Sertoli cell inactivation by cytotoxic damage to the human testis after cancer chemotherapy

Objective To assess Sertoli cell involvement in postchemotherapy azoospermia. Design Case report. Setting Teaching hospital. Patient(s) A 31-year-old azoospermic man who underwent cancer cytotoxic chemotherapy for non-Hodgkin's lymphoma at 13 years of age. Intervention(s) Testicular biopsy specimens were obtained for sperm recovery in preparation for intracytoplasmic sperm injection. The biopsy specimens were evaluated by quantitative immunohistochemistry for the immature Sertoli cell markers cytokeratin 18 (CK-18) and D2-40. Main outcome measure(s) Extent of immature Sertoli cells. Result(s) A fraction of Sertoli cells (13%) in the atrophic tubules of this patient reexpressed the intermediate filament protein CK-18, which is normally absent after puberty, but not the D2-40 antigen, an Mr 40,000 a-linked membrane glycoprotein, whose loss of expression at puberty marks an irreversible step in Sertoli cell maturation. Tubules with normal spermatogenic progression lined by Sertoli cells negative for CK-18 were also observed. Conclusion(s): A fraction of Sertoli cells of this patient initially progressed to full maturation at puberty and reverted to a dedifferentiated state marked by reexpression of CK-18 as a consequence of chemotherapy. This inactivation of Sertoli cells caused by the cytotoxicity of the chemotherapeutic drugs may have contributed to the spermatogenic impairment and resulting infertility.