Paired‐like Homeodomain Transcription Factor 2 Affects Endometrial Cell Function and Embryo Implantation Through the Wnt/β‐catenin Pathway

The successful implantation of embryos is crucial for pregnancy in mammals. This complex process is inevitably dependent on the development of the endometrium. The paired‐like homeodomain transcription factor 2 (PITX2) is involved in a variety of biological processes, but whether it is involved in embryo implantation has not been reported. In this study, we aimed to investigate uterine expression and regulation of PITX2 during implantation. We found that PITX2 was elevated in the human endometrium in the secretory phase. The results of the pregnant mouse models showed that PITX2 expression was spatiotemporal in mouse endometrial tissue throughout peri‐implantation period, and it was significantly upregulated at the time of implantation. Interestingly, PITX2 was mainly localized to the glandular epithelium cells on D2.5‐3.5 of pregnancy, while D5.5‐6.5 was largely expressed in stromal cells. In vitro, PITX2 regulated endometrial cells proliferation, migration, invasion, and other functions through the Wnt/β‐catenin signaling pathway. In addition, a significant decrease in the rate of embryo implantation was observed after injecting PITX2 small interfering RNA into the uterine horn. These results demonstrate the effects of PITX2 on the physiological function of endometrial cells and embryo implantation, suggesting a role in the endometrial regulatory mechanism during implantation.