The TP53 gene, first described in 1979, was identified as a tumor suppressor 
gene in 1989, when it became clear that its product, the p53 nuclear 
phosphoprotein, was frequently inactivated in many different forms of cancers. 
Nicknamed "guardian of the genome", TP53 occupies a central node in stress 
response networks. The p53 protein has a key role as transcription factor in 
limiting oncogenesis through several growth suppressive functions, such as 
initiating apoptosis, senescence, or cell cycle arrest. The p53 protein is 
directly inactivated in about 50% of all tumors as a result of somatic gene 
mutations or deletions, and over 80% of tumors demonstrate dysfunctional p53 
signaling. Beyond the undeniable importance of p53 as a tumor suppressor, an 
increasing number of new functions for p53 have been reported, including its 
ability to regulate energy metabolism, to control autophagy, and to participate 
in various aspects of differentiation and development. Recently, studies on 
genetic variations in TP53 among different populations have led to the notion 
that the p53 protein might play an important role in regulating fertility. This 
review summarizes current knowledge on the basic functions of different genes of 
the TP53 family and TP53 pathway with respect to fertility. We also provide 
original analyses based on genomic and genotype databases, providing further 
insights into the possible roles of the TP53 pathway in human reproduction.