Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey, USA.
FASEB J. 2011 Jul;25(7):2245-55. doi: 10.1096/fj.10-180166. Epub 2011 Mar 14.
Tumor suppressor p53 is crucial for embryonic implantation through transcriptional up-regulation of uterine leukemia inhibitory factor (LIF). This article reports that p53 and estrogen receptor α were activated in endometrial tissues during implantation to coordinately regulate LIF production. By using human p53 knockin (Hupki) mice carrying a single nucleotide polymorphism (SNP) at codon 72 (arginine/proline), the arginine allele was demonstrated to produce higher uterine LIF levels during implantation than the proline allele. In humans, the diversity of haplotypes of the p53 gene has decreased during evolution, because the arginine allele, existing in only a subset of haplotypes, is under positive selection. This observation is consistent with previous results showing that the proline allele is enriched in patients undergoing in vitro fertilization (IVF). Studies with p63- and p73-knockout mice have demonstrated the involvement of p63 and p73 in female reproduction and their roles in egg formation and apoptosis (p63) and spindle checkpoint (p73) in female mice. Here, the role of p63 and p73 in human reproduction was investigated. Selected alleles of SNPs in p63 and p73 genes were enriched in IVF patients. These findings demonstrate that the p53 family members are involved in several steps to regulate female reproduction in mice and humans.
肿瘤抑制因子 p53 通过转录上调子宫白血病抑制因子（LIF）对于胚胎着床至关重要。本文报道 p53 和雌激素受体α 在着床期间在内膜组织中被激活，以协调调节 LIF 的产生。通过使用在密码子 72 处携带单核苷酸多态性（SNP）的人 p53 敲入（Hupki）小鼠（精氨酸/脯氨酸），证明精氨酸等位基因在着床期间比脯氨酸等位基因产生更高的子宫 LIF 水平。在人类中，p53 基因的单倍型多样性在进化过程中减少了，因为仅存在于一部分单倍型中的精氨酸等位基因受到正选择。这一观察结果与先前的结果一致，即脯氨酸等位基因在接受体外受精（IVF）的患者中更为丰富。p63 和 p73 敲除小鼠的研究表明，p63 和 p73 参与女性生殖，其在卵子形成和凋亡（p63）和纺锤体检查点（p73）中发挥作用在雌性小鼠中。在这里，研究了 p63 和 p73 在人类生殖中的作用。p63 和 p73 基因中 SNP 的选定等位基因在 IVF 患者中富集。这些发现表明，p53 家族成员参与调节小鼠和人类的多个步骤来调节女性生殖。
