Involvement of epidermal growth factor deficiency in pathogenesis of oligozoospermia in streptozotocin-induced diabetic mice.

Based on previous findings that epidermal growth factor (EGF), which plays an important role in maintenance of spermatogenesis, is deficient in diabetic mice, the significance of EGF deficiency in the pathogenesis of oligozoospermia in streptozotocin-induced diabetic mice was studied. EGF levels in the submandibular glands and plasma of diabetic mice were 0.61 +/- 0.07 micrograms/mg tissue and 0.25 +/- 0.02 ng/ml (mean +/- SE), respectively, whereas those of normal mice were 1.63 +/- 0.08 micrograms/mg tissue and 0.54 +/- 0.04 ng/ml, respectively. The epididymal sperm counts of diabetic mice, 4.7 +/- 0.14 x 10(5)/mg tissue, were significantly lower (P less than 0.01) than those of normal mice, 6.0 +/- 0.10 x 10(5)/mg tissue. Administration of EGF (5 micrograms/mouse/day) to diabetic mice significantly (P less than 0.01) increased their sperm counts to 5.5 +/- 0.16 x 10(5)/mg tissue without affecting plasma levels of testosterone and glucose. Furthermore, insulin treatment (1 U/mouse/day) of diabetic mice restored the submandibular gland, plasma EGF concentrations, and sperm counts to normal levels. The restorative effects of insulin on sperm production appeared to be mediated, at least in part, by EGF, because its effect was significantly (P less than 0.01) reduced by the concomitant administration of EGF antiserum. In addition, the plasma testosterone levels of diabetic mice, 67 +/- 14.3 ng/ml, were lower that those of normal mice, 122 +/- 19.1 ng/ml. Administration of testosterone (1 mg/mouse/day) normalized the submandibular gland and plasma EGF levels and significantly increased sperm counts in the epididymis. These results suggest that EGF deficiency is a possible cause for the pathogenesis of oligozoospermia in diabetic mice.