Sun Xiaoyan, Ying Jia, Ma Xuan, Zhong Yunong, Huo Ran, Meng Qingxia
Center of Reproduction and Genetics, State Key Laboratory of Reproductive Medicine and Offspring Health, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou 215000, China.
State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing 210000, China.
Toxics. 2025 Sep 9;13(9):763. doi: 10.3390/toxics13090763.
This study evaluated the reproductive toxicity and reversibility of gossypol exposure in female Institute of Cancer Research (ICR) mice using the Targeted Risk Assessment of Environmental Chemicals (TRAEC) framework. Mice treated with gossypol (20 mg/kg/day, 30 days) showed reduced body weight (35.90 ± 3.19 g vs. 30.26 ± 0.91 g, < 0.001), depletion of primordial follicles (46.2 ± 4.8 vs. 27.5 ± 3.6, < 0.01), and impaired oocyte maturation, with polar body extrusion decreasing from 65.9% to 22.6% at 60 μM ( < 0.0001). In the human granulosa-like tumor cell line (KGN), apoptosis increased to 91.1% at 20 μg/mL compared with 11.46% in controls ( < 0.0001). Proteomic profiling identified 151 differentially expressed proteins, enriched in steroidogenesis, immune regulation, and mitochondrial metabolism. After one-month withdrawal, partial morphological recovery was observed, but endocrine function remained impaired. The TRAEC risk score of 4.68 classified gossypol as a moderate reproductive toxicant. These findings indicate that gossypol damages ovarian reserve and oocyte competence, with only partial reversibility, highlighting the need for caution in its clinical use.
本研究使用环境化学品靶向风险评估（TRAEC）框架，评估了棉酚暴露对雌性癌症研究所（ICR）小鼠的生殖毒性及可逆性。用棉酚处理的小鼠（20毫克/千克/天，30天）体重减轻（35.90±3.19克对30.26±0.91克，<0.001），原始卵泡耗竭（46.2±4.8对27.5±3.6，<0.01），卵母细胞成熟受损，在60微摩尔时极体排出率从65.9%降至22.6%（<0.0001）。在人颗粒细胞瘤细胞系（KGN）中，20微克/毫升时细胞凋亡率增至91.1%，而对照组为11.46%（<0.0001）。蛋白质组分析鉴定出151种差异表达蛋白，富集于类固醇生成、免疫调节和线粒体代谢。停药一个月后，观察到部分形态恢复，但内分泌功能仍受损。棉酚的TRAEC风险评分为4.68，被归类为中度生殖毒物。这些发现表明，棉酚会损害卵巢储备和卵母细胞功能，且仅有部分可逆性，这凸显了其临床使用时需谨慎的必要性。
