中国药房2025，Vol.36Issue(5)：558-562,5.DOI:10.6039/j.issn.1001-0408.2025.05.09
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
Effects of triptolide exposure during pregnancy/lactation on the reproductive system of male offspring in rats
摘要
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.关键词
雷公藤甲素/孕期/哺乳期/雄性子鼠/生殖毒性Key words
triptolide/pregnancy/lactation/male offspring rat/reproductive toxicity分类
医药卫生引用本文复制引用
张晓敏,荆嘉慧,康玉军..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[J].中国药房,2025,36(5):558-562,5.基金项目
甘肃省自然科学基金(青年科技基金)项目(No.22JR-5RA1015) （青年科技基金）
兰州大学学生创新创业行动计划立项(No.20240050002) （No.20240050002）
