Loss of miR-29a impairs decidualization of endometrial stromal cells by TET3 mediated demethylation of Col1A1 promoter
Aixia Liu,
Mengmeng Jin,
Laidi Xie,
Mengyu Jing,
Ying Zhou,
Minyue Tang,
Tingting Lin,
Dimin Wang
Affiliations
Aixia Liu
Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, 1 Xueshi Road, Hangzhou 310006, PR China; Key Laboratory of Reproductive Genetics (Ministry of Education), Zhejiang University, Hangzhou 310006, PR China; Corresponding author
Mengmeng Jin
Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, 1 Xueshi Road, Hangzhou 310006, PR China
Laidi Xie
Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, 1 Xueshi Road, Hangzhou 310006, PR China
Mengyu Jing
Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, 1 Xueshi Road, Hangzhou 310006, PR China
Ying Zhou
Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, 1 Xueshi Road, Hangzhou 310006, PR China
Minyue Tang
Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, 1 Xueshi Road, Hangzhou 310006, PR China; Key Laboratory of Reproductive Genetics (Ministry of Education), Zhejiang University, Hangzhou 310006, PR China
Tingting Lin
Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, 1 Xueshi Road, Hangzhou 310006, PR China
Dimin Wang
Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, 1 Xueshi Road, Hangzhou 310006, PR China; Corresponding author
Summary: A conceptual framework for understanding abnormal endometrial decidualization, with considerable significance for the diagnosis and treatment of abnormal decidualization-related changes in non-receptive endometrium in implantation failure during early pregnancy is very important. Here, we found the expression levels of miR-29a in endometrial tissues were associated with the menstrual phases and pregnancy outcome. Inhibition of miR-29a led to decreased decidualization of endometrial stromal cells (ESCs) in vitro, whereas Tet methylcytosine dioxygenase 3 (TET3) and its potential demethylation target, the collagen type I alpha 1 chain (Col1A1), were restored. The binding capacity of TET3 to the Col1A1 promoter could be enhanced by the inhibition of miR-29a. Finally, deletion of TET3 rescued the inhibitory effect of the miR-29a antagomir on the proliferation of decidualized ESCs in vitro and embryo implantation in vivo. Thus, loss of miR-29a causes implantation failure because of the limitation of ESCs decidualization-related changes in non-receptive endometrium during early pregnancy.
