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Endocrinology Vol. 141, No. 7 2691-2697
Copyright © 2000 by The Endocrine Society

ARTICLES

Rescue of Preimplantatory Egg Development and Embryo Implantation in Prolactin Receptor-Deficient Mice after Progesterone Administration

Nadine Binart, Christine Helloco, Christopher J. Ormandy, Jacqueline Barra, Philippe Clément-Lacroix, Nathalie Baran and Paul A. Kelly

INSERM, U-344, Endocrinologie Moléculaire, Faculté de Médecine Necker (N.B., C.H., P.C.-L., N.B.), 75730 Paris, France; Cancer Research Program, Garvan Institute of Medical Research (C.J.O.), Darlinghurst, New South Wales 2010, Sydney, Australia; and Unité de Biologie du Développement, Institut Pasteur (J.B.), Paris 75015, France

Address all correspondence and requests for reprints to: Dr. Nadine Binart, INSERM, U-344, Endocrinologie Moléculaire, Faculté de Médecine Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France. E-mail: binart{at}necker.fr

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.




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