Plastic-Associated Pollutants and the Paternal Germline: From Reproductive Toxicity and Sperm Molecular Alterations to Potential Offspring Effects

Paternal preconception health is increasingly recognized as an important determinant of reproductive success and offspring development. Plastic-associated contaminants, including endocrine-disrupting chemicals, microplastics, and nanoplastics, have been increasingly associated with adverse effects on male reproductive function. The effects of these exposures may extend beyond conventional sperm quality, potentially inducing molecular changes in paternal germ cells with consequences for embryonic development and offspring health. This review examines how preconception exposure to plastic-associated pollutants may alter the male germline through oxidative stress, mitochondrial dysfunction, endocrine disruption, inflammation, and epigenetic alterations. Particular attention is given to DNA methylation, histone modifications, non-coding RNAs, and other epigenetic mechanisms that may contribute environmentally induced molecular information to the embryo. We will provide information about experimental and epidemiological research related to environmental exposure in males and the resulting impacts on fertility, development of embryos, placenta function, adverse pregnancy outcomes, and vulnerability of the offspring to reproduction, metabolic, neurodevelopmental, and cardiovascular diseases. By integrating evidence from reproductive biology, toxicology, developmental epigenetics, and environmental health, this review provides a framework for understanding how environmental exposures may alter the paternal germline and potentially influence health across generations. Finally, we identify key research gaps and methodological challenges, outline priorities for future research, and emphasize the need for comprehensive exposure assessment, mechanistic studies in humans, and strategies to reduce environmental exposures during the preconception period.