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.

中文翻译：

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脱氧雪腐镰刀菌烯醇通过刺激大鼠线粒体裂变抑制间质祖细胞发育

脱氧雪腐镰刀菌烯醇 (DON) 是一种常见的食品污染物，会损害男性生殖功能。本研究调查了 DON 暴露对青春期前雄性大鼠 Leydig 祖细胞 (PLC) 发育的影响和机制。从出生后 21-28 天开始，给大鼠口服 DON（0-4 mg/kg）。 DON 增加 PLC 增殖，但抑制 PLC 成熟和功能，包括降低睾酮水平并下调 HSD11B1 和 INSL3 等生物标志物（≥2 mg/kg）。 DON 还通过上调 DRP1 和 FIS1 蛋白水平刺激线粒体裂变，并通过降低体内 PLC 的抗氧化能力（包括 NRF2、SOD1、SOD2 和 CAT）来增加氧化应激。在体外，DON (2–4 μM) 抑制 PLC 雄激素生物合成，增加活性氧的产生和 DRP1、FIS1、MFF 和 pAMPK 的蛋白水平，降低线粒体膜电位和 MFN1 蛋白水平，并导致线粒体断裂。线粒体裂变抑制剂 mdivi-1 可减轻 DON 引起的 PLC 损伤。 DON 抑制 PLC 类固醇生成，增加氧化应激，扰乱线粒体稳态，并损害成熟。总之，DON 通过刺激线粒体裂变破坏青春期前大鼠的 PLC 发育。