Effect of bisphenol F on reproductive function in F1 generation male mice and its potential mechanisms

Bisphenol F (BPF) is an environmental endocrine disruptor capable of crossing the placental barrier and affecting the growth and development of offspring. Despite its potential impact, systematic research about effects of BPF on the reproductive function of male offspring remains limited. In this study, pregnant female mice were exposed to BPF at doses of 40, 400, and 4000 μg/kg during gestation and lactation, respectively, to evaluate its impact on testicular damage, testosterone levels, and spermatogenesis of male offspring (F1 generation), and further explore the mechanisms using transcriptomics. First, the study demonstrated that BPF induces testicular damage in F1 generation mice, leading to decreased testosterone levels and sperm quality. Second, transcriptomic analysis revealed that BPF affected spermatogenesis in F1 generation mice by disrupting retinol metabolism. Third, transcriptomic analysis revealed that BPF reduce the capacity for testosterone synthesis in F1 generation mice by diverting the testosterone precursor dehydroepiandrosterone (DHEA) towards the synthesis of 16α-hydroxydehydroepiandrosterone rather than testosterone. Finally, it was confirmed that BPF hinder cholesterol transport to mitochondria by inhibiting the cAMP signaling pathway, thereby impacting testosterone synthesis. In summary, the results of this study suggest that gestational exposure to BPF can lead to reproductive dysfunction in F1 generation male mice.