Fragile X syndrome is associated with expansion of a repeated triple CGG sequence in the 5′ region of the FMR-1 gene, resulting in absence of production of FMRp protein due to blocking of the FMR1 transcription gene. The authors report a hormonal, histological, and immunohistochemical study of one case, focusing on the origin of macroorchidism and the variability of testicular functions in these patients. Our observations confirm the existence of interstitial tissue hyperplasia, thickening of the peritubular basal membrane and an increased external diameter of the seminiferous tubes with no morphological anomalies in the Leydig or Sertoli cells. Spermatogenesis in fragile X Syndrome patients has been extensively studied: it may be normal, incomplete or patients may present impaired spermatogenesis in the late stages. These later lesions, which are associated with interstitial oedema, resemble the lesions observed after vasectomy, suggesting the role of raised peritubular pressure and anti-sperm antibodies. In our study, no antibodies were detected in the serum and oedema was minimal, which tends to discredit this theory. The role of the FRMp protein in spermatogenesis remains controversial. Immunolabelling on slides prepared from testicular biopsies confirms that a complete form of mutation is not seen in the germ cells. Although the FMRp protein might be necessary for survival of germ cells, its persistent expression in the testis could explain preservation of spermatogenesis in some patients. Our results are consistent with the hypothesis that the varying degrees of impaired spermatogenesis could be related to the number of germ cells not affected by the complete mutation. However, additional data are necessary to fully understand the variability of spermatogenesis and the pathophysiology of macroorchidism observed in patients with fragile X syndrome.
