Leydig cell resistance to the cytotoxic effect of ethylene dimethanesulphonate in the adult rat testis

Abstract

Weekly doses of the Leydig cell cytotoxic ethylene dimethanesulphonate (EDS) were administered to adult male rats in an attempt to study the endocrine activity of the testis in the absence of Leydig cells. One week after the first dose serum testosterone and LH concentrations and seminal vesicle weights were close to levels in castrated rats and testicular human chorionic gonadotrophin (hCG) binding was severely depressed. These changes were maintained for a further week but subsequently began to return to, but did not achieve, control levels. After six weekly doses seminal vesicle weight and serum testosterone concentrations were significantly higher than in the castrated rats. Serum LH concentrations were declining towards control values at 4 weeks but had risen again at 6 weeks. Serum FSH concentrations were raised to about 50% of the value in castrated rats throughout the period studied. Testis weight and hCG binding, which initially fell, were partially restored at 6 weeks and spermatogenesis was recovering. The data show that responses of the testis to multiple doses of EDS are similar to those after a single dose. This apparent resistance indicates that the regenerating Leydig cells are functionally different from the mature Leydig cell. The similarities between the maturing Leydig cell seen after EDS destruction and those in the immature rat suggest that EDS will provide a valuable model for the investigation of Leydig cell physiology.

Stage‐Dependent changes in spermatogenesis and sertoli cells in relation to the onset of spermatogenic failure following withdrawal of testosterone

“…It has been suggested that EDS may be directly toxic to immature Sertoli cells in culture (Roberts and Griswold, 1990) and that EDS can disrupt spermatogenesis in adult rats when administered in combination with long-term estrogen treatment (Sprando et al, 1990). Other evidence supports the contention that EDS is not directly cytotoxic to the seminiferous epithelium: (1) androgen supplementation prior to or given intermittently after in vivo EDS treatment can maintain normal spermatogenesis with no disruptive effects on the Sertoli cells (Jackson and Jackson, 1984;Sharpe et al, 1988131, and (2) weekly injections of EDS given to adult rats for 6 weeks have no greater antispermatogenic effects compared to a single administration (Morris, 1985).…”

Rapid recovery of leydig cell population in rar cryptorchid testes after ethanedime-thanesulfonate injury: Immuno-histochemical studies.

“…Serum testosterone concentrations in EDS-injected rats were lower during the first two weeks following EDS treatment, and though they increased were lower than those of controls at 3-4 weeks after EDS injury. Nonetheless, testosterone levels did not differ significantly from control levels beyond 6 weeks after EDS injection (6). Ultrastructurally, only a few attenuated mesenchymal cells remained in the peritubular and/or perivascular regions within intertubular areas of testes 7 days after EDS injection.…”

Cell‐cell interactions in the control of spermatogenesis as studied using leydig cell destruction and testosterone replacement

“…4), containing no detectable testosterone (Fig. 5 ) , and with no other obvious testicular effects of the EDS (Morris, 1985;Verhoeven et al, 1989); however, after about 10-12 days the Leydig cells begin to regenerate and by 42 days are restored in normal num-The Spermatogenic Cycle Fig. I .…”