Testicular mosaicism in non-mosaic postpubertal Klinefelter patients with focal spermatogenesis and in non-mosaic prepubertal Klinefelter boys

ABSTRACT The aim of the study is to investigate testicular mosaicism in non-mosaic postpubertal Klinefelter Syndrome patients and in non-mosaic prepubertal Klinefelter boys Testes of the males with non-mosaic Klinefelter Syndrome at different developmental stages were used. Immunohistochemical and fluorescent in situ hybridization analyses were applied for X chromosome ploidy in testis-specific cells in testicular biopsy samples from non-mosaic Klinefelter Syndrome patients. According to our findings, all analyzed spermatogonia in both postpubertal and prepubertal non-mosaic Klinefelter Syndrome patients have a 46,XY karyotype. However, while the Sertoli cells surrounding spermatogonia in postpubertal samples also have a 46,XY karyotype, the Sertoli cells surrounding spermatogonia in prepubertal samples have a 47,XXY karyotype. Peritubular myoid cells and Leydig cells may also have mosaicism in both postpubertal patients and prepubertal boys. In conclusion, we confirmed in situ using cell-specific markers that testicular mosaicism exists in non-mosaic Klinefelter Syndrome patients. Therefore, we hypothesize that focal spermatogenesis seen in some postpubertal Klinefelter Syndrome patients originates from euploid spermatogonia and Sertoli cells. Additionally, our findings suggest that only spermatogonia that have lost their X chromosome can survive. Furthermore, our data suggest that spermatogonia lose the extra X chromosome during fetal or neonatal life, while Sertoli cells lose it around puberty. These findings will lay the groundwork for new studies on exactly when and by which mechanism an extra X chromosome is lost in spermatogonia and Sertoli cells.