How contemporary human reproductive behaviours influence the role of fertility-related genes: the example of the P53 gene.

Recently numerous polymorphic fertility genes have been associated with reproductive system diseases causing infertility/subfertility. nvestigations carried out in populations at natural fertility suggest that some fertility genes have acquired clinical relevance only in the last decades due to the interaction with contemporary reproductive behaviours (birth control, delayed childbearing, and spacing birth order among others). In recent years, a new physiological role in human fertility regulation has emerged for the tumor suppressor p53 gene (P53), and the P53 Arg72Pro polymorphism has been associated with recurrent implantation failure in humans. In order to detect a possible interaction between fertility gene P53 and reproductive patterns, in present investigation we examined the impact of Arg72Pro polymorphism on fertility in two samples of Italian women collected from populations with different (premodern and modern) reproductive behaviours, not selected for impaired fertility. Among the women at near-natural fertility(n=98), the P53 genotypes were not associated with different reproductive efficiency, whereas among those with modern reproductive behaviours (n=68), the P53 genotypes were associated with different mean numbers of children (Pro/Pro <Pro/Arg <Arg/Arg, =0.056) and a significant negative relationship between the number of children and P53 Pro allele frequencies (p=0.028) was observed. These results are consistent with those of clinical studies reporting an association between the P53 Pro allele and recurrent implantation failure. These findings seem to support the hypothesis that some common variants of fertility genes may have become “detrimental” following exposure to modern reproductive patterns and might t therefore be associated with reduced reproductive success.