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Embryo Transfer Experiments and Ovarian Transplantation Identify the Ovary as the Only Site in Which Nuclear Receptor Interacting Protein 1/RIP140 Action Is Crucial for Female Fertility

Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College (G.L., R.W., M.P.), London, United Kingdom W12 1ONN; Imperial Cancer Research Fund, Clare Hall Laboratories (M.A.J.), South Mimms, Potters Bar, United Kingdom EN6 3LD; Imperial Cancer Research Fund, In Situ Hybridization Service (R.J., R.P.), London, United Kingdom WC2A 3PX; and School of Biomedical Sciences, Kings College London, Guy’s Campus (S.M.), London, United Kingdom SE1 1UL

Address all correspondence and requests for reprints to: Dr. Malcolm Parker, Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College, Du Cane Road, London, United Kingdom W12 ONN. E-mail: m.parker{at}ic.ac.uk

Spatial and temporal regulation of gene expression by a number of different nuclear receptors is critical in female reproduction. In this study we investigated whether the nuclear receptor corepressor nuclear receptor interacting protein 1 (Nrip1)/RIP140, which is essential for ovulation, is also required for postovulatory events, leading to pregnancy and parturition. Expression analysis indicated that Nrip1 is present in the uterus in stromal and glandular epithelial cells, primary decidual cells, and subsequently in differentiating decidual cells at the anti-mesometrial side of the implantation site. It also indicated a temporal regulation of Nrip1 in the corpora lutea at different stages of pregnancy, with increased levels at midgestation at approximately d 9.5 postcoitum (pc). By performing both embryo and ovarian transfer experiments we demonstrate that, provided the block to ovulation is by-passed, Nrip1^-/- mice are capable of establishing and maintaining pregnancies. However, although the majority of offspring derived from ovarian transplantation survived, approximately 50% of embryos were resorbed by d 13.5 pc after embryo transfer, and the majority of pups were stillborn or died soon thereafter. Thus, although Nrip1 is differentially expressed in the reproductive tract, we conclude that the ovary is the only site in which its action is essential for fertility, with a crucial role in ovulation and a secondary role in the maintenance of pregnancy.

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