mares. Placentitis was induced via intracervical inoculation of Streptococcus equi spp. zooepidemicus between 260 and 280 days of ge...
Gene Therapy Using Plasmid DNA Encoding VEGF164 and FGF2 Genes: A Novel Treatment of Naturally Occurring Tendinitis and Desmitis in Horses.
Frontiers in pharmacology    August 31, 2018   Volume 9 978 doi: 10.3389/fphar.2018.00978
Kovac M, Litvin YA, Aliev RO, Zakirova EY, Rutland CS, Kiyasov AP, Rizvanov AA.This clinical study describes the intralesional application of the plasmid DNA encoding two therapeutic species-specific growth factors: vascular endothelial growth factor (VEGF164) and fibroblast growth factor 2 (FGF2) in seven horses to restore naturally occurring injuries of the superficial digital flexor tendon (SDFT) (tendinitis) and in three horses with suspensory ligament branch desmitis. Following application all horses were able to commence a more rapid exercise program in comparison to standardized exercise programs. Clinical observation and ultrasonic imaging was used to evaluate th...
Detection and genotyping of equid herpesvirus 1 in Uruguay.
Revue scientifique et technique (International Office of Epizootics)    August 31, 2018   Volume 36, Issue 3 799-806 doi: 10.20506/rst.36.3.2715
Castro ER, Arbiza J.Infection with equid alphaherpesvirus 1 (EHV-1) causes respiratory disease, abortion and neurological disorders in horses. Molecular epidemiology studies have demonstrated that a single nucleotide polymorphism (A2254/G2254) in the genome region of open reading frame 30 which results in an amino acid variation (N752/D752) of the EHV-1 DNA polymerase, is significantly associated with the neuropathogenic potential of naturally occurring strains. In recent years, an increase in the number of cases of equine neurological disease caused by neuropathogenic variants of EHV-1 has been observed in numer...
Equine pericardium-covered stenting in post-traumatic pseudoaneurysm of cavernous internal carotid artery.
Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences    July 5, 2018   Volume 24, Issue 6 635-638 doi: 10.1177/1591019918785150
Gonzalez-Cantero JL, Del Valle Diéguez M, Monteserín Matesanz C, Saura Lorente J, Villoria Medina F, Fortea Gil F, Castro Reyes E.We report a case of traumatic intracranial carotid artery pseudoaneurysm treated with an equine pericardium-covered stent. The patient was admitted to the Emergency Department after sustaining severe polytrauma in a motor vehicle accident. A cavernous carotid pseudoaneurysm was detected after an episode of massive epistaxis that required emergent nasal packing. Treatment with parent vessel sacrifice was ruled out after an unfavourable balloon test occlusion. We opted for an equine pericardium-covered stent as a means to immediately seal the wall defect in the setting of massive bleeding second...
Treatment of limb wounds of horses with orf virus IL-10 and VEGF-E accelerates resolution of exuberant granulation tissue, but does not prevent its development.
PloS one    May 15, 2018   Volume 13, Issue 5 e0197223 doi: 10.1371/journal.pone.0197223
Wise LM, Bodaan CJ, Stuart GS, Real NC, Lateef Z, Mercer AA, Riley CB, Theoret CL.Bandaging of limb wounds in horses leads to formation of exuberant granulation tissue (EGT) that retards healing due to protracted inflammation, aberrant vascularisation and delayed epithelialisation. EGT is not observed if wounds are left undressed or when wounds are on the body. A previous study showed that short-term administration of proteins derived from orf virus dampened inflammation and promoted epithelialisation of open wounds in horses. Here, we investigated the impact of orf virus interleukin-10 and vascular endothelial growth factor-E on the development and resolution of EGT. Excis...
Combined thickness of the uterus and placenta and ultrasonographic examinations of uteroplacental tissues in normal pregnancy, placentitis, and abnormal parturitions in heavy draft horses.
