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Endometrial epithelial ARID1A is critical for uterine gland function in early pregnancy establishment
Author(s) -
Marquardt Ryan M.,
Kim Tae Hoon,
Yoo JungYoon,
Teasley Hanna E.,
Fazleabas Asgerally T.,
Young Steven L.,
Lessey Bruce A.,
Arora Ripla,
Jeong JaeWook
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202002178r
Subject(s) - decidualization , foxa2 , arid1a , endometrium , endometriosis , biology , infertility , stat3 , endocrinology , medicine , cancer research , andrology , pregnancy , transcription factor , gene , signal transduction , microbiology and biotechnology , biochemistry , genetics , mutation
Though endometriosis and infertility are clearly associated, the pathophysiological mechanism remains unclear. Previous work has linked endometrial ARID1A loss to endometriosis‐related endometrial non‐receptivity. Here, we show in mice that ARID1A binds and regulates transcription of the Foxa2 gene required for endometrial gland function. Uterine‐specific deletion of Arid1a compromises gland development and diminishes Foxa2 and Lif expression. Deletion of Arid1a with Ltf‐iCre in the adult mouse endometrial epithelium preserves the gland development while still compromising the gland function. Mice lacking endometrial epithelial Arid1a are severely sub‐fertile due to defects in implantation, decidualization, and endometrial receptivity from disruption of the LIF‐STAT3‐EGR1 pathway. FOXA2 is also reduced in the endometrium of women with endometriosis in correlation with diminished ARID1A, and both ARID1A and FOXA2 are reduced in nonhuman primates induced with endometriosis. Our findings describe a role for ARID1A in the endometrial epithelium supporting early pregnancy establishment through the maintenance of gland function.