Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities.

TLDR

Progesterone is essential for pregnancy and has been implicated in various other reproductive processes, with its effects mediated by the progesterone receptor, which is often induced by estrogen. To define physiological events specifically attributable to progesterone in vivo, we generated a mouse model lacking the progesterone receptor. The PR‑null mouse was created by embryonic stem cell gene‑targeting techniques. PR‑null mice develop normally to adulthood, but adult females exhibit multiple reproductive defects—including failure to ovulate, uterine hyperplasia and inflammation, impaired mammary development, and lack of sexual behavior—demonstrating progesterone’s pleiotropic role.

Abstract

Although progesterone has been recognized as essential for the establishment and maintenance of pregnancy, this steroid hormone has been recently implicated to have a functional role in a number of other reproductive events. The physiological effects of progesterone are mediated by the progesterone receptor (PR), a member of the nuclear receptor superfamily of transcription factors. In most cases the PR is induced by estrogen, implying that many of the in vivo effects attributed to progesterone could also be the result of concomitantly administered estrogen. Therefore, to clearly define those physiological events that are specifically attributable to progesterone in vivo, we have generated a mouse model carrying a null mutation of the PR gene using embryonic stem cell/gene targeting techniques. Male and female embryos homozygous for the PR mutation developed normally to adulthood. However, the adult female PR mutant displayed significant defects in all reproductive tissues. These included an inability to ovulate, uterine hyperplasia and inflammation, severely limited mammary gland development, and an inability to exhibit sexual behavior. Collectively, these results provide direct support for progesterone's role as a pleiotropic coordinator of diverse reproductive events that together ensure species survival.