轉(zhuǎn)錄因子p53作為一種腫瘤抑制因子已經(jīng)受到廣泛研究,，但人們對(duì)其正常生理作用卻知之甚少?，F(xiàn)在,，用小鼠所做的一項(xiàng)研究將p53的正常功能與繁殖和生育聯(lián)系了起來,。p53缺乏導(dǎo)致雌性小鼠胚胎著床較差,、受孕率較低和后代身材較小,。p53是通過調(diào)控LIF來發(fā)揮這一功能的,。 LIF是一種細(xì)胞因子，參與囊胚的著床,。這項(xiàng)工作讓我們看到這樣一個(gè)可能性：p53的正常功能對(duì)于著床的成功很重要,，尤其是對(duì)經(jīng)歷體外授精或胚胎轉(zhuǎn)移的婦女來說；同時(shí)這一結(jié)果也讓我們看到了提高習(xí)慣性著床失敗婦女的著床效率的一個(gè)潛在策略,。
原始出處:
Nature 450, 721-724 (29 November 2007) | doi:10.1038/nature05993; Received 24 July 2007; Accepted 10 October 2007
p53 regulates maternal reproduction through LIF
Wenwei Hu1,3, Zhaohui Feng1,3, Angelika K. Teresky1 & Arnold J. Levine1,2
Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey 08903, USA
The Simons Center for Systems Biology, The Institute for Advanced Study, Princeton, New Jersey 08540, USA
These authors contributed equally to this work.
Correspondence to: Arnold J. Levine1,2 Correspondence and requests for materials should be addressed to A.J.L. (Email: [email protected]).
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.
