Cell-cycle machinery is critical in regulating uterine steroid hormone for embryo implantation and development.

Proper embryo implantation is necessary for a successful pregnancy. In this issue of the JCI, Aljubran et al. identified the cell cycle regulatory protein cyclin A2 (CCNA2) as a factor in supporting embryo implantation and embryo development. Endometrial stromal cells showed higher levels of CCNA2 in patients undergoing assisted reproductive technology who had successful pregnancies. CCNA2 expression correlated with stromal cell proliferation and the expression of steroid hormone receptors for estrogen (ESR1, also known as ERα) and progesterone (PGR). Notably, loss of Ccna2 in mouse models resulted in infertility. The uteri of these mice were hypoplastic with reduced estrogen sensitivity, resulting in the disruption of stroma cell decidualization and loss of embryo viability after implantation. These findings demonstrate the importance of stroma cell proliferation in preparing the uterus for embryo implantation. They also identify CCNA2 as a coregulator of steroid hormone receptor signaling and suggest that impaired uterine stroma can underly early pregnancy loss.