We used frogs to show that the effects of the anti-androgenic pesticide linuron extend beyond directly exposed males to their offspring and grand-offspring. Offspring displayed reduced fertility, impaired spermatogenesis, altered body weight, and metabolic disruption, providing the first evidence of transgenerational paternal epigenetic inheritance in amphibians. Follow-up work identified widespread DNA methylation changes in F2 brains, testes, and pancreas, affecting genes linked to growth, thyroid signaling, spermatogenesis, and metabolic regulation, as well as genes controlling the epigenetic machinery itself. These findings demonstrate that linuron induces heritable epigenetic alterations across multiple organs, with long-term effects on fertility, growth, and metabolism.
In parallel, we established a mouse model to study the transgenerational effects of adult male anti-androgen exposure. Exposed males showed hepatic stress, oxidative damage, and metabolic dysfunction, including features consistent with non-alcoholic fatty liver disease. They also developed persistent immunosuppression, with reduced leukocytes and T cells, expansion of immunosuppressive myeloid-derived suppressor cells, cytokine alterations, and evidence of oxidative stress–driven lymphocyte arrest. Follow-up work revealed profound microbiome disruption, suggesting interactions between gut bacteria and immune impairment. Importantly, dose-dependent epigenetic changes in sperm were also observed, and offspring of exposed males displayed similar metabolic and immune alterations, many persisting into the F2 generation, demonstrating transgenerational inheritance.
Together, these cross-species studies provide strong evidence that anti-androgenic pollutants directly impair male reproductive, metabolic, hepatic, and immune health, and induce heritable epigenetic alterations across generations. The results link molecular changes in sperm, brain, testis, pancreas, liver, and immune system to long-term effects on fertility, growth, metabolism, and immunity, with broad implications for both ecology and human health. We have disseminated our findings through peer-reviewed publications, international conferences, TV and radio news, and press releases, ensuring broad visibility among scientists, policymakers, and the public. Moving forward, we will continue to share outcomes from our unpublished studies through publications, media outreach, and stakeholder engagement, maximizing their scientific, societal, and regulatory impact.
