Local expression of epidermal growth factor-like growth factors in human testis and its role in spermatogenesis

Microdissection testicular sperm extraction (micro-TESE) has revealed that spermatogenesis in nonobstructive azoospermia (NOA) patients is heterogeneous, even in the same testis, but there is no information regarding growth factors to support spermatogenesis. We investigated the involvement of epidermal growth factor (EGF)-like growth factors, which play important roles in cell proliferation and differentiation in NOA patients who underwent micro-TESE. Testicular samples were obtained from 5 fertile men (15 samples), 5 prostate cancer patients receiving maximum androgen blockade (10 samples), and 13 NOA patients who underwent micro-TESE (50 samples). The expression of the mRNA for EGF, heparin binding (HB)-EGF, amphiregulin, epiregulin, betacellulin, and transforming growth factor (TGF)-α were analyzed by real-time polymerase chain reaction analysis and adjusted using the expression of glyceraldehyde-3-phosphate dehydrogenase. Heterogeneous expression of these EGF-like growth factors were observed even in the same testis. The expression of HB-EGF, amphiregulin and TGF-α in NOA and prostate cancer patients was significantly lower than observed in fertile controls. In NOA patients, expression in the testicular sample comprising mature sperm was significantly higher than those without mature sperm, indicating that HB-EGF, amphiregulin, and TGF-α are considered to participate in creating a suitable niche for spermatogenesis. Considering the findings that ablation of gonadotropin inhibited and human chorionic gonadotropin stimulation increased these EGF-like growth factors, the expressions are presumably under gonadotropin regulation.