Current declines in male reproductive health may, in part, be driven by anthropogenic environmental chemical (EC) exposure. Using a biosolids treated pasture (BTP) sheep model, this study examined the effects of gestational exposure to a translationally relevant EC mixture. Testes of 8-week-old ram lambs from mothers exposed to BTP during pregnancy contained fewer germ cells and had a greater proportion of Sertoli-cell-only seminiferous tubules. This concurs with previous published data from fetuses and neonatal lambs from mothers exposed to BTP. Comparison between the testicular transcriptome of biosolids lambs and human testicular dysgenesis syndrome (TDS) patients indicated common changes in genes involved in apoptotic and mTOR signalling. Gene expression data and immunohistochemistry indicated increased HIF1α activation and nuclear localisation in Leydig cells of BTP exposed animals. As HIF1α is reported to disrupt testosterone synthesis, these results provide a potential mechanism for the pathogenesis of this testicular phenotype, and TDS in humans.

目前男性生殖健康的下降可能部分是由人为环境化学品 (EC) 暴露引起的。本研究使用生物固体处理过的牧场 (BTP) 绵羊模型，检查了妊娠期接触转化相关的 EC 混合物的影响。来自怀孕期间暴露于 BTP 的母亲的 8 周大公羊羔羊的睾丸含有较少的生殖细胞，并且具有更大比例的仅支持细胞的曲细精管。这与之前公布的来自暴露于 BTP 的母亲的胎儿和新生羔羊的数据一致。biosolids 羔羊和人类睾丸发育不全综合征 (TDS) 患者的睾丸转录组之间的比较表明，参与细胞凋亡和 mTOR 信号传导的基因存在共同变化。基因表达数据和免疫组织化学表明 BTP 暴露动物的 Leydig 细胞中 HIF1α 激活和核定位增加。据报道，HIF1α 会破坏睾酮合成，这些结果为这种睾丸表型和人类 TDS 的发病机制提供了潜在机制。