Effects of ethane dimethanesulphonate (eds) on testicular and epididymal structure, and plasma testosterone profiles in the goat (capra hircus)

Abstract

Effects of ethane dimethanesulphonate (EDS), a diester of suIphonic acid, on testicular and epididymal morphology and plasma testosterone profiles were studied using both light and electron microscopic techniques and radioimmunoassay (RIA). In order to determine stage specific changes in the seminiferous tubules, the seminiferous cycle, hitherto undescribed in goats, was described using light microscopy. Based on various cell associations and the accompanying changes in spermatid shape and location, eight (8) stages of the cycle with six (6) main divisions were identified. These stages appeared in the cycle with the following frequency; 34% (stage 1), 13% (stage 2), 12% (stage 3), 9% (stage4), 27% (stage5-7) and 5% (stage 8). When EDS was administered at a higher dose (75mg/kg) death of three members of the group (G 1) followed 24hrs later due to toxicity but the lower dose (2Smg/kg) was satisfactorily tolerated. In both cases, there was no noticeable effect of the compound on the Leydig cell structure six (6) days post-treatment. However, there was marked disruption of spermatogenesis characterized by spermatogonial degeneration, chromatin condensation in leptotene spermatocytes, failure of chromatin re-organization in stage 4 tubules, perip?eral re-distribution of chromatin in developing spermatids of stages 1, 2 and 5 and retention of maturation phase spermatids of stage 2 tubules. Sertoli cells showed accumulation of intracytoplasmic vesicles and intercellular vacuoles occurred within the epithelium. In the epididymis, there was region-specific involution of the epithelium. In the caput region, there was increased cytoplasmic density accompanied by enlarged vacuoles and paucity of secretory vesicles in the apical cytoplasm. The Golgi cisternae were IX dilated and disorganized and, in the basal aspect, large dense staining bodieslinclusions, degenerative mitochondria and lamellated bodies were observed. In the corpus, large vacuoles containing flocculent materials occurred in the entire cell cytoplasm but were particularly numerous and large in mid cytoplasm. There was a dramatic reduction in epithelial height in the cauda epididymis accompanied by sparse distribution of markedly shortened microvilli. The epithelial cells had extensively lobulated nuclei and disorganized cytoplasm with dilated Golgi apparatus and large conglomerations of tubular structures. Diurnal (circadian) and two-hour testosterone measurements at both dose levels (75mg/kg and 25mg/kg), irrespective of the duration of treatment, revealed no significant effect of the compound on testosterone production (P>0.05). The pre-treatment diurnal concentration was 0.82 ± 0.22 - 4.45 ± 1.79 nmoIlL and 0.45 ± 0.10 - 1.84 ± 1.11 nmol/L (n=8) for the morning and evening respectively. The morning values were significantly higher than the evening ones (P<0.05). One week post-treatment with the higher dose, the concentration was 0.31 ± 0.31- 4.02 ± 3.18 nmol/L and 0.30 ± 0.10 - 1.7 ± 0.50 nmol/L (n=2) while that of the lower dose was 1.03 ± 0.09 - 6.52 ± 3.08 nmol/L and 0.59 ± 0.06 - 2.13 ± 1.34 nmol/L (n=3) for both morning and evening respectively. Three weeks post-treatment, testosterone concentrations were 0.22 ± 0.22 - 0.59 ± 0 19 nmol/L and 0.27 ± 0.11 - 0.86 ± 0.5 nmol/L (n=2) (higher dose) and 1.16 ± 0.64 -4.43 ± 2.0 nmol/L and 0.52 ± 0.05 -1.7l. ± 0.96 nmol/L (n=3) (lower dose) for both morning and evening. The pre-treatment two-hour measurements were 0.81 ± 0.35 nmol/L -2.0 ± 1.27 nmol/L (n=l 0). Two weeks post-treatment, the levels were 1.13 ± 0.63 - 3.61 ± 3.19 x (n=2) and 0.86 ± 0.38 nmolfL - 3.00 ± 2.72 nmol/L (n=3) for both the higher and lower doses respectively. Taken together, these results suggest that in goats, EDS has no effect on Leydig cell function hence, no significant influence on testosterone levels but it has a direct effect on the seminiferous as well as epididymal epithelium.