Uterine Prx2 restrains decidual differentiation through inhibiting lipolysis in mice

Uterine decidualization, characterized as extensive stromal cell proliferation, differentiation and polyploidization, is a crucial event for successful pregnancy and is tightly regulated by many different molecules and pathways. Prx2, an evolutionarily conserved homeobox transcription factor expressed in both embryos and adults, plays an important role during mesenchymal cell differentiation. However, it remains unclear what the exact function of Prx2 is in the uterine stromal cells, one type of mesenchymal cells. In the present study, employing in vivo and in vitro stromal cell decidualization models, combining adenovirus-mediated overexpression of Prx2, we found that the expression of Prx2 is initiated in the uterine stromal cells once the blastocyst attached to the epithelium and is always detected around the differentiated decidual zone in the anti-mesometrium of the uterus during post-implantation uterine development. Also, overexpression of Prx2 disturbed stromal-decidual differentiation, which is reflected by the decreased expression of decidual/trophoblast prolactin-related protein (Dtprp), the marker for uterine decidualization in mice. Further, we demonstrate that Prx2 overexpression disturbs lipolysis, leading to lipid droplets accumulation in uterine stromal cells, partially mediated by downregulated expression of adipocyte triglyceride lipase. Collectively, these data indicate that uterine Prx2 restrains uterine decidual differentiation through regulating lipid metabolism.