Rescue of preimplantatory egg development and embryo implantation in prolactin receptor-deficient mice after progesterone administration

PRL, a hormone secreted essentially by the pituitary and other extrapituita ry sources such as decidua, has been attributed regulatory roles in reprodu ction and cell growth in mammals. These effects are mediated by a membrane PRL receptor belonging to the cytokine receptor superfamily. Null mutation of the PRL receptor gene leads to female sterility due to a severely compro mised preimplantation development and a complete failure of the implantatio n of the few embryos reaching the blastocyst stage, strongly implicating PR L in the maternal control of implantation. We measured the hormonal status of -/- mice, which confirmed that the corpus luteum is unable to produce pr ogesterone. Progesterone administration to -/- mice completely rescued the development of preimplantatory eggs and embryo implantation. Pregnancy coul d be maintained to 19.5 days postcoitum, with about 22% of resulting embryo s reaching adulthood. Although progesterone and perhaps PRL appear to facil itate mouse preembryo development throughout the preimplantation stages, ot her factors as well as a possible direct effect of PRL on the uterus are pr obably necessary to fully maintain pregnancy. Finally, reduced ductal side- branching in the mammary gland can be rescued by progesterone treatment, bu t females exhibit reduced alveolar formation. Our model establishes the PRL receptor as a key regulator of reproduction and provides novel insights in to the function of lactogenic hormones and their receptor.