Spatiotemporal endometrial transcriptome analysis revealed the luminal epithelium as key player during initial maternal recognition of pregnancy in the mare.
Abstract: During the period of maternal recognition of pregnancy (MRP) in the mare, the embryo needs to signal its presence to the endometrium to prevent regression of the corpus luteum and prepare for establishment of pregnancy. This is achieved by mechanical stimuli and release of various signaling molecules by the equine embryo while migrating through the uterus. We hypothesized that embryo's signals induce changes in the endometrial gene expression in a highly cell type-specific manner. A spatiotemporal transcriptomics approach was applied combining laser capture microdissection and low-input-RNA sequencing of luminal and glandular epithelium (LE, GE), and stroma of biopsy samples collected from days 10-13 of pregnancy and the estrous cycle. Two comparisons were performed, samples derived from pregnancies with conceptuses ≥ 8 mm in diameter (comparison 1) and conceptuses ≤ 8 mm (comparison 2) versus samples from cyclic controls. The majority of gene expression changes was identified in LE and much lower numbers of differentially expressed genes (DEGs) in GE and stroma. While 1253 DEGs were found for LE in comparison 1, only 248 were found in comparison 2. Data mining mainly focused on DEGs in LE and revealed regulation of genes related to prostaglandin transport, metabolism, and signaling, as well as transcription factor families that could be involved in MRP. In comparison to other mammalian species, differences in regulation of genes involved in epithelial barrier formation and conceptus attachment and implantation reflected the unique features of equine reproduction at the time of MRP at the molecular level.
© 2021. The Author(s).
Publication Date: 2021-11-16 PubMed ID: 34785745PubMed Central: PMC8595723DOI: 10.1038/s41598-021-01785-3Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research paper examines how molecular signals from a horse embryo induce specific gene expression changes in the endometrium (inner lining of the uterus) during maternal recognition of pregnancy, which help prevent early pregnancy loss and aid establishment of successful pregnancy.
Study Objective and Methodology
- The researchers intended to investigate how an equine embryo’s signals change the gene expressions of the mare’s endometrial cells during the period of maternal recognition of pregnancy (MRP), a critical stage in which the female reproductive system recognizes the presence of an embryo.
- They employed a spatiotemporal transcriptomics approach, using laser capture microdissection to extract specific cell types (luminal and glandular epithelium or stroma) from biopsy samples obtained between the 10th and 13th days of pregnancy and the estrous cycle.
- The gene expression profiles of these cell types were analyzed using low-input-RNA sequencing, and comparisons were made between endometrial samples containing embryos larger than 8 mm, those less than 8mm, and control samples from non-pregnant cycles.
Key Findings
- The study found that the majority of gene expression changes occurred in the luminal epithelium (LE), while fewer changes were noted in the glandular endometrium (GE) and the stroma.
- Compared to samples from non-pregnant cycles, there were 1,253 differentially expressed genes (DEGs) in the LE with embryonic presence greater than 8mm (comparison 1), while only 248 DEGs in the ones with embryos less than 8mm (comparison 2).
- Further examination of the DEGs in LE revealed the regulation of genes related to prostaglandin transport, metabolism, and signaling, as well as certain transcription factor families which could potentially play important roles during the MRP stage.
Research Implications
- This research revealed significant variance in the regulation of genes involved in epithelial barrier formation, conceptus attachment, and implantation between horses and other mammalian species. These differences reflect the unique aspects of equine reproduction at the molecular level during MRP.
- The outcomes contribute to a better understanding of equine reproduction and may help in further refining reproductive treatments for mares and potentially for other mammals as well.
Cite This Article
APA
Rudolf Vegas A, Podico G, Canisso IF, Bollwein H, Almiñana C, Bauersachs S.
(2021).
Spatiotemporal endometrial transcriptome analysis revealed the luminal epithelium as key player during initial maternal recognition of pregnancy in the mare.
Sci Rep, 11(1), 22293.
https://doi.org/10.1038/s41598-021-01785-3 Publication
Researcher Affiliations
- Institute of Veterinary Anatomy and Clinic of Reproductive Medicine, Department for Farm Animals, Vetsuisse Faculty Zurich, University of Zurich, Lindau, Switzerland.
- Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois Urbana Champaign, Urbana, IL, USA.
- Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois Urbana Champaign, Urbana, IL, USA.
- Clinic of Reproductive Medicine, Department for Farm Animals, Vetsuisse Faculty Zurich, University of Zurich, Lindau, Switzerland.
- Institute of Veterinary Anatomy, Vetsuisse Faculty, University of Zurich, Lindau, Switzerland.
- Institute of Veterinary Anatomy, Vetsuisse Faculty, University of Zurich, Lindau, Switzerland. stefan.bauersachs@uzh.ch.
MeSH Terms
- Animals
- Embryo, Mammalian
- Endometrium / metabolism
- Female
- Horses
- Pregnancy
- Pregnancy, Animal
- Transcriptome
Grant Funding
- Project 2018-03 / Pro Pferd Foundation
- 31003A_173171 / Schweizerischer Nationalfonds zur Fu00f6rderung der Wissenschaftlichen Forschung
Conflict of Interest Statement
The authors declare no competing interests.
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Citations
This article has been cited 6 times.- Vegas AR, Podico G, Canisso IF, Bollwein H, Fröhlich T, Bauersachs S, Almiñana C. Dynamic regulation of the transcriptome and proteome of the equine embryo during maternal recognition of pregnancy. FASEB Bioadv 2022 Dec;4(12):775-797.
- Rudolf Vegas A, Hamdi M, Podico G, Bollwein H, Fröhlich T, Canisso IF, Bauersachs S, Almiñana C. Uterine extracellular vesicles as multi-signal messengers during maternal recognition of pregnancy in the mare. Sci Rep 2022 Sep 16;12(1):15616.
- Kertz NC, Banerjee P, Dyce PW, Rodning SP, Diniz WJS. Endometrial Signatures of Subfertility in Beef Heifers Reveal Dysregulation of MAPK Signaling and Ciliary Function. Genes (Basel) 2025 Nov 3;16(11).
- Siemieniuch-Tartanus M. The early pregnancy in mares - What do we still not know?. Vet Anim Sci 2025 Jun;28:100441.
- Lawson EF, Pickford R, Aitken RJ, Gibb Z, Grupen CG, Swegen A. Mapping the lipidomic secretome of the early equine embryo. Front Vet Sci 2024;11:1439550.
- de Castro T, van Heule M, Domingues RR, Jacob JCF, Daels PF, Meyers SA, Conley AJ, Dini P. Embryo-endometrial interaction associated with the location of the embryo during the mobility phase in mares. Sci Rep 2024 Feb 7;14(1):3151.
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