促红细胞生成素促进胚胎期氟他胺诱导隐睾生殖发育的实验研究

Erythropoietin promotes reproductive development rat offsprings of flutamideinduced cryptorchidism in embryonic stage

目的 探讨促红细胞生成素（erythropoietin,EPO）是否具有促进胚胎期氟他胺（flutamide,Flu）诱导隐睾生殖细胞发育的生物效应。 方法 氟他胺诱导后的SD仔鼠出生后按随机数字表法分为3组：Flu组（n=36）、Flu＋EPO组（n=42）和Flu＋PBS组（n=32），正常饲养的SD仔鼠分为正常对照组（n=40）及EPO组（n=16）；Flu组和正常对照组常规饲养，Flu＋EPO组、EPO组及Flu＋PBS组于出生后（postnatal day,PD）1-7 d隔天腹腔注射 1 000 U/kg外源性EPO或同等体积的PBS。出生后25 d统计隐睾发生率及睾丸脏器系数，观察睾丸组织学变化，统计生殖指数，测量曲细精管横截面积和直径，免疫组织化学法检测睾丸间隙连接蛋白Connexin43在睾丸组织中的表达。 结果 Flu＋EPO组隐睾发生率为38.1%（16/42），较Flu组[55.6%（20/36）]及Flu＋PBS组[53.1%（17/32）]降低，Flu＋EPO隐睾组生精上皮细胞数量、睾丸脏器系数、生殖指数、平均曲细精管面积及直径均明显大于Flu组（P〈0.01，P〈0.05），且与正常对照组差异无统计学意义。EPO能够促进Connexin43蛋白在隐睾组织中的正常表达。 结论 外源性EPO可以降低胚胎期Flu暴露后隐睾发生率，促进隐睾生殖细胞发育。

Objective To investigate the biological effect of erythropoietin （EPO） on promoting the germ cell development in cryptorchidism induced by flutamide （Flu） in embryonic stage. Methods Flu-induced rat offsprings were randomly divided into 3 groups： Flu group （n=36）, Flu＋EPO group （n=42）, and Flu＋PBS group （n=32）. Normal newborn rats were divided into control group （n=40） and EPO group （n=16）. The Flu group and control group received conventional breeding, while the Flu＋EPO group, EPO group, and Flu＋PBS group were treated with 1 000 U/（kg·d） recombinant rat erythropoietin （RrEPO） by intraperitoneal injection on postnatal day （PD） 1,PD 3, PD 5 and PD 7 or an equal volume of PBS. The incidence of cryptorchidism, organ index of testis, and reproduction index were evaluated. The testicular histology, and the area and diameter of seminiferous tubules were observed. And the expression of testis Connexin43 was detected by immunohistochemistry. Results The incidence of cryptorchidism in the Flu＋EPO group was 38.1% （16/42）, which was lower than 55.6% （20/36） in the Flu group and 53.1% （17/32） in the Flu＋PBS group. The germ cell number, organ index, reproduction index, and area and diameter of seminiferous tubules were greater in the Flu＋EPO group than the Flu group （P〈0.01, P〈0.05）, but there was no significant difference compared with the control group （P〉0.05）. RrEPO promoted normal expression of Connexin43 protein in the testis of the Flu-induced cryptorchidism. Conclusion The incidence of Flu-induced cryptorchidism can be decreased by RrEPO treatment after birth. EPO may contribute to promoting the germ cell development after cryptorchidism.