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

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 mucos...

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Main Authors: Tomasz Jasiński, Łukasz Zdrojkowski, Graça Ferreira-Dias, Ewa Kautz, Edyta Juszczuk-Kubiak, Małgorzata Domino
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/13/7360
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author Tomasz Jasiński
Łukasz Zdrojkowski
Graça Ferreira-Dias
Ewa Kautz
Edyta Juszczuk-Kubiak
Małgorzata Domino
author_facet Tomasz Jasiński
Łukasz Zdrojkowski
Graça Ferreira-Dias
Ewa Kautz
Edyta Juszczuk-Kubiak
Małgorzata Domino
author_sort Tomasz Jasiński
collection DOAJ
description 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 (<i>ESR1</i>, <i>ESR2</i>) and progesterone receptors (<i>PGR</i>) in equine endometria to find relationships between the endocrine environment, NF-κB-pathway, and fibrosis. Endometrial samples (<i>n</i> = 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 <i>ESR1</i>, <i>ESR2</i>, and <i>PGR</i> decreased with the severity of endometrial fibrosis and degeneration of the endometrium. Moreover, differences in the transcription of <i>ESR1</i>, <i>ESR2</i>, and <i>PGR</i> 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 <i>ESR1</i>, <i>ESR2</i>, <i>PGR</i> 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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spelling doaj.art-712df1c44d924189a0d468d486c2c42b2023-11-23T20:12:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012313736010.3390/ijms23137360Molecular Mechanism of Equine Endometrosis: The NF-κB-Dependent Pathway Underlies the Ovarian Steroid Receptors’ DysfunctionTomasz Jasiński0Łukasz Zdrojkowski1Graça Ferreira-Dias2Ewa Kautz3Edyta Juszczuk-Kubiak4Małgorzata Domino5Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, PolandDepartment of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, PolandDepartmento de Morfologia e Função, CIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisbon, PortugalDepartment of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, PolandLaboratory of Biotechnology and Molecular Engineering, Department of Microbiology, Prof. Wacław Dąbrowski Institute of Agricultural and Food Biotechnology—State Research Institute, 02-532 Warsaw, PolandDepartment of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, PolandEndometrosis 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 (<i>ESR1</i>, <i>ESR2</i>) and progesterone receptors (<i>PGR</i>) in equine endometria to find relationships between the endocrine environment, NF-κB-pathway, and fibrosis. Endometrial samples (<i>n</i> = 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 <i>ESR1</i>, <i>ESR2</i>, and <i>PGR</i> decreased with the severity of endometrial fibrosis and degeneration of the endometrium. Moreover, differences in the transcription of <i>ESR1</i>, <i>ESR2</i>, and <i>PGR</i> 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 <i>ESR1</i>, <i>ESR2</i>, <i>PGR</i> 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.https://www.mdpi.com/1422-0067/23/13/7360NF-κBendometrosisreceptorestrogenprogesteroneendometrium
spellingShingle Tomasz Jasiński
Łukasz Zdrojkowski
Graça Ferreira-Dias
Ewa Kautz
Edyta Juszczuk-Kubiak
Małgorzata Domino
Molecular Mechanism of Equine Endometrosis: The NF-κB-Dependent Pathway Underlies the Ovarian Steroid Receptors’ Dysfunction
International Journal of Molecular Sciences
NF-κB
endometrosis
receptor
estrogen
progesterone
endometrium
title Molecular Mechanism of Equine Endometrosis: The NF-κB-Dependent Pathway Underlies the Ovarian Steroid Receptors’ Dysfunction
title_full Molecular Mechanism of Equine Endometrosis: The NF-κB-Dependent Pathway Underlies the Ovarian Steroid Receptors’ Dysfunction
title_fullStr Molecular Mechanism of Equine Endometrosis: The NF-κB-Dependent Pathway Underlies the Ovarian Steroid Receptors’ Dysfunction
title_full_unstemmed Molecular Mechanism of Equine Endometrosis: The NF-κB-Dependent Pathway Underlies the Ovarian Steroid Receptors’ Dysfunction
title_short Molecular Mechanism of Equine Endometrosis: The NF-κB-Dependent Pathway Underlies the Ovarian Steroid Receptors’ Dysfunction
title_sort molecular mechanism of equine endometrosis the nf κb dependent pathway underlies the ovarian steroid receptors dysfunction
topic NF-κB
endometrosis
receptor
estrogen
progesterone
endometrium
url https://www.mdpi.com/1422-0067/23/13/7360
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