Immunocytochemical localization of epidermal growth factor receptors in human testis from infertile subjects

Abstract

Objective: To investigate the immunolocalization of the epidermal growth factor receptor (EGFR) in normal and pathological human testis by immunocytochemical technique. Design: Cytologic specimens were obtained by bilateral fine needle aspiration (FNA) of the testis and stained in May Grunwald-Giemsa for the cytologic analysis; immunolocalization of EGFR was analyzed on duplicate slides from each testis using two anti-EGFR monoclonal antibodies and peroxidase-antiperoxidase technique. Setting: Infertility center of an academic unit. Patients: A total of 42 infertile patients, affected by various testicular diseases. The control group was made up of 10 normal sperm patients with autoimmune infertility and cytologic picture of normal spermatogenesis. Interventions: Exogenous FSH was administered 75 IU IM on alternate days for 3 months on 16 of the infertile patients who showed oligospermia and normal FSH plasma levels. Semen analysis and testicular FNA (and after cytologic and immunocytochemical studies) were repeated at 3 months of treatment. Main Outcome Measures: Luteinizing hormone and FSH plasma levels were determined by RIA methods; qualitative and quantitative parameters for the cytologic evaluation are reported in our previous works. Results: The cytologic analysis permitted identification of seven classes of infertile subjects, characterized by different cytologic pictures. Epidermal growth factor receptor immunostaining evidenced weak positivity on Sertoli and germ cells (with the exception of spermatozoa) in the presence of normal germ line and normal FSH plasma levels and strongly intense positivity in the presence of serious hypospermatogenesis, spermatogonial or spermatocytic arrest, and Sertoli cell-only syndrome. These conditions were characterized by higher FSH plasma levels than normal controls. All of the subjects who received exogenous FSH, with moderate hypospermatogenesis or spermatidic arrest, showed on Sertoli and germ cells a weak EGFR immunostaining before the treatment and intense immunostaining after the treatment. Conclusions: These results confirm recent demonstrations of EGFRs in human testis and evidence different EGFR immunostaining in the presence of various degrees of testicular damage, suggesting a role of this growth factor in growth and differentiation of the germ cells throughout spermatogenesis. The observation that intense EGFR immunostaining was found in subjects showing high FSH plasma levels and in all of the patients who received exogenous FSH, supports a possible role of this gonadotropin in the modulation of the EGFR expression.