title: Regulation of female reproduction by p53 and its family members.
abstract: 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.
authors.affiliation: Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey, USA.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Feng
authors.forename: Cen
authors.initials: C
authors.lastname: Zhang
authors.forename: Hey-Joo
authors.initials: HJ
authors.lastname: Kang
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Sun
authors.forename: Haijian
authors.initials: H
authors.lastname: Wang
authors.forename: Asad
authors.initials: A
authors.lastname: Naqvi
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Frank
authors.forename: Zev
authors.initials: Z
authors.lastname: Rosenwaks
authors.forename: Maureen E
authors.initials: ME
authors.lastname: Murphy
authors.forename: Arnold J
authors.initials: AJ
authors.lastname: Levine
authors.forename: Wenwei
authors.initials: W
authors.lastname: Hu
mesh_terms: D000328:Adult; D000483:Alleles; D000818:Animals; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D010064:Embryo Implantation / Q000235:genetics; D004717:Endometrium / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007247:Infertility, Female / Q000235:genetics; D053605:Leukemia Inhibitory Factor / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012098:Reproduction / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D053605:Leukemia Inhibitory Factor; D009687:Nuclear Proteins; C115051:TP63 protein, human; C000606460:TP73 protein, human; D014157:Transcription Factors; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins