Recent studies revealed that TMEM16A is involved in several reproductive processes, including ovarian estrogen secretion and ovulation, sperm motility and acrosome reaction, fertilization and myometrium contraction. However, little is known about the expression and function of TMEM16A in embryo implantation and decidualization. In this study, we focused on the expression and regulation of TMEM16A in mouse uterus during early pregnancy. We found that TMEM16A is upregulated in uterine endometrium in response to embryo implantation and decidualization. Progesterone treatment could induce TMEM16A expression in endometrial stromal cells through progesterone receptor/c-Myc pathway, which is blocked by progesterone receptor antagonist or the inhibitor of c-Myc signaling pathway. Inhibition of TMEM16A by small molecule inhibitor (T16Ainh-A01) resulted in impaired embryo implantation and decidualization in mice. Treatment with either specific siRNA of Tmem16a or T16Ainh-A01 inhibited the decidualization and proliferation of mouse endometrial stromal cells. In conclusion, our results revealed that TMEM16A is involved in embryo implantation and decidualization in mice, compromised function of TMEM16A may lead to impaired embryo implantation and decidualization.
Qianrong Qi, Yifan Yang, Kailin Wu and Qingzhen Xie
Xiao-Bo Wang, Qian-Rong Qi, Kai-Lin Wu and Qing-Zhen Xie
OPN is essential for blastocyst implantation and placentation. Previous study found that miR181a was increased while miR181b was downregulated in endometrium during decidualization. However, the information regarding their effects on decidualization in human endometrium is still limited. Here, we report a novel role of OPN and miR181b in uterine decidualization and pregnancy success in humans. The expression of OPN was high in endometrium in secretory phase and in vitro decidualized hESC, whereas miR181b expression was low in identical conditions. Further analysis confirmed that OPN expression was upregulated by cAMP and C/EBPβ signal pathway, while downregulated by miR181b. Increased OPN expression could promote the expression of decidualization-related and angiogenesis-related genes. Conversely, the processes of decidualization and angiogenesis in hESC were compromised by inhibiting OPN expression in vitro. OPN expression was repressed in implantation failure group when compared with successful pregnancy group in IVF/ICSI-ET cycles. These findings add a new line of evidence supporting the fact that OPN is involved in decidualization and pregnancy success.