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Previously, we showed that heart and neural crest derivatives expressed transcript 2 ( Hand2 ) mRNA levels dramatically increase in mouse uterine endometrial stromal cells (ESCs) as they undergo decidualization  in vivo . However, to date, little is known about the expression and function of this transcription factor in mouse or human uterus decidualization. Therefore, this study was conducted to provide a more detailed assessment of  Hand2  gene expression and function in the mouse uterus during the peri-implantation period and also in mouse plus human ESCs during decidualization  in vitro . The results show that  Hand2  mRNA and protein levels increase in the mouse uterus during decidualization and this does not depend on the presence of a conceptus. Interestingly,  Hand2  mRNA and protein are present in ESCs adjacent to the luminal epithelium in the uterus prior to the onset of implantation. We find that progesterone is likely a regulator of  Hand2  expression during uterine sensitization of the mouse uterus. Finally,  Hand2  expression increases in mouse and human fibroblast cells as they undergo decidualization  in vitro . This expression is significantly increased in response to prostaglandin E 2 . In particular, reduction of  Hand2  expression in these cells using small hairpin RNA or small interfering RNA approaches results in the reduced extent of decidualization as shown by the reduced expression of a subset of decidualization markers. The results of this study support the hypothesis that  Hand2  expression not only plays an important role in decidualization but may also play a role in obtaining proper progesterone-dependent uterine sensitization required for implantation to begin.

Evidence for a conserved function of heart and neural crest derivatives expressed transcript 2 in mouse and human decidualization