Hong Jiyoung, Kim Sung Tae, Tranguch Susanne, Smith David F, Dey Sudhansu K
Pediatrics, Cell and Developmental Biology, Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Reproduction. 2007 Feb;133(2):395-403. doi: 10.1530/REP-06-0180.
FKBP52 is a member of the FK506-binding family of immunophilins and serves as a co-chaperone for steroid hormone nuclear receptors to govern appropriate hormone action in target tissues. Male mice missing Fkbp52 are infertile, and this infertility has been ascribed to compromised sensitivity of the anterior prostate, external genitalia, and other accessory sex organs to androgen. Here, we show additional defects contributing to infertility. We found that epididymal Fkbp52(-/-) sperm are sparse often with aberrant morphology, and they have reduced fertilizing capacity. This phenotype, initially observed in null males on a C57BL/6/129 background, is also maintained on a CD1 background. Expression studies show that while FKBP52 and androgen receptor are co-expressed in similar cell types in the epididymis, FKBP52 is also present in epididymal sperm flagella. Collectively, our results suggest that reduced number and abnormal morphology contribute to compromised fertilizing capacity of Fkbp52(-/-) sperm. This study is clinically relevant because unraveling the role of immunophilin signaling in male fertility will help identify new targets for male contraceptives and/or alleviate male infertility.
FKBP52是亲免素FK506结合家族的成员，作为类固醇激素核受体的辅助伴侣，在靶组织中调控适当的激素作用。缺失Fkbp52的雄性小鼠不育，这种不育归因于前列腺前部、外生殖器和其他附属生殖器官对雄激素的敏感性受损。在此，我们展示了导致不育的其他缺陷。我们发现附睾Fkbp52(-/-)精子数量稀少，形态常异常，且受精能力降低。这种表型最初在C57BL/6/129背景的基因敲除雄性小鼠中观察到，在CD1背景中也存在。表达研究表明，虽然FKBP52和雄激素受体在附睾的相似细胞类型中共表达，但FKBP52也存在于附睾精子鞭毛中。总体而言，我们的结果表明，数量减少和形态异常导致Fkbp52(-/-)精子受精能力受损。这项研究具有临床相关性，因为阐明亲免素信号在男性生育中的作用将有助于确定男性避孕药的新靶点和/或缓解男性不育。