Journal of equine science    March 23, 2018   Volume 29, Issue 1 1-8 doi: 10.1294/jes.29.1
Kimura Y, Haneda S, Aoki T, Furuoka H, Miki W, Fukumoto N, Matsui M, Nambo Y.The combined thickness of the uterus and placenta (CTUP) and ultrasonographic images of uteroplacental tissues were investigated in 35 pregnant heavy draft horses in Months 7-12 of pregnancy. The mares were divided into three groups: those pathologically diagnosed as placentitis (placentitis group, n=3); those who had abortion, premature birth, or fetal malformation (abnormal group, n=7); and those who had no abnormal findings (normal group, n=25). In the normal group, CTUP increased as pregnancy progressed from Months 7 (median, 7.08 mm; range, 5.68-11.27) to 12 (13.31 mm; 7.44-16.31 mm) (P<0...
[Influence of Venous Catheters on Jugular Vein Diseases in Horses].
Tierarztliche Praxis. Ausgabe G, Grosstiere/Nutztiere    March 23, 2018   Volume 46, Issue 1 60-61 doi: 10.1055/s-0038-1638245
Treupel E.No Abstract available
[Causes of abortion in horses – overview of the literature and own evaluations].
Tierarztliche Praxis. Ausgabe G, Grosstiere/Nutztiere    February 21, 2018   Volume 46, Issue 1 35-42 doi: 10.15653/TPG-170517
Weber R, Hospes R, Wehrend A.The aim of this study was to summarize the current status of the possible causes, clinical symptoms and pathogenesis of abortion in the mare and to evaluate the frequency of varying causes of abortion in German thoroughbred breeding. An analysis of the literature using electronic libraries, journals and textbooks was performed. In addition, the results of examinations of 123 abortions of thoroughbred breeding in central Germany were evaluated. In the literature, bacterial infections are the most frequently described cause of abortion. Other important causes are infections with equine herpesvir...
Genetic diversity of equine herpesvirus 1 isolated from neurological, abortigenic and respiratory disease outbreaks.
Transboundary and emerging diseases    February 9, 2018   Volume 65, Issue 3 817-832 doi: 10.1111/tbed.12809
Bryant NA, Wilkie GS, Russell CA, Compston L, Grafham D, Clissold L, McLay K, Medcalf L, Newton R, Davison AJ, Elton DM.Equine herpesvirus 1 (EHV-1) causes respiratory disease, abortion, neonatal death and neurological disease in equines and is endemic in most countries. The viral factors that influence EHV-1 disease severity are poorly understood, and this has hampered vaccine development. However, the N752D substitution in the viral DNA polymerase catalytic subunit has been shown statistically to be associated with neurological disease. This has given rise to the term "neuropathic strain," even though strains lacking the polymorphism have been recovered from cases of neurological disease. To broaden understan...
Equid herpesvirus 8: Complete genome sequence and association with abortion in mares.
PloS one    February 7, 2018   Volume 13, Issue 2 e0192301 doi: 10.1371/journal.pone.0192301
Garvey M, Suárez NM, Kerr K, Hector R, Moloney-Quinn L, Arkins S, Davison AJ, Cullinane A.Equid herpesvirus 8 (EHV-8), formerly known as asinine herpesvirus 3, is an alphaherpesvirus that is closely related to equid herpesviruses 1 and 9 (EHV-1 and EHV-9). The pathogenesis of EHV-8 is relatively little studied and to date has only been associated with respiratory disease in donkeys in Australia and horses in China. A single EHV-8 genome sequence has been generated for strain Wh in China, but is apparently incomplete and contains frameshifts in two genes. In this study, the complete genome sequences of four EHV-8 strains isolated in Ireland between 2003 and 2015 were determined by I...
Molecular evidence to suggest pigeon-type Chlamydia psittaci in association with an equine foal loss.
Transboundary and emerging diseases    January 19, 2018   Volume 65, Issue 3 911-915 doi: 10.1111/tbed.12817
Jelocnik M, Jenkins C, O'Rourke B, Barnwell J, Polkinghorne A.Chlamydia psittaci is an important avian pathogen with spillover from infected wild and domesticated birds also posing a risk to human health. We recently reported a case of C. psittaci equine placentitis associated with further spillover to humans. Molecular typing of this case revealed it belonged to the 6BC clade of C. psittaci, a globally distributed highly virulent set of strains, typically linked to infection spillover from parrots. Equine chlamydiosis associated with C. psittaci infection has previously been reported elsewhere in countries where parrots are not endemic, however, rais...
