Genes Involved in Long-Term Memory Are Expressed in Testis of Cryptorchid Boys and Respond to GnRHa Treatment

Abstract

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.

Keywords: Cryptorchidism; GnRHa; Long-term memory; Mini-puberty; RASGRF1; RNA sequencing; Testosterone.

Fig. 1

RNA sequencing data for RASGRF1 expression signals for samples before and after GnRHa treatment and for samples taken from untreated patients at time points corresponding to the treated samples (surgery I = before, surgery II = after). The standard deviation is given, and the FDR is shown at the top.