Abstract: Ascending placentitis is a leading cause of late-term pregnancy loss in mares. Although pathogens are presumed to ascend from the caudal reproductive tract, the association between the vaginal microbiome and placentitis has not been systematically examined. Objective: To characterise microbial and host gene expression in the equine vagina during gestation and to identify taxa or transcripts that were associated with the presence of an abnormal placenta at birth. Methods: Prospective, paired observational study. Methods: Vaginal wall swabs were collected from 49 multiparous Thoroughbred mares at days 42-46 and 118-133 of gestation (first and second trimester). Pregnancies were monitored to term, and placentas were classified as normal (healthy) or abnormal. Complete data was available for 37 mares, and 13 were included in this study: normal (n = 6), abnormal (n = 5), and ascending placentitis (n = 2). Total RNA underwent deep dual RNA-sequencing. Alpha- and beta-diversity metrics, differential expression, and microbe-host correlation analyses were performed. Results: Global vaginal microbial diversity did not differ between mares with healthy or abnormal placentas. Several microbes from the phyla Actinomycetota and Pseudomonadota showed altered activity in mares with abnormal placentas. Vaginal transcriptome showed a subtle inflammatory response in the second trimester in the abnormal placenta group in the absence of clinical signs. Correlation analysis suggested an interaction between bacterial survival and virulence genes and host inflammation and apoptosis genes. Conclusions: Samples were obtained from clinical cases, limiting the availability of a complete history. Conclusions: Although overall vaginal microbial diversity was similar between outcome groups, distinct host vaginal transcriptional and microbial activity signatures distinguished mares with an abnormal placenta at birth. These findings warrant targeted investigation of the vaginal immune response and bacterial virulence factors as early biomarkers and therapeutic targets.
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Overview
This study investigated the relationship between vaginal microbes, host gene expression, and placental health in pregnant mares.
Researchers aimed to identify microbial and genetic signatures in the vagina that correlate with abnormal placentas or placentitis, a major cause of pregnancy loss.
Background and Objectives
Ascending placentitis causes late-term pregnancy loss by infection ascending from the reproductive tract.
There is limited understanding of how the vaginal microbiome and host gene expression relate to placental health in horses.
The objective was to characterize the vaginal microbiome and host gene expression during gestation and identify associations with abnormal placental outcomes.
Methods
Study design: Prospective, paired observational study involving multiparous Thoroughbred mares.
Sample collection: Vaginal wall swabs taken at two gestational timepoints – days 42-46 (first trimester) and days 118-133 (second trimester).
Data from 37 mares was available but 13 were selected for detailed RNA sequencing analysis based on placental outcome:
Normal placenta group (6 mares)
Abnormal placenta group (5 mares)
Ascending placentitis group (2 mares)
Techniques used:
Deep dual RNA-sequencing of total RNA to profile both microbial and host gene expression.
Statistical analyses including alpha- and beta-diversity of microbes, differential gene expression, and correlation analyses between microbial activity and host responses.
Key Findings
Microbial diversity:
No significant difference in overall vaginal microbial diversity between mares with healthy versus abnormal placentas.
Microbial activity:
Specific microbes from phyla Actinomycetota and Pseudomonadota showed altered gene activity associated with abnormal placentas.
Host vaginal transcriptome:
Subtle inflammatory gene expression changes observed in the second trimester in mares that later had abnormal placentas, even without clinical symptoms.
Correlation between host and microbes:
Interactions noted between bacterial genes related to survival and virulence and host genes involved in inflammation and apoptosis.
Conclusions and Implications
While the overall vaginal microbiome diversity was similar, distinct microbial and host gene expression signatures distinguish mares with abnormal placentas.
The findings suggest that early changes in vaginal bacteria and host immune responses are linked to placental health.
This highlights potential early biomarkers for placentitis and targets for therapeutic intervention to prevent pregnancy loss.
Limitations include the small sample size and limited clinical history from natural cases, underlining the need for further targeted research.
Cite This Article
APA
van Heule M, Heil B, Norris JK, Gedye K, Lin X, De Spiegelaere W, Daels P, Dini P.
(2026).
Vaginal host-microbe signatures linked to placental outcomes in mares.
Equine Vet J.
https://doi.org/10.1002/evj.70185
Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Heil, Babiche
Matamata Veterinary Services Equine, Matamata, New Zealand.
Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
Norris, Jamie K
Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
Gedye, Kristene
School of Veterinary Science-Tāwharau Ora, Massey University, Palmerston North, New Zealand.
Lin, Xiaoxiao
Massey Genome Service, Massey University, Palmerston North, New Zealand.
De Spiegelaere, Ward
Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Daels, Peter
Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Dini, Pouya
Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
Grant Funding
Special Research Fund at the University of Ghent (BOF)
New Zealand Equine Research Foundation
John P. Hughes Endowment
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