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Scientific reports2022; 12(1); 15616; doi: 10.1038/s41598-022-19958-z

Uterine extracellular vesicles as multi-signal messengers during maternal recognition of pregnancy in the mare.

Abstract: In contrast to other domestic mammals, the embryo-derived signal(s) leading to maternal recognition of pregnancy (MRP) are still unknow in the mare. We hypothesize that these embryonic signals could be packed into uterine extracellular vesicles (uEVs), acting as multi-signal messengers between the conceptus and the maternal tract, and contributing to MRP. To unveil these signals, the RNA and protein cargos of uEVs isolated from uterine lavages collected from pregnant mares (P; day 10, 11, 12 and 13 after ovulation) and cyclic control mares (C; day 10 and 13 after ovulation) were analyzed. Our results showed a fine-tuned regulation of the uEV cargo (RNAs and proteins), by the day of pregnancy, the estrous cycle, and even the size of the embryo. A particular RNA pattern was identified with specific increase on P12 related to immune system and hormonal response. Besides, a set of proteins as well as RNAs was highly enriched in EVs on P12 and P13. Differential abundance of miRNAs was also identified in P13-derived uEVs. Their target genes were linked to down- or upregulated genes in the embryo and the endometrium, exposing their potential origin. Our study identified for first time specific molecules packed in uEVs, which were previously associated to MRP in the mare, and thus bringing added value to the current knowledge. Further integrative and functional analyses will help to confirm the role of these molecules in uEVs during MRP in the mare.
© 2022. The Author(s).
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Publication Date: 2022-09-16 PubMed ID: 36114358PubMed Central: PMC9481549DOI: 10.1038/s41598-022-19958-zGoogle Scholar: Lookup
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  • Journal Article
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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 focuses on understanding the embryonic signals responsible for maternal recognition of pregnancy in horses, specifically, mares. It investigates the possible role of uterine extracellular vesicles, which act as messengers within the body, in transmitting these signals.

Research Aim and Hypothesis

  • The research aims to understand the still unknown embryonic signals responsible for triggering maternal recognition of pregnancy (MRP) in mares, something that is already well understood for other domestic animals.
  • The hypothesis proposed in the study suggests that these embryonic signals could be contained within uterine extracellular vesicles (uEVs). These uEVs could thus, in essence, serve as messengers between the conceptus (embryo) and the maternal tract, facilitating MRP.

Methodology

  • To test this hypothesis and gain insights into these embryonic signals, the researchers collected and analyzed the RNA and protein contents of uEVs from pregnant and cyclic control mares at different stages after ovulation.
  • The uEVs were collected through uterine lavages, and the samples were collected from the mares on days 10, 11, 12, 13 (for pregnant mares), and on days 10 and 13 for cyclic control mares.

Findings

  • The findings indicated that the contents of uEVs (both RNAs and proteins) showed regulation influenced by varied factors, namely, day of pregnancy, estrous cycle, and the size of the embryo.
  • The researchers discovered a specific RNA pattern that increased specifically on the 12th day of pregnancy, related to immune system and hormonal responses.
  • They also found a unique set of proteins and RNAs highly enriched in the extracellular vesicles collected on days 12 and 13 of pregnancy. Besides, they noticed changes in the abundance of miRNAs in uEVs derived on the 13th day of pregnancy.
  • These target genes of miRNAs, linked to downregulated or upregulated genes in both, the embryo and endometrium, hinted at their potential source, or origin.

Conclusion and Future Directions

  • The research concluded that it identified, for the first time, specific molecules packed in uEVs which had previously been associated with MRP in mares, thereby providing valuable insights.
  • In the future, further analysis, both integrative and functional, will help confirm the role of these molecules in uEVs during MRP in mares.

Cite This Article

APA
Rudolf Vegas A, Hamdi M, Podico G, Bollwein H, Fröhlich T, Canisso IF, Bauersachs S, Almiñana C. (2022). Uterine extracellular vesicles as multi-signal messengers during maternal recognition of pregnancy in the mare. Sci Rep, 12(1), 15616. https://doi.org/10.1038/s41598-022-19958-z

Publication

Scientific reports
ISSN: 2045-2322
NlmUniqueID: 101563288
Country: England
Language: English
Volume: 12
Issue: 1
Pages: 15616
PII: 15616

Researcher Affiliations

Rudolf Vegas, Alba
  • Functional Genomics Group, Institute of Veterinary Anatomy, Vetsuisse Faculty Zurich, University of Zurich, 8315, Lindau, ZH, Switzerland.
Hamdi, Meriem
  • Functional Genomics Group, Institute of Veterinary Anatomy, Vetsuisse Faculty Zurich, University of Zurich, 8315, Lindau, ZH, Switzerland.
Podico, Giorgia
  • Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, 61802, USA.
Bollwein, Heinrich
  • Clinic of Reproductive Medicine, Vetsuisse-Faculty, University of Zurich, 8315, Lindau, ZH, Switzerland.
Fröhlich, Thomas
  • Gene Center, Laboratory for Functional Genome Analysis, LMU Munich, 81377, Munich, Germany.
Canisso, Igor F
  • Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, 61802, USA.
Bauersachs, Stefan
  • Functional Genomics Group, Institute of Veterinary Anatomy, Vetsuisse Faculty Zurich, University of Zurich, 8315, Lindau, ZH, Switzerland.
Almiñana, Carmen
  • Functional Genomics Group, Institute of Veterinary Anatomy, Vetsuisse Faculty Zurich, University of Zurich, 8315, Lindau, ZH, Switzerland. carmen.alminanabrines@uzh.ch.

MeSH Terms

  • Animals
  • Embryo, Mammalian / metabolism
  • Endometrium / metabolism
  • Extracellular Vesicles / metabolism
  • Female
  • Horses
  • Mammals / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Pregnancy
  • Proteins / metabolism
  • Uterus / metabolism

Grant Funding

  • SNSF grant 31003A_173171 / Swiss National Science Foundation

Conflict of Interest Statement

The authors declare no competing interests.

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Citations

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