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大鼠孕/哺乳期暴露于雷公藤甲素对雄性子鼠生殖系统的影响
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| 篇名： | 大鼠孕/哺乳期暴露于雷公藤甲素对雄性子鼠生殖系统的影响 |
| TITLE： | Effects of triptolide exposure during pregnancy/lactation on the reproductive system of male offspring in rats |
| 摘要： | 目的 探讨雌性大鼠孕期及哺乳期暴露于雷公藤甲素（TP）对雄性子鼠生殖系统发育及功能的影响，为孕期和哺乳期的安全用药提供参考。方法将孕鼠随机分为对照组（12只，生理盐水）和T1～T4组[分别有12、13、14、17只，给药剂量分别为200、400、600、800μg/（kg·d）]。每日灌胃相应药物/生理盐水1次，直至子鼠出生并断乳，灌胃体积均为2mL/只。哺乳喂养60d后，称定雄性子鼠生殖系统脏器质量，计算脏器系数，观察其睾丸和附睾以及精子形态，测定其附睾组织中精子活力、精子数量以及血清中促性腺激素释放激素（GnRH）、卵泡刺激素（FSH）、黄体生成素（LH）、睾酮（T）水平和精子中糖原合酶激酶3α（GSK3α）、磷酸化GSK3α（p-GSK3α）、蛋白磷酸酶1γ2（PP1γ2）蛋白的表达情况。结果与对照组比较，T1～T4组子鼠的睾丸质量、附睾质量和血清中GnRH、T水平以及精子中PP1γ2蛋白的相对表达量，T2～T4组子鼠的精囊腺质量、精囊腺系数、精子总数、精子浓度、精子活动力以及精子中GSKα、p-GSK3α蛋白的相对表达量，T3、T4组子鼠的附睾系数，T4组子鼠的睾丸系数、精子平均路径速度、精子曲线速度均显著降低或减小（P＜0.05）；T1～T4组子鼠的畸形精子数、精子畸形率和血清中FSH、LH水平均显著增多或升高（P＜0.05）；T1～T4组子鼠的睾丸生精小管上皮细胞数量均减少，附睾组织内可见上皮细胞变性坏死、间质内伴少量炎症细胞浸润等现象。结论雌性大鼠孕期及哺乳期暴露于TP可导致雄性子鼠生殖器官发育异常、精子生成减少、精子活性降低、雄激素合成减少，从而对子鼠生殖系统发育产生负面影响；其机制可能与下调GSK3α、p-GSK3α和PP1γ2蛋白表达有关。 |
| ABSTRACT： | OBJECTIVE To investigate the effects of triptolide （TP） exposure during pregnancy and lactation on the reproductive system development and function in male offspring of rats， providing a reference for medication safety during pregnancy and lactation. METHODS Pregnant rats were randomly divided into control group （12 rats， normal saline） and T1-T4 groups [12， 13， 14， 17 rats that received TP at 200， 400， 600， and 800 μg/（kg·d） respectively]. They were given relevant medicine/normal saline intragastrically， once a day， until the offspring were born and naturally weaned， the intragastric administration volume of each rat was consistently 2 mL. After 60 days of feeding， reproductive organ weights and coefficients were measured in male offspring， testicular and epididymal histology and sperm morphology were observed. Sperm motility， sperm count， and serum levels of gonadotropin-releasing hormone （GnRH）， follicle stimulating hormone （FSH）， luteinizing hormone （LH）， and testosterone （T） in the epididymides were analyzed. Protein expressions of glycogen synthase kinase 3α （GSK3α）， phosphorylated GSK3α （p-GSK3α）， and phosphatase 1γ2 （PP1γ2） in sperm were also determined. RESULTS Compared with the control group， the testicular and epididymal weights， serum levels of GnRH and T， the relative protein expression of PP1γ2 were significantly decreased in T1-T4 groups. Additionally， in the T2 to T4 groups， there were significant reductions in the weight and coefficient of the seminal vesicle， total number of sperm， sperm concentration， sperm motility as well as relative protein expressions of GSKα， p-GSK3α in the offspring rats. Furthermore， the epididymal coefficient in the T3 and T4 groups， the testicular coefficient， mean sperm track velocity and sperm curvature velocity in the T4 group were significantly decreased （P＜ 0.05）； the number of abnormal sperm， rate of sperm abnormality， and levels of FSH and LH in the offspring rats of the T1 to T4 groups were all significantly increased （P＜0.05）； in the offspring rats of the T1 to T4 groups， there was a decrease in the number of epithelial cells in the seminiferous tubules of the testes. Within the epididymal tissue， degenerative and necrotic changes in the epithelial cells were visible， accompanied by mild infiltration of inflammatory cells in the stroma. CONCLUSIONS TP exposure during pregnancy and lactation disrupts reproductive organ development， impairs spermatogenesis and sperm motility， as well as suppresses androgen synthesis in male offspring，thereby having a negative impact on the development of the reproductive system. These effects may be mechanistically linked to regulation of GSK3α， p-GSK3α and PP1γ2 protein expressions. |
| 期刊： | 2025年第36卷第05期 |
| 作者： | 张晓敏；荆嘉慧；康玉军 |
| AUTHORS： | ZHANG Xiaomin，JING Jiahui，KANG Yujun |
| 关键字： | 雷公藤甲素；孕期；哺乳期；雄性子鼠；生殖毒性 |
| KEYWORDS： | triptolide； pregnancy； lactation； male offspring rat； reproductive toxicity |
| 阅读数： | 2 次 |
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