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The nuclear receptor co-repressor Nrip1 (RIP140) is essential for female fertility

Nature Medicine volume 6, pages 1368–1374 (2000)Cite this article

Abstract

Ovulatory dysfunction is the commonest cause of female infertility. Here we show that the co-repressor nuclear-receptor-interacting protein 1 (Nrip1; encoded by the gene Nrip1) is essential for ovulation. Mice null for this protein are viable, but female mice are infertile because of complete failure of mature follicles to release the oocyte at ovulation. In contrast, luteinization proceeds normally, resulting in a phenotype closely resembling that of luteinized unruptured follicle syndrome, often associated with infertility in women. Therefore, whereas the pre-ovulatory surge of luteinizing hormone induces both ovulation and luteinization, the ability to suppress the action of nuclear receptors is essential for the coordinated control of ovarian function with the essential process of oocyte release dependent on the activity of the transcriptional co-repressor Nrip1 (RIP40).

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Figure 1: Targeted inactivation of mouse Nrip1.
Figure 2: RIPKO mice are reduced in size and females are infertile.
Figure 3: Anovulatory phenotype of RIPKO mice.
Figure 4: The endocrine function of RIPKO ovaries is normal.
Figure 5: Expression of Nrip1 in RIPKO, heterozygous and wild-type mice.
Figure 6: mRNA expression of ovarian marker genes in gonadotrophin-treated wild-type and RIPKO mice.

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Acknowledgements

We thank P. Hagger, T. Crafton and the staff in Biological Resources; V. Pocock for analysis of ovarian sections; and R. Poulsom, R. Jeffrey and J. Longcroft for in situ hybridization studies, with G. Elia and the staff of the histopathology unit. Oligonucleotides were synthesized by I. Goldsmith. We thank R. Winston, D. Shima and H. Macneil, as well as members of the Molecular Endocrinology Laboratory, for advice and comments on the manuscript.

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  1. Roger White, Göran Leonardsson & Malcolm Parker

    Present address: Institute of Reproductive and Developmental Biology, Imperial College School of Medicine, Hammersmith Hospital, London, W12 ONN, UK

Authors and Affiliations

  1. Imperial Cancer Research Fund, Molecular Endocrinology Laboratory, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK

    Roger White, Göran Leonardsson & Malcolm Parker

  2. Imperial Cancer Research Fund, Clare Hall Laboratories, Blanche Lane, South Mimms, Potters Bar, Herts, EN6 3LD, UK

    Ian Rosewell & Mary Ann Jacobs

  3. School of Biomedical Sciences, Kings College London, Guy's Campus, London Bridge, London, SE1 1UL, UK

    Stuart Milligan

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Correspondence to Malcolm Parker.

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White, R., Leonardsson, G., Rosewell, I. et al. The nuclear receptor co-repressor Nrip1 (RIP140) is essential for female fertility. Nat Med 6, 1368–1374 (2000). https://doi.org/10.1038/82183

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