度他雄胺对大鼠附睾精子成熟和生育的影响

目的通过度他雄胺对大鼠附睾精子和生育的影响,探索调节雄性生育的睾丸后作用靶点。方法使用度他雄胺20和40 mg/(kg.d)大鼠灌胃给药,连续2周。给药结束后雄雌鼠按1∶2合笼,计算生殖指数;采用计算机辅助精子分析系统分析精子活力和形态;采用SYBR-14和PI双重荧光染色计算精子存活率;采用Elisa法测定大鼠睾酮(T)和双氢睾酮(DHT)血清浓度;采用HE染色法对各组睾丸、附睾进行组织学分析。结果度他雄胺低、高剂量组双氢睾酮浓度均显著下降,分别为0.54和0.28 nmol/L(P<0.01),精子活力明显降低,分别为39.0%和28.7%(P<0.01),畸形率分别增加为10.3%和15.6%(P<0.05),最后受孕率分别降为62.5%和38.4%。而睾酮水平和交配指数均无明显变化(P>0.05),睾丸和附睾亦无明显病理学改变。结论度他雄胺通过抑制DHT生成,影响附睾精子成熟而导致大鼠不育,为今后男性避孕和不育药物研发提供了新思路。

Alteration of Rat Sperm Maturation and Fertility Induced by Dutasteride Treatment

Objective To study post-testis targets related to male contraception and infertility caused by dutasteride treatment on rat sperm maturation and fertility.Methods Rats were treated with 20 and 40 mg/kg/d dutasteride for consecutive 14 days.Each male rat was paired with 2 female rats and the reproductive indices were assessed.Sperm motility and morphology were analyzed by a computer-assisted sperm analysis system.The sperm survival rate was assessed by SYBR-14 and PI fluorescent staining.Serum dehydrotestosterone(DHT) and T of rats were detected by ELISA.Histological examination of testis and epdidymis was conducted by HE staining.Results The DHT level,sperm motility and the pregnancy index by treatment were all significantly decreased(P<0.05 or 0.01),while the abnormal sperm rate was increased(P<0.05).But there was no difference in serum T level between dutasteride treated and control males(P>0.05).The histology of testis and epididymis was also unaffected by treatment.Conclusions Dutasteride can induce infertility in male rats through inhibiting serum DHT level and interfering with epididymal sperm maturation,which may open a new approach for research on male contraception and fertility.