Hadziselimovic Faruk, Gegenschatz-Schmid Katharina, Verkauskas Gilvydas, Demougin Philippe, Bilius Vytautas, Dasevicius Darius, Stadler Michael B
Cryptorchidism Research Institute, Kindermedizinisches Zentrum Liestal, Liestal, Switzerland.
Cytogenet Genome Res. 2017;152(1):9-15. doi: 10.1159/000477522. Epub 2017 Jul 13.
It has been known for many years that boys with unilateral or bilateral undescended testis (cryptorchidism) tend to have a low IQ, and those who belong to the high infertility risk (HIR) group perform less well at school than low infertility risk (LIR) patients. However, the molecular biological processes underlying this phenomenon are not understood. In this study, we report the outcome of testicular RNA profiling for genes involved in long-term memory formation. We analyzed the histology and the transcriptome of testicular biopsies from bilateral HIR cryptorchid boys, comparing those who received GnRHa treatment for 6 months after the first surgery with those who did not receive GnRHa before the second surgery. We found that GnRHa treatment alters the testicular mRNA levels of neuronal genes that are involved in long-term memory and testosterone synthesis. These data highlight a possible molecular link between cryptorchidism, impaired mini-puberty, and diminished cognitive functions. Our results are consistent with the hypothesis that hypogonadotropic hypogonadism in cryptorchid boys with altered mini-puberty may affect neuronal genes important for memory and learning, which could help explaining the negative correlation between cryptorchidism and intellectual abilities.
多年来人们已经知道，患有单侧或双侧隐睾症（睾丸未降）的男孩往往智商较低，而且那些属于高不孕风险（HIR）组的男孩在学校的表现不如低不孕风险（LIR）患者。然而，这种现象背后的分子生物学过程尚不清楚。在本研究中，我们报告了对参与长期记忆形成的基因进行睾丸RNA分析的结果。我们分析了双侧HIR隐睾男孩睾丸活检组织的组织学和转录组，将首次手术后接受6个月促性腺激素释放激素类似物（GnRHa）治疗的男孩与第二次手术前未接受GnRHa治疗的男孩进行了比较。我们发现，GnRHa治疗会改变参与长期记忆和睾酮合成的神经元基因的睾丸mRNA水平。这些数据突出了隐睾症、青春期发育不全和认知功能减退之间可能存在的分子联系。我们的结果与以下假设一致：青春期发育不全的隐睾男孩中的低促性腺激素性性腺功能减退可能会影响对记忆和学习很重要的神经元基因，这有助于解释隐睾症与智力能力之间的负相关关系。
