p53家族及其通路相关蛋白调节母性生殖的新功能

The new function of p53 family and its pathway related proteins in female reproduction

p53是一种重要的抗癌基因,同时它也是机体感受环境压力并进行相应调节的关键基因之一。最近的研究发现东亚人群p53 Arg72Pro受到冬季温度自然选择,表明p53可能在生殖中发挥作用。同时,p53及其通路中的癌基因鼠双微体2(Murinedoubleminute2,Mdm2)、MdmX和Hausp(Herpesvirus-associated ubiquitin-specific protease)基因的单核苷酸多态性(Single nucleotide polymorphisms,SNP)与女性生殖疾病易感性相关。P53蛋白通过其DNA结合区(DNA-binding domain,DBD)调控白血病抑制因子(Leukaemiainhibitory factor,LIF)表达,从而影响胚胎植入过程,实现其在母性生殖中的作用。p53通路中Mdm2、MdmX和Hausp可以调控P53蛋白的表达水平和活性,同时还可以在胚胎植入时准确的调控p53的表达水平,促进胚胎植入;P53家族成员P63、P73具有P53相似的DBD区,但P63和P73是通过别的途径影响到母性生殖;在卵母细胞受到射线或者化学损伤后,P63能促进其凋亡,减少畸型的产生;P73能影响纺锤体复合物的组装,而纺锤体复合物缺失将导致胚泡质量低下,微管结合的动粒缺失和细胞非整倍性的增加。文章主要综述了p53家族、p53通路中的相关蛋白对母性生殖的影响,为提高IVF-ET成功指出了新方法,同时也为不明原因的不孕患者提供了新的诊断思路,将有助于制定合理的个性化治疗不孕方案。

p53 is an important tumor suppressor gene andone of the key genes in sensing and regulating responses to the environmental stress.Recent study showed that cold winter temperature naturally selectedp53 Arg72 in eastern Asian population,suggestingthat p53 playsa role in reproduction.It has also been reported that some SNPs of p53,Mdm2（Murine double minute 2）,MdmX and Hausp（Herpes virus-associated ubiquitin-specific protease） in p53 pathway are associated with the risk of the women’s reproduction disorder.p53 regulates the LIF（leukaemia inhibitory factor） expression level by its DBD domain,and thus contributes to female reproduction by affecting the embryo implantation process.The MDM2,MDMX,and HAUSP proteins regulatesthelevel and activity of p53 protein,which are critical for the appropriate p53 response in the embryo implantation process.The members of p53 family,p63 and p73,also play roles in female reproduction through other pathways.p63 has been implicated as a major regulator of oocyte death following treatment with irradiation and chemotherapeutic drugs,which prevents fetal malformation.p73 regulates the formation of spindle assembly complex（SAC）.The dysfunction of SAC results in poor blastocyst quality and defects in kinetochore–microtubule associations,which leads to aneuploidy.This review summarized the function of p53 family and its pathway related proteins in female reproduction,pointed out a new method in improving the success rate in IVF-ET,and provided a new diagnosis idea for unexplainedinfertile women.It will facilitate personalized strategies in the infertility therapy