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Isolation of Human Endometrial Stromal Cells for In Vitro Decidualization
Published on: September 1, 2018
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ARID1A Is Essential for Endometrial Function during Early Pregnancy.
Tae Hoon Kim1, Jung-Yoon Yoo1, Zhong Wang2
1Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University College of Human Medicine, Grand Rapids, Michigan, United States of America.
Plos Genetics
|September 18, 2015
Summary
Loss of the AT-rich interactive domain 1A gene (ARID1A) impairs fertility by increasing uterine epithelial proliferation. This ARID1A gene function is crucial for embryo implantation and successful pregnancy in female reproduction.
Area of Science:
- Reproductive Biology
- Genetics
- Gynecology
Background:
- Loss of the AT-rich interactive domain 1A gene (ARID1A) is common in endometriosis-associated ovarian cancers.
- ARID1A protein is reduced in the endometrium of women with endometriosis, a condition linked to infertility.
- The precise role of Arid1a in the female reproductive tract remains unclear.
Purpose of the Study:
- To investigate the physiological role of Arid1a in the uterus.
- To determine the impact of Arid1a loss on female reproductive functions, including fertility, uterine development, and embryo implantation.
Main Methods:
- Generated mice with conditional Arid1a ablation in progesterone receptor (PGR)-positive cells (Pgrcre/+Arid1af/f; Arid1ad/d).
- Assessed ovarian function, uterine development, embryo implantation, and decidualization in Arid1ad/d mice.
- Utilized microarray analysis to identify ARID1A-regulated genes.
- Examined epithelial proliferation, estrogen activity, and PGR expression in the uterus.
Main Results:
- Arid1ad/d mice exhibited normal ovarian function and uterine development but were sterile due to implantation and decidualization defects.
- Increased uterine epithelial proliferation was observed in Arid1ad/d mice.
- Arid1ad/d mice showed enhanced epithelial estrogen activity and reduced PGR expression, hindering uterine receptivity.
- Microarray analysis indicated ARID1A represses genes involved in cell cycle and DNA replication.
- ARID1A was found to positively regulate Klf15 expression with PGR to inhibit peri-implantation epithelial proliferation.
Conclusions:
- Arid1a plays a critical role in regulating uterine epithelial proliferation, essential for female fertility.
- ARID1A acts in concert with PGR to control epithelial proliferation during the peri-implantation period.
- This study reveals a novel signaling pathway for steroid hormone regulation in female reproduction and sheds light on hormonal dysregulation in disorders like endometriosis.
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