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Home / Equine Research Bank / Sci Rep / Ovarian steroids modulate mRNA expression of ECM associated ...
Scientific reports2025; 15(1); 538; doi: 10.1038/s41598-024-84250-1

Ovarian steroids modulate mRNA expression of ECM associated genes and collagen deposition induced by TGF β1 in equine endometrium in vitro.

Abstract: Equine endometrosis is a major cause of infertility in mares and is characterized by degenerative, functional and fibrotic changes in the endometrium with increased collagen (COL) deposition. Transforming growth factor (TGF)-β1 is one of the major pro-fibrotic factors involved in the excessive deposition of extracellular matrix (ECM) components in the equine endometrium. It has been demonstrated that ovarian steroids, specifically 17β-estradiol (E2) and progesterone (P4), not only regulate the cyclicity of the estrous cycle, but also have been implicated as anti- or pro-fibrotic factors. This study aimed to evaluate (i) the effect of E2 and P4 on the expression of ECM-associated genes including COL1A1, COL3A1, matrix metalloproteases (MMPs): MMP-1, MMP-2, MMP-3, MMP-9, and MMP-13, and tissue inhibitors of MMPs (TIMPs): TIMP-1 and TIMP-2 in equine endometrial fibroblasts, and (ii) the effect of ovarian steroids on TGF-β1-induced COL1 expression in equine endometrial explants from the follicular and mid-luteal phases of the estrous cycle. The mRNA expression of ECM-associated genes in endometrial fibroblasts and TGF-β1-induced COL1 expression in endometrial explants was modulated by ovarian steroids, with variations depending on the type of steroid and the duration of treatment. Moreover, P4 decreased TGF-β1-induced COL1 protein abundance in the mid-luteal phase of the estrous cycle after 48 h (p < 0.05). The results of our study indicate that during the estrous cycle, the ovarian steroids E2 or P4 may act directly on endometrial fibroblasts, thereby affecting the expression of genes involved in tissue remodeling, namely MMPs and TIMPs. Furthermore, P4 appears to affect not only the ECM-associated genes in endometrial fibroblasts, but also to attenuate the pro-fibrotic action of TGF-β1 in the mid-luteal stage of the estrous cycle.
© 2024. The Author(s).
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Publication Date: 2025-01-02 PubMed ID: 39747561PubMed Central: PMC11697027DOI: 10.1038/s41598-024-84250-1Google 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.

This research examines the role of ovarian steroids in influencing the expression of genes associated with extracellular matrix (ECM) components in the uterus (endometrium) of horses. It particularly focuses on how the steroids affect the excessive deposition of collagen, a condition known as endometrosis, which is a leading cause of infertility in mares.

Structure of the Study

  • The researchers aimed primarily to investigate two aspects:
    • The impact of ovarian steroids (17β-estradiol (E2) and progesterone (P4)) on the expression of ECM-associated genes housed in equine fibroblasts present in the endometrium. These genes include COL1A1, COL3A1, various matrix metalloproteases (MMPs), and tissue inhibitors of MMPs (TIMPs).
    • The effect of ovarian steroids on the increase of COL1 expression caused by transforming growth factor (TGF)-β1 in the endometrium of horses during two specific parts of the estrous cycle: the follicular and mid-luteal phases.

Key Findings

  • The team found that the impact of these steroids varied based on the type of steroid used and the length of treatment. In particular, expression of ECM-associated genes in fibroblasts and TGF-β1-induced COL1 expression in endometriums were both found to be susceptible to change due to the steroids.
  • Progesterone (P4) was found to reduce the abundance of COL1 protein in the mid-luteal phase of the estrous cycle after a period of 48 hours. This discovery is statistically significant (p < 0.05).

Implications

  • The results of this research highlight a potential direct role of ovarian steroids E2 and P4 on the equine endometrium. These steroids seemingly can alter the expression of genes that are involved in tissue remodelling, such as all types of MMP and TIMP.
  • Further developing our understanding of this process, this research adds that P4 also appears to mitigate the function of TGF-β1 as a pro-fibrotic agent during the mid-luteal stage of the estrous cycle. This finding may pave the way for new strategies in the treatment of endometrosis affecting horses, or similar conditions in other species.

