Introduction

Hypogonadism is a prominent feature of Prader-Willi syndrome (PWS); cryptorchism occurs in approximately 90% of male cases. Hypogonadism in PWS has long been believed to be hypothalamus-related, resulting in low gonadotropin levels. Recent studies have suggested that hypothalamic and primary testicular dysfunction contribute to hypogonadism in PWS (Human Reproduction, 2015). No men with PWS have been reported to have fathered children. This is attributed to dysfunctional spermatogenesis secondary to cryptorchism, hypogonadism, or decreased libido in adulthood; however, a clear cause has not been identified. Further, only a few testicular histopathology reports have been published regarding males with PWS. Here, we present a report comparing the testicular histopathologies and endocrinologies of boys with PWS and cryptorchism with boys having isolated cryptorchism ._x000D_

Methods

This study included 9 boys, 14–32-months-old (mean age, 21 months), with PWS who underwent orchidopexy at Nagoya City University Hospital between April 2002 and February 2016. The testes were position in the abdomen (2 cases), inguinal canal (7), high scrotal(7), or were retractile (2). Testicular biopsies were performed in 8 cases (15 testes). Sixteen cases (32 testes) of a corresponding age and testis position were included in a control group. The histological findings were evaluated to determine the seminiferous tubule fertility index. “Decreasing spermatogonia� was defined as <60% of the seminiferous tubules being positive for spermatogonia (J Urol, 2008). Serum levels of LH, FSH, testosterone (T), Inhibin B, and anti-mullerian hormone (AMH) were determined immediately before orchidopexy.

Results

Boys with PWS had significantly smaller testicular volumes than did the controls (mean values, 0.25 mL vs 0.62 mL; p < 0.05), and also had significantly fewer spermatogonia (87% vs 47%, p = 0.01). The endocrinological results were as follows: the laboratory data for the PWS boys (mean age, 23 months) showed LH at 0.1 IU/L (range, less than 0.2), FSH at 0.94 IU/L (0.5-1.8), T at <0.05 ng/mL(less than 0.1), AMH at 56 ng/mL, and Inhibin B at 38.2 pg/mL; those of the control group (mean age, 21 months) showed LH at 0.1 IU/L, FSH at 1.75 IU/L, T at <0.05 ng/mL, AMH at 234 ng/ml, and Inhibin B at 183 pg/mL.

Conclusions

Boys with PWS-associated cryptorchism show a reduced number of spermatogonia, beginning in infancy, suggesting that spermatogenic dysfunction is one cause of patient infertility. Low Inhibin B levels also suggest that boys with PWS have primary testicular dysfunction.

Funding

none