Abstract：
Microplastics (MPs) pollution poses a global environmental challenge with significant concerns regarding its potential impact on human health. Toxicological investigations have revealed multi-system impairments caused by MPs in various organisms. However, the specific reproductive hazards in human contexts remain elusive, and understanding the transgenerational reproductive toxicity of MPs remains limited. This study delves into the reproductive toxicity resulting from lactational exposure to polystyrene MPs (PS-MPs) in female mice, extending the inquiry to assess the reproductive effects on their offspring bred by rigorous natural mating. The MPs dosage corresponds to the detected concentration in infant formula prepared using plastic bottles. By systematically evaluating the reproductive phenotypes of F0 female mice from birth to adulthood, we found that female mice exposed to PS-MPs exhibited delayed puberty, disturbed estrous cyclicity, diminished fertility, elevated testosterone, abnormal follicle development, disrupted ovarian steroidogenesis, and ovarian inflammation. Importantly, the observed inheritable reproductive toxicity manifested with gender specificity, showcasing more pronounced abnormalities in male offspring. Specifically, reproductive disorders did not manifest in female offspring; however, a significant decrease in sperm count and viability was observed in PS-MPs-exposed F1 males. Testicular transcriptomics analysis of F1 males significantly enriched pathways associated with reproductive system development and epigenetic modification, such as male germ cell proliferation, DNA methylation, and histone modification. In summary, real-life exposure to PS-MPs impaired the reproductive function of female mice and threateningly disrupted the spermatogenesis of their F1 male offspring, which raises serious concerns about inter- and trans-generational reproductive toxicities of MPs in mammals. These findings underscore the potential threats of MPs to human reproductive health, emphasizing the need for continued vigilance and research in this critical area.
摘要：
微塑料（MP）污染对全球环境构成挑战，对其对人类健康的潜在影响存在重大担忧。毒理学研究表明，各种生物中的MPs会引起多系统损伤。然而,人类环境中特定的生殖危害仍然难以捉摸，和理解MPs的跨代生殖毒性仍然有限。本研究探讨了雌性小鼠哺乳期暴露于聚苯乙烯MPs（PS-MPs）的生殖毒性，扩大调查范围，以评估严格自然交配对其后代的生殖影响。MP剂量对应于使用塑料瓶制备的婴儿配方中的检测浓度。通过系统评价F0雌性小鼠从出生到成年的生殖表型,我们发现暴露于PS-MPs的雌性小鼠表现出青春期延迟，受扰的动情周期，生育率下降,睾酮升高,卵泡发育异常,卵巢类固醇生成中断，和卵巢炎症。重要的是,观察到的可遗传生殖毒性表现为性别特异性，在雄性后代中显示出更明显的异常。具体来说,生殖障碍在雌性后代中没有表现；然而，在暴露于PS-MPs的F1男性中观察到精子数量和活力显著下降.F1雄性的睾丸转录组学分析显着丰富了与生殖系统发育和表观遗传修饰相关的途径，如男性生殖细胞增殖，DNA甲基化，和组蛋白修饰。总之,现实生活中暴露于PS-MPs会损害雌性小鼠的生殖功能，并威胁破坏其F1雄性后代的精子发生，这引起了对哺乳动物中MP的代际和跨代生殖毒性的严重关注。这些发现强调了国会议员对人类生殖健康的潜在威胁，强调需要在这一关键领域继续保持警惕和研究。
