Quantitative restoration of advanced spermatogenic cells in adult male rats made azoospermic by active immunization against luteinizing hormone or gonadotropin-releasing hormone.

Abstract

The ability of testosterone to quantitatively restore spermatogenesis in rats made azoospermic by active immunization against LH or GnRH was examined. Sexually mature adult male rats (n = 15/group) were actively immunized against ovine LH or GnRH-human serum globulin conjugate, while control rats (n = 10) were injected with saline. After 10 weeks of immunization, five rats per group were euthanized. For each rat, trunk blood was collected for determination of LH, FSH, and testosterone by RIA; seminiferous tubule fluid (STF) was collected from one testis per rat, and testosterone concentration was measured by RIA; the number of advanced spermatids per testis was determined from the contralateral testis. The results obtained after 10 weeks of treatment were as follows. 1) Serum LH and FSH were undetectable by RIA in GnRH-immunized rats. 2) Serum testosterone was undetectable in both the LH- and GnRH-immunized groups. 3) The testosterone concentration in STF (STF-T) was reduced from the control value of about 64 ng/ml to about 2 ng/ml in the LH- and GnRH-immunized rats. 4) LH- and GnRH-immunized rats were azoospermic. After the initial 10-week treatment period, five rats in each of the LH- and GnRH-immunized groups received 24-cm testosterone-filled polydimethylsiloxane (PDS-T) capsules (3 x 8 cm long) sc. The remaining immunized rats (n = 5/group) received empty capsules. Two months later, all rats were euthanized. Testis weights, serum testosterone, and STF-T concentrations remained significantly reduced in LH- and GnRH-immunized rats that did not receive testosterone supplementation, and the rats remained azoospermic. STF-T concentrations rose significantly (P less than 0.05) in the LH- and GnRH-immunized rats that received PDS-T, but were still significantly less (by approximately 80%) than the concentration in intact controls. Nonetheless, implantation of PDS-T caused restoration of advanced spermatogenic cells in the testes of both LH- and GnRH-immunized rats to numbers that were not significantly different from the number in controls. These data indicate that 1) testosterone is capable of quantitatively restoring spermatogenesis in rats actively immunized against LH or GnRH, suggesting that FSH may not be required for the restoration of spermatogenesis in adult rats; and 2) quantitatively complete restoration of spermatogenesis can occur at STF-T concentrations that are significantly reduced compared to those in intact controls.