Patterns of conceptus development and of progesterone concentrations in maternal blood preceding spontaneous early pregnancy failure in mares.
Reproduction, fertility, and development    January 9, 2018   Volume 30, Issue 8 1066-1076 doi: 10.1071/RD17336
Betteridge KJ, Raeside JI, Waelchli RO, Christie HL, Hayes MA.Sixteen cases of spontaneous pregnancy loss (11 of singletons and five of pairs of twins) are described. The losses occurred between gestation Days 13 and 25 in 12 mares being monitored almost daily by transrectal ultrasonography (for measurement of conceptus growth) and blood sampling (for determination of maternal plasma progesterone concentrations as evidence of luteolysis) in experimental studies of early pregnancy. In 10 of the 16 cases the uterus was flushed and eight conceptuses were recovered for morphological assessment. Five of the 11 losses of singletons occurred before Day 16 and, ...
Comparative Genomic Sequencing and Pathogenic Properties of Equine Herpesvirus 1 KyA and RacL11.
Frontiers in veterinary science    December 11, 2017   Volume 4 211 doi: 10.3389/fvets.2017.00211
Shakya AK, O'Callaghan DJ, Kim SK.Equine herpesvirus 1 (EHV-1) is a major pathogen affecting equines worldwide. The virus causes respiratory disease, abortion, and, in some cases, neurological disease. EHV-1 Kentucky A (KyA) is attenuated in the mouse and equine, whereas wild-type pathogenic strain RacL11 induces severe inflammatory infiltration of the lung, causing infected mice to succumb. The complete DNA sequencing of the KyA genome revealed that genes UL17 (ORF17), US6 (ORF73; gI), US7 (ORF74; gE), and US8 (ORF75; 10 K) are deleted as compared to the RacL11 and Ab4 genomes. In-frame deletions in the US1 (ORF68), US4 (OR...
Reproductive effects of arteriviruses: equine arteritis virus and porcine reproductive and respiratory syndrome virus infections.
Current opinion in virology    November 21, 2017   Volume 27 57-70 doi: 10.1016/j.coviro.2017.11.005
Balasuriya UB, Carossino M.Equine arteritis virus (EAV) and porcine reproductive and respiratory syndrome virus (PRRSV) are the most economically important members of the family Arteriviridae. EAV and PRRSV cause reproductive and respiratory disease in equids and swine, respectively and constitute a significant economic burden to equine and swine industries around the world. Furthermore, they both cause abortion in pregnant animals and establish persistent infection in their natural hosts, which fosters viral shedding in semen leading to sexual transmission. The primary focus of this article is to provide an update on t...
Aborted fetal sizes of Thoroughbred horses in Hidaka, Japan, between 2005 and 2015.
Journal of equine science    July 6, 2017   Volume 28, Issue 2 47-53 doi: 10.1294/jes.28.47
Murase H, Miyazawa M, Harada T, Ozawa M, Sato F, Hada T.The degree of fetal growth restriction has been unclear in equine reproduction. In this study, 2,195 fetuses from 2,137 abortions during 11 seasons were examined to determine the causes of abortion, and fetal size dimensions (crown rump length and body weight) were measured. In total, 900 cases (42.1%) of abortion were identified as caused by viral infection (215, 10.1%), bacterial infection (156, 7.3%), fungal infection (25, 1.2%), circulation failure (406, 19.0%), multiple causes (66, 3.1%), deformity (13, 0.6%), placental abnormality (12, 0.6%), and other causes (7, 0.3%). All viral infecti...
Genetic characterization of equid herpesvirus type 1 from cases of abortion in Poland.
