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<p>Male infertility has been increasing globally, raising concerns for reproductive health. Ornidazole (ORN) emerges as a novel environmental pollutant and compromises male fertility. However, the protective role and underlying mechanisms of docosahexaenoic acid (DHA) against ORN-induced testicular damage remain unexplored. Our clinical data showed that elevated serum ORN levels were negatively correlated with sperm quality. <i>In vivo</i>, ORN exposure led to impaired spermatogenesis, including meiotic disorders. Specifically, ORN impaired redox balance and reduced the expression of mitochondrial respiratory chain proteins (Ndufs1 and SdhB) in spermatocytes. Supplementation with docosahexaenoic acid significantly restored the quantity of DDX4-positive germ cells and SYCP3-positive spermatocytes and facilitated the progression from zygotene to pachytene stage. Mechanistically, DHA restored mitochondrial function and ROS levels by stimulating peroxisome proliferator-activated receptor gamma (PPARγ) signaling. Moreover, DHA reduced the expression of mitochondria-associated endoplasmic reticulum membranes (MAMs)-tethered voltage-dependent anion channel 1 (VDAC1), restoring MAMs balance and mitochondrial calcium homeostasis in a PPARγ-dependent manner. The DHA/PPARγ/VDAC1 axis in spermatocytes functions as a critical metabolic switch for regulating MAMs and ensuring mitochondrial homeostasis during meiosis. DHA is a promising therapeutic metabolite for oligoasthenozoospermia induced by environmental pollution.</p>

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Docosahexaenoic acid alleviates Ornidazole toxicity related to spermatogenic dysfunction by modulating PPARγ-dependent ER-mitochondrial uncoupling

  • 期刊论文

  • 发表日期：

    2026年5月27日

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  • Chuwei Li,
  • Shanmeizi Zhao,
  • Chongli Shi,
  • Shanshan Sun,
  • Zhaowanyue He,
  • Yao Xu,
  • Lu Zheng,
  • Ting Tang,
  • Shengjie Qiu,
  • Kuan Liang,
  • Hong Zhang,
  • Zhichuan Zou,
  • Yuming Feng,
  • Min Zang,
  • Jie Dong,
  • Jinzhao Ma,
  • Rujun Ma,
  • Chuanhai Fu,
  • Xie Ge,
  • Yong Wang,
  • Jun Jing,
  • Bing Yao

摘要

Male infertility has been increasing globally, raising concerns for reproductive health. Ornidazole (ORN) emerges as a novel environmental pollutant and compromises male fertility. However, the protective role and underlying mechanisms of docosahexaenoic acid (DHA) against ORN-induced testicular damage remain unexplored. Our clinical data showed that elevated serum ORN levels were negatively correlated with sperm quality. In vivo, ORN exposure led to impaired spermatogenesis, including meiotic disorders. Specifically, ORN impaired redox balance and reduced the expression of mitochondrial respiratory chain proteins (Ndufs1 and SdhB) in spermatocytes. Supplementation with docosahexaenoic acid significantly restored the quantity of DDX4-positive germ cells and SYCP3-positive spermatocytes and facilitated the progression from zygotene to pachytene stage. Mechanistically, DHA restored mitochondrial function and ROS levels by stimulating peroxisome proliferator-activated receptor gamma (PPARγ) signaling. Moreover, DHA reduced the expression of mitochondria-associated endoplasmic reticulum membranes (MAMs)-tethered voltage-dependent anion channel 1 (VDAC1), restoring MAMs balance and mitochondrial calcium homeostasis in a PPARγ-dependent manner. The DHA/PPARγ/VDAC1 axis in spermatocytes functions as a critical metabolic switch for regulating MAMs and ensuring mitochondrial homeostasis during meiosis. DHA is a promising therapeutic metabolite for oligoasthenozoospermia induced by environmental pollution.