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Animals : an open access journal from MDPI2023; 13(7); 1212; doi: 10.3390/ani13071212

5-Aza-2′-Deoxycytidine (5-Aza-dC, Decitabine) Inhibits Collagen Type I and III Expression in TGF-β1-Treated Equine Endometrial Fibroblasts.

Abstract: Endometrosis negatively affects endometrial function and fertility in mares, due to excessive deposition of type I (COL1) and type III (COL3) collagens. The pro-fibrotic transforming growth factor (TGF-β1) induces myofibroblast differentiation, characterized by α-smooth muscle actin (α-SMA) expression, and collagen synthesis. In humans, fibrosis has been linked to epigenetic mechanisms. To the best of our knowledge, this has not been described in mare endometrium. Therefore, this study aimed to investigate the in vitro epigenetic regulation in TGF-β1-treated mare endometrial fibroblasts and the use of 5-aza-2'-deoxycytidine (5-aza-dC), an epigenetic modifier, as a putative treatment option for endometrial fibrosis. Methods and Results: The in vitro effects of TGF-β1 and of 5-aza-dC on DNA methyltransferases (, and ), , , and transcripts were analyzed in endometrial fibroblasts, and COL1 and COL3 secretion in a co-culture medium. TGF-β1 upregulated transcripts and collagen secretion. In TGF-β1-treated endometrial fibroblasts, DNA methylation inhibitor 5-aza-dC decreased collagen transcripts and secretion, but not transcripts. Conclusion: These findings suggest a possible role of epigenetic mechanisms during equine endometrial fibrogenesis. The in vitro effect of 5-aza-dC on collagen reduction in TGF-β1-treated fibroblasts highlights this epigenetic involvement. This may pave the way to different therapeutic approaches for endometrosis.
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Publication Date: 2023-03-30 PubMed ID: 37048467PubMed Central: PMC10093662DOI: 10.3390/ani13071212Google Scholar: Lookup
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  • Journal Article

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 study investigates how an epigenetic modifier, 5-aza-2′-deoxycytidine (5-aza-dC), could potentially be used to treat endometrial fibrosis, a condition affecting the fertility in mares. Researchers studied the role of this modifier in the regulation of type I and type III collagens, known to significantly impact fibrosis in mares.

Research Purpose and Background

  • The purpose of this study was to explore the in vitro epigenetic regulation in transforming growth factor-beta-1 (TGF-β1) treated mare endometrial fibroblasts.
  • The researchers were specifically interested in studying the application of 5-aza-2′-deoxycytidine, an epigenetic modifier, as a potential treatment for endometrial fibrosis, a condition causing excessive collagen deposition.
  • While previous investigations have linked human fibrosis to various epigenetic mechanisms, similar studies have not been conducted on mares.
  • The condition significantly impacts fertility in mares due to hindered endometrial function.

Methods and Results

  • The research process involved analyzing the in vitro effects of TGF-β1 and 5-aza-dC on DNA methyltransferases and the secretion of Type I and III collagens in a co-culture medium of TGF-β1-treated endometrial fibroblasts.
  • TGF-β1 was observed upregulating the collagen secretion, indicating it played a significant role in endometrial fibrosis in mares.
  • Interestingly, the use of the DNA methylation inhibitor, 5-aza-dC, resulted in a decrease in collagen transcripts and secretion in TGF-β1-treated endometrial fibroblasts.

Conclusion and Potential Implications

  • The results suggest that epigenetic mechanisms may indeed play a role during equine endometrial fibrogenesis, and that 5-aza-dC may have an in vitro effect on collagen reduction in TGF-β1-treated fibroblasts.
  • The study potentially opens up novel therapeutic possibilities for endometrosis, with further research required to understand the clinical implications and side effects, if any, of 5-aza-dC.

Cite This Article

APA
Alpoim-Moreira J, Szóstek-Mioduchowska A, Słyszewska M, Rebordão MR, Skarzynski DJ, Ferreira-Dias G. (2023). 5-Aza-2′-Deoxycytidine (5-Aza-dC, Decitabine) Inhibits Collagen Type I and III Expression in TGF-β1-Treated Equine Endometrial Fibroblasts. Animals (Basel), 13(7), 1212. https://doi.org/10.3390/ani13071212

Publication

Animals : an open access journal from MDPI
ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 13
Issue: 7
PII: 1212

Researcher Affiliations

Alpoim-Moreira, Joana
  • CIISA-Center for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal.
  • Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal.
Szóstek-Mioduchowska, Anna
  • Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, Poland.
Słyszewska, Magda
  • Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, Poland.
Rebordão, Maria Rosa
  • CIISA-Center for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal.
  • Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal.
  • Polytechnic of Coimbra, Coimbra Agriculture School, 3045-601 Coimbra, Portugal.
Skarzynski, Dariusz J
  • Department of Animal Reproduction with Large Animal Clinic, Faculty of Veterinary Medicine, University of Environmental and Live Sciences, 50-366 Wrocław, Poland.
Ferreira-Dias, Graça
  • CIISA-Center for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal.
  • Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal.

Grant Funding

  • UID/CVT/00276/2020 / Fundau00e7u00e3o para a Ciu00eancia e Tecnologia
  • LA/0059/2020/AL4AnimalS / Fundau00e7u00e3o para a Ciu00eancia e Tecnologia
  • OPUS19 nr 2020/37/B/NZ9/03355 / Polish National Science Centre
  • 2022.09161.PTDC / Fundau00e7u00e3o para a Ciu00eancia e Tecnologia

Conflict of Interest Statement

The authors declare no conflicts of interest.

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Citations

This article has been cited 4 times.
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