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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MDPI AG
2022-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/11/6067 |
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| author | Ryan M. Marquardt Soo Hyun Ahn Jake J. Reske Ronald L. Chandler Margaret G. Petroff Tae Hoon Kim Jae-Wook Jeong |
| author_facet | Ryan M. Marquardt Soo Hyun Ahn Jake J. Reske Ronald L. Chandler Margaret G. Petroff Tae Hoon Kim Jae-Wook Jeong |
| author_sort | Ryan M. Marquardt |
| collection | DOAJ |
| 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 <i>Ltf<sup>iCre/+</sup>Arid1a<sup>f/f</sup></i> 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 <i>Ltf<sup>iCre/+</sup>Arid1a<sup>f/f</sup></i> 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. |
| first_indexed | 2024-03-10T01:16:27Z |
| format | Article |
| id | doaj.art-c2134e8a6aa5419ebbbc30573cffd9aa |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:16:27Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c2134e8a6aa5419ebbbc30573cffd9aa2023-11-23T14:09:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012311606710.3390/ijms23116067Endometrial Epithelial ARID1A Is Required for Uterine Immune Homeostasis during Early PregnancyRyan M. Marquardt0Soo Hyun Ahn1Jake J. Reske2Ronald L. Chandler3Margaret G. Petroff4Tae Hoon Kim5Jae-Wook Jeong6Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI 49503, USADepartment of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USADepartment of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI 49503, USADepartment of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI 49503, USACell and Molecular Biology Program, College of Natural Science, Michigan State University, East Lansing, MI 48824, USADepartment of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI 49503, USADepartment of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI 49503, USAA 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 <i>Ltf<sup>iCre/+</sup>Arid1a<sup>f/f</sup></i> 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 <i>Ltf<sup>iCre/+</sup>Arid1a<sup>f/f</sup></i> 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.https://www.mdpi.com/1422-0067/23/11/6067endometriuminfertilityimmunologyinflammationendometriosisARID1A |
| spellingShingle | Ryan M. Marquardt Soo Hyun Ahn Jake J. Reske Ronald L. Chandler Margaret G. Petroff Tae Hoon Kim Jae-Wook Jeong Endometrial Epithelial ARID1A Is Required for Uterine Immune Homeostasis during Early Pregnancy International Journal of Molecular Sciences endometrium infertility immunology inflammation endometriosis ARID1A |
| 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 | endometrium infertility immunology inflammation endometriosis ARID1A |
| url | https://www.mdpi.com/1422-0067/23/11/6067 |
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