The G→ C polymorphism of the p53 gene impairs pregnancy rates and endometrial LIF production in humans

Abstract

OBJECTIVE: p53 has recently been shown to regulate LIF production in the murine model.A polymorphism of the p53 gene at codon 72 (Arg→Pro) decreases p53 activity and litter size.We hypothesize that women who carry the variant p53c72 polymorphism may experience decreased implantation and pregnancy rates via decreased LIF production.In order to support the effect of p53 activity on LIF production in humans,endometrial biopsy slides in women homozygous for the variant allele were stained for LIF. DESIGN: Prospective analysis of oocyte donor recipients.IVF outcome of the group carrying the p53c72 Pro(variant) polymorphism compared to p53c72 Arg(wild type) was assessed. MATERIALS AND METHODS: A total of one hundred and thirty whole blood samples were collected from donor egg recipients (DER).DNA was extracted and Taqman PCR amplification was performed. Endometrial biopsies were collected prior to the recipient transfer cycle.Immunolabelling and optical density for tissue stained for LIF was measured and compared to donor egg recipients homozygous for the wild type allele.This is on a scale of strong staining =3, and no staining = 0. RESULTS: There was a trend towards decreased implantation rates (35% vs. 50%) and pregnancy rates (57% vs. 75%) for patients with the variant polymorphism compared to the wild type, respectively (p=0.08).Tissue staining of endometrial biopsy slides for LIF showed decreased optical density in patients homozygous for the variant polymorphism compared to wild type donor egg recipients(1.2 vs. 2.3, respectively). CONCLUSIONS: We have found that women who are homozygous for the p53c72Pro variant have decreased LIF production at the level of the endometrium compared to wild type controls.Although there was a trend towards decreased implantation and pregnancy rates in recipients homozygous for the variant allele,the lack of significance suggests that other cytokines may help overcome any negative impact of this polymorphism at the level of the endometrium despite decreased LIF production.