Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
J Agric Food Chem. 2024 May 8;72(18):10616-10626. doi: 10.1021/acs.jafc.4c01151. Epub 2024 Apr 24.
Deoxynivalenol (DON) is a common food contaminant that can impair male reproductive function. This study investigated the effects and mechanisms of DON exposure on progenitor Leydig cell (PLC) development in prepubertal male rats. Rats were orally administrated DON (0-4 mg/kg) from postnatal days 21-28. DON increased PLC proliferation but inhibited PLC maturation and function, including reducing testosterone levels and downregulating biomarkers like HSD11B1 and INSL3 at ≥2 mg/kg. DON also stimulated mitochondrial fission via upregulating DRP1 and FIS1 protein levels and increased oxidative stress by reducing antioxidant capacity (including NRF2, SOD1, SOD2, and CAT) in PLCs in vivo. In vitro, DON (2-4 μM) inhibited PLC androgen biosynthesis, increased reactive oxygen species production and protein levels of DRP1, FIS1, MFF, and pAMPK, decreased mitochondrial membrane potential and MFN1 protein levels, and caused mitochondrial fragmentation. The mitochondrial fission inhibitor mdivi-1 attenuated DON-induced impairments in PLCs. DON inhibited PLC steroidogenesis, increased oxidative stress, perturbed mitochondrial homeostasis, and impaired maturation. In conclusion, DON disrupts PLC development in prepubertal rats by stimulating mitochondrial fission.
脱氧雪腐镰刀菌烯醇（DON）是一种常见的食物污染物，可损害男性生殖功能。本研究探讨了 DON 暴露对未成年雄性大鼠祖细胞莱迪希细胞（PLC）发育的影响及其机制。大鼠从出生后第 21 天至第 28 天经口给予 DON（0-4mg/kg）。DON 增加 PLC 增殖，但抑制 PLC 成熟和功能，包括在≥2mg/kg 时降低睾酮水平和下调 HSD11B1 和 INSL3 等生物标志物。DON 还通过上调 DRP1 和 FIS1 蛋白水平刺激线粒体分裂，并通过降低 PLC 中的抗氧化能力（包括 NRF2、SOD1、SOD2 和 CAT）增加氧化应激。在体外，DON（2-4μM）抑制 PLC 雄激素生物合成，增加活性氧产生和 DRP1、FIS1、MFF 和 pAMPK 蛋白水平，降低线粒体膜电位和 MFN1 蛋白水平，并导致线粒体碎片化。线粒体分裂抑制剂 mdivi-1 减轻了 DON 诱导的 PLC 损伤。DON 抑制 PLC 类固醇生成，增加氧化应激，扰乱线粒体动态平衡，并损害成熟。总之，DON 通过刺激线粒体分裂破坏未成年大鼠 PLC 的发育。
