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Proteomics. Clinical applications2025; e202400095; doi: 10.1002/prca.202400095

Systemic Changes in Early Pregnancy in the Mare: An Integrated Proteomic Analysis of Blood Plasma, Histotroph, and Yolk Sac Fluid at Day 14 Post-Ovulation.

Abstract: Embryo-maternal signaling during the establishment of pregnancy in horses remains one of the biggest mysteries in large animal physiology. Early pregnancy loss represents a major source of economic loss to the breeding industry. This study aimed to investigate the systemic changes associated with early pregnancy by mapping the proteome of blood plasma at 14 days in pregnant and non-pregnant mares. Methods: Plasma proteomes were analysed in commercially bred pregnant (n = 17) and non-pregnant (n = 17) Thoroughbred mares at 14 days after ovulation, using high-resolution mass spectrometry. Day 14 histotroph and yolk sac fluid were also profiled and datasets were integrated through pathway analysis. Results: We identified 229 total protein IDs, with 12 increased and 10 decreased significantly in pregnant versus non-pregnant plasma. To gain functional insight, these data were aligned with proteomes of 14-day pregnant mare uterine fluid (n = 4; 1358 IDs) and conceptus fluid (soluble proteins within the yolk sac fluid; n = 4; 1152 IDs), and further interrogated using gene ontology databases and pathway analysis. Conclusions: These analyses identified consistent systemic changes in the mare's proteome that indicate a profound and specific immune response to early pregnancy, which appears to precede the systemic endocrine response to pregnancy. Integrated pathway analysis suggests that embryo-maternal interactions in early pregnancy may mimic elements of the virus-host interaction to modulate the maternal immune response. Transthyretin (TTR) and uteroglobin (SCGB1A1) were respectively down- and upregulated in plasma while also present in uterine fluid, and are proposed to be key proteins in early pregnancy establishment. These findings contribute significantly to our knowledge of early pregnancy in the mare and identify potential new avenues for developing clinical approaches to reduce early embryo loss.
© 2025 The Author(s). PROTEOMICS ‐ Clinical Applications published by Wiley‐VCH GmbH.
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Publication Date: 2025-01-27 PubMed ID: 39912552DOI: 10.1002/prca.202400095Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article examines the systemic changes that occur early in a mare’s pregnancy. By analyzing components such as the blood plasma, histotroph, and yolk sac fluid at 14 days post-ovulation, the study identifies alterations in the mare’s immune and endocrine responses, shedding light on the early stages of equine pregnancy and potential methods to curtail embryonic loss.

Objective and Methodology

  • The primary aim of this research was to uncover the systemic changes that happen during the early stages of a mare’s pregnancy, particularly focusing on the proteome of blood plasma 14 days post-ovulation.
  • An evaluation was performed comparing the plasma proteomes of commercially bred pregnant (17) and non-pregnant (17) Thoroughbred mares at 14 days after ovulation using high-resolution mass spectrometry.
  • The day 14 histotroph and yolk sac fluid were also profiled with the collected datasets subjected to pathway analysis to provide a comprehensive picture of the changes taking place.

Findings

  • During the analysis, 229 total protein IDs were identified, with 12 increased and 10 decreased significantly in the pregnant mares compared to the non-pregnant ones.
  • These data were aligned with proteomes present in uterine fluid and the fluid within the yolk sac (conceptus fluid) of 14-day pregnant mares, followed by extensive investigation using gene ontology databases and pathway analysis.
  • Notable systemic changes in the mare’s proteome were shown, unveiling a specific and significant immune response to early pregnancy, which seem to occur before the systemic endocrine response to pregnancy.

Conclusions and Further Insights

  • The integrated pathway analysis brought forth an interesting revelation – interactions between the embryo and its mother during early pregnancy could potentially exhibit characteristics resembling the virus-host interactions, manipulating the maternal immune response accordingly.
  • Two proteins, namely Transthyretin (TTR) and uteroglobin (SCGB1A1) were found to be respectively down- and up-regulated in plasma while also being present in the uterine fluid; these proteins are proposed to play essential roles in the establishment of early pregnancy.
  • These findings are significant to the understanding of early pregnancy in equines and pinpoint potential strategies to reduce early embryo loss in horses, which has been a major economic concern to the breeding industry.

Cite This Article

APA
Perera TRW, de Ruijter-Villani M, Gibb Z, Nixon B, Sheridan A, Stout TAE, Swegen A, Skerrett-Byrne DA. (2025). Systemic Changes in Early Pregnancy in the Mare: An Integrated Proteomic Analysis of Blood Plasma, Histotroph, and Yolk Sac Fluid at Day 14 Post-Ovulation. Proteomics Clin Appl, e202400095. https://doi.org/10.1002/prca.202400095

Publication

Proteomics. Clinical applications
ISSN: 1862-8354
NlmUniqueID: 101298608
Country: Germany
Language: English
Pages: e202400095

Researcher Affiliations

Perera, Tharangani R W
  • Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan, New South Wales, Australia.
  • Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia.
de Ruijter-Villani, Marta
  • Department of Clinical Sciences, Utrecht University, Utrecht, The Netherlands.
Gibb, Zamira
  • Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan, New South Wales, Australia.
  • Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia.
Nixon, Brett
  • Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan, New South Wales, Australia.
  • Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia.
Sheridan, Alecia
  • Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan, New South Wales, Australia.
  • Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia.
Stout, Tom A E
  • Department of Clinical Sciences, Utrecht University, Utrecht, The Netherlands.
Swegen, Aleona
  • Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan, New South Wales, Australia.
  • Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia.
Skerrett-Byrne, David A
  • Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan, New South Wales, Australia.
  • Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia.
  • Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
  • German Center for Diabetes Research (DZD), Neuherberg, Germany.

Grant Funding

  • PRJ-011748 / AgriFutures Australia Thoroughbred Horses Program
  • DE220100121 / Australian Research Council
  • FT220100557 / Australian Research Council

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