Li Bo, Huo Siming, Du Jiayu, Zhang Xuliang, Zhang Jian, Song Miao, Li Yanfei
Key Laboratory of the Provincial Education, Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Key Laboratory of the Provincial Education, Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Environ Pollut. 2025 Feb 15;367:125546. doi: 10.1016/j.envpol.2024.125546. Epub 2024 Dec 20.
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.
双酚F（BPF）是一种环境内分泌干扰物，能够穿过胎盘屏障并影响后代的生长发育。尽管其具有潜在影响，但关于BPF对雄性后代生殖功能影响的系统性研究仍然有限。在本研究中，分别在妊娠期和哺乳期将怀孕的雌性小鼠暴露于40、400和4000μg/kg剂量的BPF中，以评估其对雄性后代（F1代）睾丸损伤、睾酮水平和精子发生的影响，并使用转录组学进一步探索其机制。首先，研究表明BPF可诱导F1代小鼠睾丸损伤，导致睾酮水平和精子质量下降。其次，转录组分析显示BPF通过破坏视黄醇代谢影响F1代小鼠的精子发生。第三，转录组分析显示BPF通过将睾酮前体脱氢表雄酮（DHEA）转向16α-羟基脱氢表雄酮而非睾酮的合成，降低F1代小鼠的睾酮合成能力。最后，证实BPF通过抑制cAMP信号通路阻碍胆固醇向线粒体的转运，从而影响睾酮合成。总之，本研究结果表明，孕期暴露于BPF可导致F1代雄性小鼠生殖功能障碍。