Cite This Article

APA
Ana A, Agnieszka S, Marta CP, Pawel K, Dariusz S, Graça FD, Szóstek-Mioduchowska A. (2025). Ovarian steroids modulate mRNA expression of ECM associated genes and collagen deposition induced by TGF β1 in equine endometrium in vitro. Sci Rep, 15(1), 538. https://doi.org/10.1038/s41598-024-84250-1

Publication

Scientific reports
ISSN: 2045-2322
NlmUniqueID: 101563288
Country: England
Language: English
Volume: 15
Issue: 1
Pages: 538
PII: 538

Researcher Affiliations

Ana, Amaral
  • CIISA-Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade Técnica, Lisbon, 1300-477, Portugal. ana.amaral@fmv.ulisboa.pt.
  • Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Lisbon, 1300-477, Portugal. ana.amaral@fmv.ulisboa.pt.
  • Comprehensive Health Research Centre (CHRC), Évora, 7000-811, Portugal. ana.amaral@fmv.ulisboa.pt.
Agnieszka, Sadowska
  • Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, 10-748, Poland.
Marta, Cerveira-Pinto
  • CIISA-Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade Técnica, Lisbon, 1300-477, Portugal.
  • Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Lisbon, 1300-477, Portugal.
Pawel, Kordowitzki
  • Department of Basic and Preclinical Sciences, Institute for Veterinary Medicine, Nicolaus Copernicus University, ul. Gagarina 1, Torun, 87-100, Poland.
  • Department of Cell Biology, Blavatnik Institute, Harvard Medical School, 25 Shattuck Street, Boston, 02115240, USA.
Dariusz, Skarzynski
  • Department of Reproduction and Farm Animals Clinic, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Live Sciences, Wroclaw, Poland.
Graça, Ferreira-Dias
  • CIISA-Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade Técnica, Lisbon, 1300-477, Portugal.
  • Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Lisbon, 1300-477, Portugal.
Szóstek-Mioduchowska, Anna
  • Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, 10-748, Poland.

MeSH Terms

  • Animals
  • Female
  • Horses
  • Endometrium / metabolism
  • Endometrium / drug effects
  • Endometrium / pathology
  • Transforming Growth Factor beta1 / metabolism
  • Transforming Growth Factor beta1 / genetics
  • Estradiol / pharmacology
  • Progesterone / pharmacology
  • Progesterone / metabolism
  • Extracellular Matrix / metabolism
  • RNA, Messenger / metabolism
  • RNA, Messenger / genetics
  • Matrix Metalloproteinases / metabolism
  • Matrix Metalloproteinases / genetics
  • Collagen / metabolism
  • Collagen / genetics
  • Estrous Cycle / drug effects
  • Gene Expression Regulation / drug effects
  • Ovary / metabolism
  • Ovary / drug effects
  • Ovary / pathology
  • Fibroblasts / metabolism
  • Fibroblasts / drug effects

Grant Funding

  • UIDB/00276/2020 / Fundau00e7u00e3o para a Ciu00eancia e a Tecnologia
  • UIDB/00276/2020 / Fundau00e7u00e3o para a Ciu00eancia e a Tecnologia
  • UIDB/00276/2020 / Fundau00e7u00e3o para a Ciu00eancia e a Tecnologia
  • BPN/BPT/2021/1/00026/U/00001 / Narodowa Agencja Wymiany Akademickiej
  • BPN/BPT/2021/1/00026/U/00001 / Narodowa Agencja Wymiany Akademickiej
  • BPN/BPT/2021/1/00026/U/00001 / Narodowa Agencja Wymiany Akademickiej
  • FBW/8/2023 / IAR&FR
  • FBW/8/2023 / IAR&FR
  • FBW/8/2023 / IAR&FR

Conflict of Interest Statement

Declarations. Competing interests: No conflict of interest. Ethics approval and consent to participate: The samples were collected according to the European mandates (EFSA, AHAW/04–027). The materials collected were reviewed and accepted following the guidelines of the Local Ethics Committee for Experiments on Animals in Olsztyn, Poland (Agreements 51/2011). Consent for publication: Not applicable.

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