Male infertility may be an early clinical manifestation of systemic genomic instability due to shared biological pathways, such as Y-chromosome microdeletions (AZF regions), germline DNA repair defects, mutations in tumor suppressor genes (e.g., BRCA1/2, TP53), mismatch repair gene mutations (e.g., MLH1, MSH2), and dysregulated epigenetic profiles. Here, TP53 is linked to male infertility.