The progesterone receptor regulates implantation, decidualization, and glandular development via a complex paracrine signaling network

Many women are affected by infertility and reproductive-associated disease such as endometriosis or endometrial cancer. Successful pregnancy is dependent on a healthy uterus that is fit to receive and support a fertilized embryo. The uterus is an endocrine organ, responsive to the presence of the ovarian steroid hormones, estrogen and progesterone, which activate transcription of target genes through the binding of their cognate receptors, the estrogen receptor and the progesterone receptor. Progesterone signaling has been demonstrated to be critical for the initiation and continuance of pregnancy. Through the induction of Ihh, Wnt, and Bmp pathways within the epithelial and stromal compartments of the uterus, embryo attachment and implantation occur followed by decidualization of the surrounding stroma. Furthermore, these pathways have been shown to be involved in uterine glandular development. This review highlights the integral role of uterine progesterone-mediated paracrine signaling in gland development and pregnancy.

► We describe the progesterone regulated paracrine signaling in early pregnancy.
► We discuss the affect of progesterone signaling on uterine gland development.
► The importance of the hedgehog pathway in early pregnancy is described.
► We propose a model for the inhibition of epithelial proliferation in implantation.