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Endometrial Epithelial ARID1A Is Required for Uterine Immune Homeostasis during Early Pregnancy

A growing body of work suggests epigenetic dysregulation contributes to endometriosis pathophysiology and female infertility. The chromatin remodeling complex subunit AT-rich interaction domain 1A (ARID1A) must be properly expressed to maintain normal uterine function. Endometrial epithelial ARID1A...

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Autores principales: Marquardt, Ryan M., Ahn, Soo Hyun, Reske, Jake J., Chandler, Ronald L., Petroff, Margaret G., Kim, Tae Hoon, Jeong, Jae-Wook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181301/
https://www.ncbi.nlm.nih.gov/pubmed/35682747
http://dx.doi.org/10.3390/ijms23116067
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author Marquardt, Ryan M.
Ahn, Soo Hyun
Reske, Jake J.
Chandler, Ronald L.
Petroff, Margaret G.
Kim, Tae Hoon
Jeong, Jae-Wook
author_facet Marquardt, Ryan M.
Ahn, Soo Hyun
Reske, Jake J.
Chandler, Ronald L.
Petroff, Margaret G.
Kim, Tae Hoon
Jeong, Jae-Wook
author_sort Marquardt, Ryan M.
collection PubMed
description A growing body of work suggests epigenetic dysregulation contributes to endometriosis pathophysiology and female infertility. The chromatin remodeling complex subunit AT-rich interaction domain 1A (ARID1A) must be properly expressed to maintain normal uterine function. Endometrial epithelial ARID1A is indispensable for pregnancy establishment in mice through regulation of endometrial gland function; however, ARID1A expression is decreased in infertile women with endometriosis. We hypothesized that ARID1A performs critical operations in the endometrial epithelium necessary for fertility besides maintaining gland function. To identify alterations in uterine gene expression resulting from loss of epithelial ARID1A, we performed RNA-sequencing analysis on pre-implantation uteri from Ltf(iCre/+)Arid1a(f/f) and control mice. Differential expression analysis identified 4181 differentially expressed genes enriched for immune-related ingenuity canonical pathways including agranulocyte adhesion and diapedesis and natural killer cell signaling. RT-qPCR confirmed an increase in pro-inflammatory cytokine and macrophage-related gene expression but a decrease in natural killer cell signaling. Immunostaining confirmed a uterus-specific increase in macrophage infiltration. Flow cytometry delineated an increase in inflammatory macrophages and a decrease in uterine dendritic cells in Ltf(iCre/+)Arid1a(f/f) uteri. These findings demonstrate a role for endometrial epithelial ARID1A in suppressing inflammation and maintaining uterine immune homeostasis, which are required for successful pregnancy and gynecological health.
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spelling pubmed-91813012022-06-10 Endometrial Epithelial ARID1A Is Required for Uterine Immune Homeostasis during Early Pregnancy Marquardt, Ryan M. Ahn, Soo Hyun Reske, Jake J. Chandler, Ronald L. Petroff, Margaret G. Kim, Tae Hoon Jeong, Jae-Wook Int J Mol Sci Article A growing body of work suggests epigenetic dysregulation contributes to endometriosis pathophysiology and female infertility. The chromatin remodeling complex subunit AT-rich interaction domain 1A (ARID1A) must be properly expressed to maintain normal uterine function. Endometrial epithelial ARID1A is indispensable for pregnancy establishment in mice through regulation of endometrial gland function; however, ARID1A expression is decreased in infertile women with endometriosis. We hypothesized that ARID1A performs critical operations in the endometrial epithelium necessary for fertility besides maintaining gland function. To identify alterations in uterine gene expression resulting from loss of epithelial ARID1A, we performed RNA-sequencing analysis on pre-implantation uteri from Ltf(iCre/+)Arid1a(f/f) and control mice. Differential expression analysis identified 4181 differentially expressed genes enriched for immune-related ingenuity canonical pathways including agranulocyte adhesion and diapedesis and natural killer cell signaling. RT-qPCR confirmed an increase in pro-inflammatory cytokine and macrophage-related gene expression but a decrease in natural killer cell signaling. Immunostaining confirmed a uterus-specific increase in macrophage infiltration. Flow cytometry delineated an increase in inflammatory macrophages and a decrease in uterine dendritic cells in Ltf(iCre/+)Arid1a(f/f) uteri. These findings demonstrate a role for endometrial epithelial ARID1A in suppressing inflammation and maintaining uterine immune homeostasis, which are required for successful pregnancy and gynecological health. MDPI 2022-05-28 /pmc/articles/PMC9181301/ /pubmed/35682747 http://dx.doi.org/10.3390/ijms23116067 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Marquardt, Ryan M.
Ahn, Soo Hyun
Reske, Jake J.
Chandler, Ronald L.
Petroff, Margaret G.
Kim, Tae Hoon
Jeong, Jae-Wook
Endometrial Epithelial ARID1A Is Required for Uterine Immune Homeostasis during Early Pregnancy
title Endometrial Epithelial ARID1A Is Required for Uterine Immune Homeostasis during Early Pregnancy
title_full Endometrial Epithelial ARID1A Is Required for Uterine Immune Homeostasis during Early Pregnancy
title_fullStr Endometrial Epithelial ARID1A Is Required for Uterine Immune Homeostasis during Early Pregnancy
title_full_unstemmed Endometrial Epithelial ARID1A Is Required for Uterine Immune Homeostasis during Early Pregnancy
title_short Endometrial Epithelial ARID1A Is Required for Uterine Immune Homeostasis during Early Pregnancy
title_sort endometrial epithelial arid1a is required for uterine immune homeostasis during early pregnancy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181301/
https://www.ncbi.nlm.nih.gov/pubmed/35682747
http://dx.doi.org/10.3390/ijms23116067
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