Paternal age and its effects on sperm genetics and offspring health

Background: Advanced paternal age (APA) has become an increasingly relevant topic as sociocultural and economic factors contribute to delayed parenthood worldwide. While the impact of maternal age on reproductive outcomes is well established, the influence of paternal aging on sperm quality, genetic integrity, and offspring health has only recently gained significant attention. Objective: This narrative review aims to synthesize current evidence on the biological, clinical, and societal implications of APA, highlighting its effects on testicular function, sperm quality, reproductive outcomes, and offspring health, while also discussing future directions for prevention and intervention. Methods: A comprehensive literature search was conducted using PubMed, Cochrane Library, and Google Scholar, focusing on studies published between 2000 and 2024. Eligible sources include observational studies, systematic reviews, meta-analyses, and mechanistic research addressing paternal age, sperm quality, genetic and epigenetic alterations, and reproductive outcomes. Data were synthesized narratively to provide an integrative overview of the topic. Results: Evidence indicates that while sperm count remains relatively stable with age, sperm motility, morphology, and DNA integrity decline, largely due to oxidative stress, impaired DNA repair, and accumulation of de novo mutations. These alterations contribute to longer time-to-pregnancy, higher miscarriage rates, and increased need for assisted reproductive technologies. Furthermore, APA is associated with adverse offspring outcomes, including congenital anomalies, autism spectrum disorder, schizophrenia, and certain childhood cancers. Epigenetic modifications in sperm may play a key role in mediating intergenerational effects. Conclusion: APA represents a multifaceted challenge with biological, clinical, and public health implications. Lifestyle interventions, antioxidant therapy, advanced sperm selection techniques, and preimplantation genetic testing hold promise for mitigating risks, while emerging genomic and epigenomic tools may enable personalized reproductive counselling in the future. Greater awareness of APA, both in clinical practice and society, is essential to support informed reproductive decision-making and safeguard offspring health.