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Scientific reports2023; 13(1); 15938; doi: 10.1038/s41598-023-42149-3

The potential role of miRNAs and regulation of their expression in the development of mare endometrial fibrosis.

Abstract: Mare endometrial fibrosis (endometrosis), is one of the main causes of equine infertility. Despite the high prevalence, both ethology, pathogenesis and the nature of its progression remain poorly understood. Recent studies have shown that microRNAs (miRNAs) are important regulators in multiple cellular processes and functions under physiological and pathological circumstances. In this article, we reported changes in miRNA expression at different stages of endometrosis and the effect of transforming growth factor (TGF)-β1 on the expression of the most dysregulated miRNAs. We identified 1, 26, and 5 differentially expressed miRNAs (DEmiRs), in categories IIA (mild fibrosis), IIB (moderate fibrosis), and III (severe fibrosis) groups compared to category I (no fibrosis) endometria group, respectively (P < 0.05, log2FC ≥ 1.0/log2FC ≤  - 1.0). This study indicated the potential involvement of miRNAs in the regulation of the process associated to the development and progression of endometrosis. The functional enrichment analysis revealed, that DEmiRs target genes involved in the mitogen-activated protein kinases, Hippo, and phosphoinositide-3-kinase (PI3K)-Akt signalling pathways, focal adhesion, and extracellular matrix-receptor interaction. Moreover, we demonstrated that the most potent profibrotic cytokine-TGF-β1-downregulated novel-eca-miR-42 (P < 0.05) expression in fibroblasts derived from endometria at early-stage endometrosis (category IIA).
Publication Date: 2023-09-24 PubMed ID: 37743390PubMed Central: PMC10518347DOI: 10.1038/s41598-023-42149-3Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research study investigates the role of microRNAs and their expression in how endometrial fibrosis develops in mares, a significant cause of equine infertility.

Understanding the Scope of Research

  • This research primarily focuses on mare endometrial fibrosis, also known as endometrosis, a leading cause of infertility in horses. The condition’s ethology, pathogenesis, and progression nature are not yet completely understood.
  • In recent times, studies have shown that microRNAs (miRNAs) have essential roles in regulating various cellular processes and functions, whether under physiological or pathological conditions.

Methodology and Findings

  • The researchers monitored changes in microRNA (miRNA) expression at various stages of endometrosis and investigated the influence of a specific cellular growth factor, named transforming growth factor (TGF)-β1, on the expression of the most dysregulated miRNAs.
  • Through this, they identified several differentially expressed microRNAs (DEmiRs) in different stages of fibrosis, from mild to severe, and compared them to a control group with no fibrosis.
  • These findings suggested that microRNAs are potentially involved in controlling the procedures associated with the development and progression of endometrosis.

Implication of the Findings

  • The researchers did a functional enrichment analysis showing that the differentially expressed microRNAs target genes involved in various signalling pathways; mitogen-activated protein kinases, Hippo, and phosphoinositide-3-kinase (PI3K)-Akt, as well as focal adhesion and extracellular matrix-receptor interaction. These processes are crucial for a range of cellular activities.
  • Moreover, the researchers also found that TGF-β1, a highly profibrotic cytokine, inhibits the expression of the novel-eca-miR-42 microRNA in fibroblasts at an early stage of endometrosis. Understanding of this fundemental biological data helps build a foundation to develop potential therapeutic approaches for mare infertility caused by endometrosis.

Cite This Article

APA
Wójtowicz A, Molcan T, Lukasik K, Żebrowska E, Pawlina-Tyszko K, Gurgul A, Szmatoła T, Bugno-Poniewierska M, Ferreira-Dias G, Skarzynski DJ, Szóstek-Mioduchowska A. (2023). The potential role of miRNAs and regulation of their expression in the development of mare endometrial fibrosis. Sci Rep, 13(1), 15938. https://doi.org/10.1038/s41598-023-42149-3

Publication

ISSN: 2045-2322
NlmUniqueID: 101563288
Country: England
Language: English
Volume: 13
Issue: 1
Pages: 15938
PII: 15938

Researcher Affiliations

Wójtowicz, Anna
  • Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Tuwima 10, 10-748, Olsztyn, Poland.
Molcan, Tomasz
  • Molecular Biology Laboratory, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima 10, 10-748, Olsztyn, Poland.
Lukasik, Karolina
  • Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Tuwima 10, 10-748, Olsztyn, Poland.
Żebrowska, Ewelina
  • Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Tuwima 10, 10-748, Olsztyn, Poland.
Pawlina-Tyszko, Klaudia
  • Department of Animal Molecular Biology, National Research Institute of Animal Production, Cracow, Poland.
Gurgul, Artur
  • Department of Animal Reproduction, Anatomy and Genomics, The University of Agriculture in Krakow, Cracow, Poland.
Szmatoła, Tomasz
  • Department of Animal Molecular Biology, National Research Institute of Animal Production, Cracow, Poland.
  • Center for Experimental and Innovative Medicine, University of Agriculture in Krakow, Cracow, Poland.
Bugno-Poniewierska, Monika
  • Department of Animal Reproduction, Anatomy and Genomics, The University of Agriculture in Krakow, Cracow, Poland.
Ferreira-Dias, Graca
  • Faculty of Veterinary Medicine, CIISA - Center for Interdisciplinary Research in Animal Health, University of Lisbon, Lisbon, Portugal.
  • Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Lisbon, Portugal.
Skarzynski, Dariusz J
  • Department of Reproduction and Clinic of Farm Animals, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland.
Szóstek-Mioduchowska, Anna
  • Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Tuwima 10, 10-748, Olsztyn, Poland. a.szostek-mioduchowska@pan.olsztyn.pl.

MeSH Terms

  • Animals
  • Female
  • Horses
  • Humans
  • Uterine Diseases
  • Endometrium
  • Cytokines
  • Fibroblasts
  • MicroRNAs / genetics

Conflict of Interest Statement

The authors declare no competing interests.

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