Archives of virology    April 27, 2017   Volume 162, Issue 8 2329-2335 doi: 10.1007/s00705-017-3376-3
Stasiak K, Dunowska M, Hills SF, Rola J.Equid herpesvirus type 1 (EHV-1) is a common viral infection associated with varied clinical outcomes including respiratory disease, abortion and neurological disease. We have characterized EHV-1 sequences (n = 38) obtained from cases of equine abortion in Poland between 1999 and 2016, based on sequencing of PCR products from open reading frames (ORF) 30 and 68 of the EHV-1 genome. The majority (81.6%) of sequences were not classified into any of the previously described groups based on the ORF68 sequence. The remaining sequences belonged to ORF68 group III (7.9%) or IV (10.5%). A haplotype ne...
Follicular dynamics, ovarian vascularity and luteal development in mares with early or late postpartum ovulation.
Theriogenology    March 27, 2017   Volume 96 23-30 doi: 10.1016/j.theriogenology.2017.03.020
Lemes KM, Silva LA, Alonso MA, Celeghini ECC, Pugliesi G, Carvalho HF, Affonso FJ, Silva DF, Leite TG, de Arruda RP.Follicular development and deviation processes during the postpartum period are not completely known in horses. Thus, we aimed to study the characteristics of follicular dynamics and ovarian vascular perfusion during the postpartum period in mares that demonstrated estrous behavior and had early ( 0.1) was detected between the groups when the data were normalized for the days preceding the first postpartum ovulation (from D-7 to D-1). However, when the data were normalized to days postpartum, the dominant follicle was larger (P 25 mm diameter was greater (P  0.1) was detected between grou...
Bilateral oblique facial clefts, rudimentary eyes and hydrocephalus in an aborted equine foetus.
Reproduction in domestic animals = Zuchthygiene    March 22, 2017   Volume 52, Issue 4 692-695 doi: 10.1111/rda.12962
Agerholm JS, Pedersen HG, McEvoy FJ, Heegaard S.Knowledge of congenital malformations and their causes in horses is generally sparse. Such conditions require more scientific attention to improve their diagnostics and inform prevention strategies. Here, a unique syndrome of bilateral oblique facial clefts (meloschisis), rudimentary eyes and hydrocephalus is reported in an equine foetus spontaneously aborted at gestation day 224. The cause of abortion was considered to be intrauterine death caused by umbilical cord torsions and subsequent compromised blood flow, but the aetiology of the malformation could not be determined. A detailed history...
Theileria equi infection causing abortion in a mare in Brazil.
Veterinary parasitology, regional studies and reports    March 20, 2017   Volume 8 113-116 doi: 10.1016/j.vprsr.2017.03.008
de Sousa SH, Paludo GR, Freschi CR, Machado RZ, de Castro MB.The aim of this report was to confirm the cause of abortion to be Theileria equi acquired transplacentally in a mare in Federal District, Brazil. The aborted fetus showed a high parasitemia of erythrocytes (80%) by the oval and Maltese cross forms of T. equi. Necropsy of the fetus demonstrated congestion of organs, jaundice, anemia and pronounced spleno- and hepatomegaly. Twelve breeding mares, including the one that aborted and her fetus, tested positive for T. equi infection by universal and multiplex PCR assay. The absence of histopathologic changes such as inflammation and necrosis in the ...
Systemic and intrafollicular components of follicle selection in mares.
Domestic animal endocrinology    December 22, 2016   Volume 59 116-133 doi: 10.1016/j.domaniend.2016.12.005
Ginther OJ.Mares are superb models for study of follicle selection owing to similarities between mares and women in relative follicle diameters at specific events during the follicular wave and follicle accessibility for experimental sampling and manipulation. Usually, only 1 major follicular wave with a dominant follicle (DF) greater than 30 mm develops during the 22 to 24 d of the equine estrous cycle and is termed the primary or ovulatory wave. A major secondary wave occasionally (25%) develops early in the cycle. Follicles of the primary wave emerge at 6 mm on day 10 or 11 (day 0 = ovulation). The...
Equine disease surveillance: quarterly summary.
