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Home / Equine Research Bank / Int J Mol Sci / Molecular Mechanism of Equine Endometrosis: The NF-κB-...
International journal of molecular sciences2022; 23(13); 7360; doi: 10.3390/ijms23137360

Molecular Mechanism of Equine Endometrosis: The NF-κB-Dependent Pathway Underlies the Ovarian Steroid Receptors’ Dysfunction.

Abstract: Endometrosis is a frequently occurring disease decreasing mares' fertility. Thus, it is an important disease of the endometrium associated with epithelial and stromal cell alterations, endometrium gland degeneration and periglandular fibrosis. Multiple degenerative changes are found in uterine mucosa, the endometrium. However, their pathogenesis is not well known. It is thought that nuclear factor-κB (NF-κB), a cell metabolism regulator, and its activation pathways take part in it. The transcription of the profibrotic pathway genes of the NF-κB in fibrotic endometria differed between the follicular (FLP) and mid-luteal (MLP) phases of the estrous cycle, as well as with fibrosis progression. This study aimed to investigate the transcription of genes of estrogen (, ) and progesterone receptors () in equine endometria to find relationships between the endocrine environment, NF-κB-pathway, and fibrosis. Endometrial samples ( = 100), collected in FLP or MLP, were classified histologically, and examined using quantitative PCR. The phase of the cycle was determined through the evaluation of ovarian structures and hormone levels (estradiol, progesterone) in serum. The transcription of , , and decreased with the severity of endometrial fibrosis and degeneration of the endometrium. Moreover, differences in the transcription of , , and were noted between FLP and MLP in the specific categories and histopathological type of equine endometrosis. In FLP and MLP, specific moderate and strong correlations between , , and genes of the NF-κB pathway were evidenced. The transcription of endometrial steroid receptors can be subjected to dysregulation with the degree of equine endometrosis, especially in both destructive types of endometrosis, and mediated by the canonical NF-κB pathway depending on the estrous cycle phase.
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Publication Date: 2022-07-01 PubMed ID: 35806363PubMed Central: PMC9266418DOI: 10.3390/ijms23137360Google 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.

The researchers investigated a common disease in mares known as endometrosis, which negatively impacts their fertility. They aimed to identify relationships between hormonal changes, a certain metabolic pathway called NF-κB, and fibrosis, in order to understand the disease progression and to identify potential targets for treatment.

Disease Overview

  • In this study, the researchers focused on endometrosis, a common disease in mares that frequently affects their ability to conceive and carry a pregnancy to term.
  • Endometrosis is characterized by alterations to the epithelial and stromal cells in the endometrium, the inner lining of the uterus, as well as the degeneration of endometrium glands and periglandular fibrosis, which refers to the development of excess fibrous connective tissue in an organ.

Role of the NF-κB Pathway in Endometrosis

  • The researchers postulated that the activation of a cell metabolism regulator, nuclear factor-κB (NF-κB), could be involved in the pathogenesis, or the biological mechanism that leads to the development of this disease.
  • They found that the transcription, or the process of creating an RNA copy of a sequence of DNA, of profibrotic pathway genes of the NF-κB in the fibrotic endometria differ between the follicular phase (when an egg is developing) and the mid-luteal phase (after ovulation) of the menstrual cycle, and also as fibrosis progresses.

Investigation of Estrogen and Progesterone Receptors in Equine Endometria

  • With this understanding, the study aimed to examine the transcription of genes of estrogen and progesterone receptors in samples of equine endometria, and establish whether there were any correlations between hormonal changes, the NF-κB-pathway, and fibrosis.
  • The researchers found that the transcription of the receptors for both estrogen and progesterone reduced in line with the severity of endometrial fibrosis and degeneration of the endometrium.
  • Moreover, they noted differences in the transcription of these receptors between the follicular phase and the mid-luteal phase of the estrous cycle, which were also associated with the extent and type of endometrosis observed.
  • In both the follicular phase and the mid-luteal phase, there were correlations between the receptors for estrogen and progesterone and genes of the NF-κB pathway.
  • The researchers concluded that the regulation of endometrial steroid receptors can be affected by the degree of equine endometrosis, particularly in the most destructive types of endometrosis, and it likely involves the NF-κB pathway, depending on the phase of the estrous cycle.

Cite This Article

APA
Jasiński T, Zdrojkowski Ł, Ferreira-Dias G, Kautz E, Juszczuk-Kubiak E, Domino M. (2022). Molecular Mechanism of Equine Endometrosis: The NF-κB-Dependent Pathway Underlies the Ovarian Steroid Receptors’ Dysfunction. Int J Mol Sci, 23(13), 7360. https://doi.org/10.3390/ijms23137360

Publication

International journal of molecular sciences
ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 23
Issue: 13
PII: 7360

Researcher Affiliations

Jasiński, Tomasz
  • Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, Poland.
Zdrojkowski, Łukasz
  • Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, Poland.
Ferreira-Dias, Graça
  • Departmento de Morfologia e Função, CIISA-Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisbon, Portugal.
Kautz, Ewa
  • Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, Poland.
Juszczuk-Kubiak, Edyta
  • Laboratory of Biotechnology and Molecular Engineering, Department of Microbiology, Prof. Wacław Dąbrowski Institute of Agricultural and Food Biotechnology-State Research Institute, 02-532 Warsaw, Poland.
Domino, Małgorzata
  • Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, Poland.

MeSH Terms

  • Animals
  • Endometrium / metabolism
  • Estrous Cycle / genetics
  • Female
  • Fibrosis
  • Horses
  • Humans
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Ovarian Diseases / metabolism
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / metabolism
  • Receptors, Steroid / genetics
  • Receptors, Steroid / metabolism

Grant Funding

  • 2018/02/X/NZ4/00101 / National Science Center

Conflict of Interest Statement

The authors declare no conflict of interest.

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Citations

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