Control of Uterine Cell Proliferation and Differentiation by C/EBPb: Functional Implications for Establishment of Early Pregnancy

Implantation of the embryo to the uterine wall is regulated by the concerted actions of maternal steroid hormones, progesterone (P) and estrogen (E). During early pregnancy, the stromal cells surrounding the implanted embryo proliferate and then undergo differentiation to form the "decidual" tissue, which protects and nurtures the embryo. The CCAAT enhancer-binding protein beta (C/EBPbeta), a transcription factor, has recently been identified as a novel mediator of the actions of E and P during decidualization. Female mice lacking C/EBPbeta gene are infertile and their uteri displayed a complete lack of response to a deciduogenic stimulus, indicating a critical role of this transcription factor in regulating the decidualization program. Initial studies indicate impairments in proliferation and differentiation of stromal cells in C/EBPbeta null uteri. C/EBPbeta is also essential for E-induced proliferation of uterine epithelial cells in nonpregnant mice. It is postulated that C/EBPbeta controls the expression of critical molecules that regulate proliferation and function of epithelial and stromal cells in the female reproductive tract during the establishment of early pregnancy.