The Veterinary record    October 30, 2016   Volume 179, Issue 17 428-431 doi: 10.1136/vr.i5679
of surveillance testing, April to June 2016Continuing reports of abortion due to equine herpesvirus type 1 infectionInternational disease occurrence in the second quarter of 2016These are among matters discussed in the most recent quarterly equine disease surveillance report, prepared by Defra, the Animal Health Trust and the British Equine Veterinary Association.
Genetic characterization of equine herpesvirus 1 isolates from abortion outbreaks in India.
Archives of virology    October 3, 2016   Volume 162, Issue 1 157-163 doi: 10.1007/s00705-016-3097-z
Anagha G, Gulati BR, Riyesh T, Virmani N.Equine herpesvirus 1 (EHV1) is a common pathogen of horses that causes upper respiratory tract disease, abortion, neonatal death and neurological disease. The neurological form of disease is called equine herpesvirus myeloencephalopathy (EHM). During the past decade, the incidence of EHM has been on the rise in Europe, North America, Australia and Asia. Some EHV1 isolates causing EHM exhibit a single-nucleotide polymorphism (SNP) in the DNA polymerase gene (ORF30) at position 2254 (A to G). Further, based on polymorphism in the ORF68, EHV1 isolates have been classified into different groups. T...
Vascular Dysfunction in Horses with Endocrinopathic Laminitis.
PloS one    September 29, 2016   Volume 11, Issue 9 e0163815 doi: 10.1371/journal.pone.0163815
Morgan RA, Keen JA, Walker BR, Hadoke PW.Endocrinopathic laminitis (EL) is a vascular condition of the equine hoof resulting in severe lameness with both welfare and economic implications. EL occurs in association with equine metabolic syndrome and equine Cushing's disease. Vascular dysfunction, most commonly due to endothelial dysfunction, is associated with cardiovascular risk in people with metabolic syndrome and Cushing's syndrome. We tested the hypothesis that horses with EL have vascular, specifically endothelial, dysfunction. Healthy horses (n = 6) and horses with EL (n = 6) destined for euthanasia were recruited. We studied v...
Orf virus interleukin-10 and vascular endothelial growth factor-E modulate gene expression in cultured equine dermal fibroblasts.
Veterinary dermatology    August 22, 2016   Volume 27, Issue 5 434-e114 doi: 10.1111/vde.12370
Wise LM, Bodaan CJ, Mercer AA, Riley CB, Theoret CL.Wounds in horses often exhibit sustained inflammation and inefficient vascularization, leading to excessive fibrosis and clinical complications such as "proud flesh". Orf virus-derived proteins, vascular endothelial growth factor (VEGF)-E and interleukin (ovIL)-10, enhance angiogenesis and control inflammation and fibrosis in skin wounds of laboratory animals. Objective: The study aimed to determine if equine dermal cells respond to VEGF-E and ovIL-10. Equine dermal cells are expected to express VEGF and IL-10 receptors, so viral protein treatment is likely to alter cellular gene expression an...
Detection of equine arteritis virus by two chromogenic RNA in situ hybridization assays (conventional and RNAscope(®)) and assessment of their performance in tissues from aborted equine fetuses.
Archives of virology    August 19, 2016   Volume 161, Issue 11 3125-3136 doi: 10.1007/s00705-016-3014-5
Carossino M, Loynachan AT, James MacLachlan N, Drew C, Shuck KM, Timoney PJ, Del Piero F, Balasuriya UB.Equine arteritis virus (EAV) is the causative agent of equine viral arteritis, a respiratory and reproductive disease of equids. EAV infection can induce abortion in pregnant mares, fulminant bronchointerstitial pneumonia in foals, and persistent infection in stallions. Here, we developed two RNA in situ hybridization (ISH) assays (conventional and RNAscope(®) ISH) for the detection of viral RNA in formalin-fixed paraffin-embedded (FFPE) tissues and evaluated and compared their performance with nucleocapsid-specific immunohistochemistry (IHC) and virus isolation (VI; gold standard) techniques...
Placental abnormalities in equine pregnancies generated by SCNT from one donor horse.
