孕期非那雄胺暴露致子代雄性小鼠生殖器官发育异常  

Abnormal development of genital organs in offspring male mice exposed to finasteride during pregnancy

作　　者：范霞[1] 李飞[1] 黄璜[1] FAN Xia;LI Fei;HUANG Huang(Department of Pediatric Surgery,Guizhou Provincial People′s Hospital,Guiyang 550001,China)

机构地区：[1]贵州省人民医院儿外科

出　　处：《中国病理生理杂志》2020年第2期323-328,共6页Chinese Journal of Pathophysiology

基　　金：贵州省科技计划项目(黔科合LH字【2016】7177号)

摘　　要：目的:探讨孕期非那雄胺暴露对子代雄性小鼠生殖器官发育的影响。方法:CD-1小鼠在受孕后0~17 d给予非那雄胺处理,通过宏观观察、解剖分析与组织形态学染色观察子代雄性小鼠生殖器官的发育情况;通过免疫荧光染色分析子代雄性小鼠精子发生情况。结果:宏观观察结果显示,孕期非那雄胺暴露可导致子代雄性小鼠外生殖器官畸形,表现为阴囊未完全融合及阴茎畸形;此外,还观察到小鼠肛门与生殖器的距离显著缩短(P<0.01)。解剖分析结果显示,孕期非那雄胺暴露可导致子代雄性小鼠睾丸不同程度的不完全下降及长度显著缩短(P<0.01)。组织形态学结果显示,各阶段阴茎长度均显著缩短(P<0.01);睾丸生精小管密度和生精小管管腔成熟精子数均显著降低(P<0.01),生精小管管腔和睾丸间质间隙均显著增大(P<0.01)。免疫荧光染色结果显示,睾丸中支持细胞、睾丸间质细胞和精原细胞的密度均显著降低(P<0.01);生精小管细胞的caspase-3荧光强度显著增加(P<0.01),Ki67与沙漠刺猬因子(desert hedgehog,Dhh)荧光强度均显著降低(P<0.01)。结论:孕期非那雄胺暴露可导致子代小鼠生殖器官发育异常并影响精子发生。AIM:To investigate the effects of finasteride exposure during pregnancy on the development of reproductive organs in offspring male mice.METHODS:CD-1 mice were treated with finasteride from 0 to 17 d after conception.The development of reproductive organs in the offspring male mice were observed by macroscopy,anatomical analysis and histological staining.The spermatogenesis was analyzed by immunofluorescence staining.RESULTS:Macroscopic observation showed that fenasteride exposure during pregnancy resulted in external genital malformations in the offspring male mice,which were manifested as incomplete scrotal fusion and penile malformation.In addition,the anogenital distance was significantly shortened(P<0.01).Histological staining showed that the length of penis at each stage was significantly shortened(P<0.01),the density of seminiferous tubules in testis and mature spermatozoa in seminiferous tubules were significantly decreased(P<0.01),and the luminal space size of seminiferous tubules and interstitial space size of testises were significantly increased(P<0.01).Immunofluorescence staining showed that the densities of Sertoli cells,Leydig cells and spermatogonium in testis were significantly reduced(P<0.01),and the fluorescence intensity of caspase-3 in spermatogenic tubule cells was increased significantly(P<0.01).However,the fluorescence intensity of Ki67 and desert hedgehog(Dhh)was decreased significantly(P<0.01).CONCLUSION:Finasteride exposure during pregnancy results in abnormal development of reproductive organs in offspring male mice and affects spermatogenesis.

关 键 词：非那雄胺 孕期暴露 性发育障碍 生殖器官 精子发生 

分 类 号：R363.2[医药卫生—病理学] R697[医药卫生—基础医学]