P53 regulates maternal reproduction through lif

ABSTRACT Extensive studies have shown that p53 is important in tumour prevention1. However, little is known about its normal physiological function. Here we show that p53 is important in

reproduction, in a gender-specific manner. Significant decreases in embryonic implantation, pregnancy rate and litter size were observed in matings with _p53_-/- female mice but not with

_p53_-/- male mice. The gene encoding leukaemia inhibitory factor (LIF), a cytokine critical for implantation2, was identified as a p53-regulated gene that functions as the downstream

mediator of this effect. p53 can regulate both basal and inducible transcription of LIF. Loss of p53 decreased both the level and function of LIF in uteri. Lower LIF levels were observed in

the uteri of _p53_-/- mice than in those of _p53_+/+ mice, particularly at day 4 of pregnancy, when transiently induced high levels of LIF were crucial for embryonic implantation. This

observation probably accounts for the impaired implantation of embryos in _p53_-/- female mice. Administration of LIF to pregnant _p53_-/- mice restored maternal reproduction by improving

implantation. These results demonstrate a function for p53 in maternal reproduction through the regulation of LIF. Evidence is accumulating that p53 may have a similar function in humans.

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support SIMILAR CONTENT BEING VIEWED BY OTHERS CORE BINDING FACTORS ARE ESSENTIAL FOR OVULATION, LUTEINIZATION, AND FEMALE FERTILITY IN MICE Article Open access 18 June 2020 TOLL-LIKE

RECEPTOR-4 NULL MUTATION CAUSES FETAL LOSS AND FETAL GROWTH RESTRICTION ASSOCIATED WITH IMPAIRED MATERNAL IMMUNE TOLERANCE IN MICE Article Open access 16 August 2021 UTERINE EPITHELIAL GP130

ORCHESTRATES HORMONE RESPONSE AND EPITHELIAL REMODELING FOR SUCCESSFUL EMBRYO ATTACHMENT IN MICE Article Open access 16 January 2023 REFERENCES * Vogelstein, B., Lane, D. & Levine, A.

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references ACKNOWLEDGEMENTS We thank S. Christen for critical review of the manuscript, and I. Snyder and the staff of the University of Medicine and Dentistry of New Jersey animal facility

for providing animal care. This research was supported by grants from the Breast Cancer Research Foundation and the National Cancer Institute. AUTHOR CONTRIBUTIONS W.H., Z.F. and A.J.L.

designed the research. W.H., Z.F. and A.K.T. performed the research. W.H., Z.F. and A.J.L. analysed data and wrote the paper. AUTHOR INFORMATION Author notes * Wenwei Hu and Zhaohui Feng:

These authors contributed equally to this work. AUTHORS AND AFFILIATIONS * Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey

08903, USA , Wenwei Hu, Zhaohui Feng, Angelika K. Teresky & Arnold J. Levine * The Simons Center for Systems Biology, The Institute for Advanced Study, Princeton, New Jersey 08540, USA ,

Arnold J. Levine Authors * Wenwei Hu View author publications You can also search for this author inPubMed Google Scholar * Zhaohui Feng View author publications You can also search for

this author inPubMed Google Scholar * Angelika K. Teresky View author publications You can also search for this author inPubMed Google Scholar * Arnold J. Levine View author publications You

can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Arnold J. Levine. SUPPLEMENTARY INFORMATION SUPPLEMENTARY FIGURES This file contains

Supplementary Figures S1-S5 with Legends. (PDF 1115 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Hu, W., Feng, Z., Teresky, A. _et al._ p53

regulates maternal reproduction through LIF. _Nature_ 450, 721–724 (2007). https://doi.org/10.1038/nature05993 Download citation * Received: 24 July 2007 * Accepted: 10 October 2007 *

Published: 29 November 2007 * Issue Date: 29 November 2007 * DOI: https://doi.org/10.1038/nature05993 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this

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