Theriogenology    May 26, 2016   Volume 86, Issue 6 1573-1582 doi: 10.1016/j.theriogenology.2016.05.017
Pozor MA, Sheppard B, Hinrichs K, Kelleman AA, Macpherson ML, Runcan E, Choi YH, Diaw M, Mathews PM.Placental changes associated with SCNT have been described in several species, but little information is available in this area in the horse. We evaluated the ultrasonographic, gross, and histopathological characteristics of placentas from three successful and five unsuccessful equine SCNT pregnancies, established using cells from a single donor horse. Starting at approximately 6-month gestation, the pregnancies were monitored periodically using transrectal (TR) and transabdominal (TA) ultrasonography (US) to examine the placentas, fetal fluids, and fetuses. Of the five mares that aborted, one...
Fatal Cowpox Virus Infection in an Aborted Foal.
Vector borne and zoonotic diseases (Larchmont, N.Y.)    May 9, 2016   Volume 16, Issue 6 431-433 doi: 10.1089/vbz.2015.1932
Franke A, Kershaw O, Jenckel M, König L, Beer M, Hoffmann B, Hoffmann D.The article describes the isolation of a cowpox virus (CPXV) isolate originating from a horse. The skin of a foal, aborted in the third trimester, displayed numerous cutaneous papules. The histological examination showed A-type inclusion bodies within the lesion, typical for CPXV infections. This suspicion was confirmed by real-time PCR where various organs were analyzed. From skin samples, virus isolation was successfully performed. Afterwards, the whole genome of this new isolate "CPXV Amadeus" was sequenced by next-generation technology. Phylogenetic analysis clearly showed that "CPXV Amade...
Polarisation of equine pregnancy outcome associated with a maternal MHC class I allele: Preliminary evidence.
Veterinary microbiology    April 6, 2016   Volume 188 34-40 doi: 10.1016/j.vetmic.2016.04.004
Kydd JH, Case R, Winton C, MacRae S, Sharp E, Ricketts SL, Rash N, Newton JR.Identification of risk factors which are associated with severe clinical signs can assist in the management of disease outbreaks and indicate future research areas. Pregnancy loss during late gestation in the mare compromises welfare, reduces fecundity and has financial implications for horse owners. This retrospective study focussed on the identification of risk factors associated with pregnancy loss among 46 Thoroughbred mares on a single British stud farm, with some but not all losses involving equid herpesvirus-1 (EHV-1) infection. In a sub-group of 30 mares, association between pregnancy ...
Elevated serum amyloid A levels in cases of aborted equine fetuses due to fetal and placental infections.
Theriogenology    March 24, 2016   Volume 86, Issue 4 971-975 doi: 10.1016/j.theriogenology.2016.03.021
Erol E, Jackson C, Horohov D, Locke S, Smith J, Carter C.Determination of fetal serum amyloid A (SAA) concentrations in aborted fetuses can provide valuable information regarding the infectious and/or inflammatory process of abortion in horses. To investigate the relationship between fetal SAA levels and the infectious/inflammatory disease process in feto-placental tissues, a SAA ELISA was used to test heart serum samples of 89 equine fetuses that were necropsied and diagnosed in the following groups: a multiorgan disease process diagnosed with an identified microorganism (14 cases, group 1); only placentitis diagnosed with an identified microorgan...
Abortions in Thoroughbred mares associated with consumption of bulbosus buttercups (Ranunculus bulbosus L).
Journal of the American Veterinary Medical Association    March 10, 2016   Volume 248, Issue 6 669-672 doi: 10.2460/javma.248.6.669
Swerczek TW.Unexplained clinical signs of weight loss and emaciation were reported in a herd of Thoroughbred horses grazing spring pastures on a central Kentucky farm, even though supplemental grain and hay were provided. Results: A buttercup plant, Ranunculus bulbosus L, was abundantly present in all pastures and paddocks on the farm. All horses, especially lactating mares and their foals, had mild to severe weight loss as assessed by body condition. Seven mares on the farm had been confirmed pregnant between 30 and 45 days of gestation, but were later found to have aborted. Two 2-year-old fillies develo...