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

International Journal of Molecular Sciences

Margaret G. Petroff¹  Tae Hoon Kim²  Jae-Wook Jeong²  Ronald L. Chandler²  Jake J. Reske²  Ryan M. Marquardt²  Soo Hyun Ahn³ 

[1] Cell and Molecular Biology Program, College of Natural Science, Michigan State University, East Lansing, MI 48824, USA;Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI 49503, USA;Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA;

关键词: endometrium;    infertility;    immunology;    inflammation;    endometriosis;    ARID1A;   

DOI  :  10.3390/ijms23116067

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown