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 extrapituitary sources such as decidua, has been attributed regulatory roles in reproduction 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 compromised preimplantation development and a complete failure of the implantation of the few embryos reaching the blastocyst stage, strongly implicating PRL in the maternal control of implantation. We measured the hormonal status of -/- mice, which confirmed that the corpus luteum is unable to produce progesterone. Progesterone administration to -/- mice completely rescued the development of preimplantatory eggs and embryo implantation. Pregnancy could be maintained to 19.5 days postcoitum, with about 22% of resulting embryos reaching adulthood. Although progesterone and perhaps PRL appear to facilitate mouse preembryo development throughout the preimplantation stages, other factors as well as a possible direct effect of PRL on the uterus are probably necessary to fully maintain pregnancy. Finally, reduced ductal side-branching in the mammary gland can be rescued by progesterone treatment, but females exhibit reduced alveolar formation. Our model establishes the PRL receptor as a key regulator of reproduction and provides novel insights into the function of lactogenic hormones and their receptor.
Binart
N
N
INSERM, U-344, Endocrinologie Moléculaire, Faculté de Médecine Necker, Paris, France. binart@necker.fr
Helloco
C
C
Ormandy
C J
CJ
Barra
J
J
Clément-Lacroix
P
P
Baran
N
N
Kelly
P A
PA
D000818:Animals; D010064:Embryo Implantation; D047108:Embryonic Development; D005260:Female; D006728:Hormones / Q000097:blood; D008321:Mammary Glands, Animal / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D010063:Ovum / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D011981:Receptors, Prolactin / Q000172:deficiency* / Q000235:genetics
D006728:Hormones; D011981:Receptors, Prolactin; D011374:Progesterone