Implantation and decidualization defects in prolactin receptor (PRLR)-deficient mice are mediated by ovarian but not uterine PRLR

PRL and its homologs accomplish their biological effects through the PRL re ceptor (PRLR). We evaluated the expression and function of PRLR in the embr yo and uterus during the periimplantation period because PRLR deficiency re sults in implantation failure. In wild-type mice, PRLR expression was local ized to undecidualized stromal cells in the antimesometrial border on days 6-8 of pregnancy. A small population of PRLR-expressing cells was observed adjacent to the ectoplacental cone in the mesometrial stroma. Low levels of PRLR expression were also detected in the developing embryo on days 6-8. T o determine the significance of PRLR expression in this distribution, we ex amined implantation and decidualization in PRLR-/- mice. Progesterone (P-4) administration rescued infertility in PRLR-/- mice from the periimplantati on period to midgestation. Artificially induced decidualization was absent in pseudopregnant PRLR-/- mice but was identical to wild-type in P-4-treate d PRLR-/- mice. Furthermore, wildtype and P-4-treated PRLR-/- mice had simi lar expression of the implantation-specific genes, LIF, amphiregulin, HB-EG F, COX-1, COX-2, PPAR delta, Hoxa-10, cyclin-D3, VEGF, and its receptors, F lk-1 and neuropilin-1. Together, these results show that luteal P-4 product ion via ovarian PRLR signaling is required for implantation and early pregn ancy. The function of uterine PRLR remains unclear. However, the eventual l oss of pregnancy in P-4-treated PRLR-/- mice suggests that uterine PRLR may be essential for the support of late gestation.