EFFECT OF CADMIUM, SELENIUM AND CO-ADMINISTRATION ON TESTIS, DUCT SYSTEM AND EPIDIDYMAL SPERM DNA INTEGRITY AND HORMONAL PROFILE IN SPRAGUE DAWLEY RAT.

Abstract

Purpose of this study was to evaluate the consequences of short term (28 days) exposure to low (0.5mg/kgb.wt.) and high (1mg/kg b.wt.) doses of Cadmium and Selenium alone and in combination on alternate days on the reproductive system of adult male Sprague Dawely rats. In the present study, low and high doses of Cadmium or Selenium on alternate days (for 28 days) did not effected weekly body weight of rats significantly while Cd+Se treatment caused significantly reduction in weekly body weight compared to control. Cadmium and Selenium treatments on alternate days, alone and in combination showed no significant effect on testicular weight at both dose levels. Present study found that testicular width and length was not affected by low dose of all treatments, but mean testicular width and length was significantly decreased in high dosed Cadmium and Cd+Se groups. In the present study, epididymis weight was not effected by Cadmium, Selenium and Cd+Se in both low and high dosed groups compared to control whereas epididymal length was not effected by any treatment in low dose group, but at high dose level individual treatment with Cadmium and Selenium caused significant reduction in epididymal length compared to control. In this investigation, at low dose level vas deferens weight and length was not affected by all the three treatments while vas deferens width was decreased by Cadmium treatment and other two treatments showed no effect on width of vas deferens at this dose level. In high dosed group, significant reduction was found in vas deferens weight and length by Cadmium, Selenium and Cd+Se treatments compared to control, while vas deferens width was decreased by Cadmium and Cd+Se treatment compared to control. Histological study of testicular sections showed that Cadmium alone and in combination caused irregular thickening of tunica and widening of interstitium in the present study, Leydig cell nuclear diameter was not effected by Cadmium treatment at low level, but significantly increased by Selenium and Cd+Se treatment compared to control. In high dosed group, micrometric analysis showed significant decrease in leydig cell nuclear diameter in Cadmium and Cd+Se treated group compared to control, while Selenium treatment caused no effect on this dose level on nuclear diameter of leydig cells. Sertoli cell nuclear diameter was significantly decreased by Cadmium treatment at low dose level compared to control, while Selenium and Cd+Se treatment showed no effect on Sertoli cell nuclear diameter at this dose level. In high dosed groups, reduction in Sertoli cell nuclear diameter was significantly caused by Cadmium and Cd+Se treatment compared to control. In the present investigation, nuclear diameter of spermatogonia was not effected by low dosed Cadmium, Selenium and Cd+Se groups, while at high dose, all the treatments caused highly significant decrease in nuclear diameter of spermatogonia. Nuclear diameter of primary spermatocyte was significantly decreased by Cadmium and Cd+Se treatment at both low and high dose level while, Selenium treatment did not influenced nuclear diameter of primary spermatocyte at low and high dosage. Secondary spermatocyte nuclear diameter was significantly reduced in both low and high dose groups with Cadmium, Selenium and Cd+Se treated groups. In present study, Cadmium, Selenium and Cd+Se treatment caused highly significant reduction in nuclear diameter of round spermatid at low dose level, but at high dose level no effect on nuclear diameter of round spermatids was found by Cadmium and Selenium individual treatments, while in Cd+Se treatment significant decrease in nuclear diameter of round spermatid was xviii Abstract obvious. Daily sperm production and its efficiency was significantly reduced by the low and high dosed Cadmium and Selenium treated group compared to control. Co- administration of both chemicals at low dose level resulted in highly significant decrease in daily sperm production and its efficiency in rat, but at high dose level surprisingly co-exposure showed no significant effect on daily sperm production and its efficiency compared to control. This study demonstrates that Cadmium treatment at low and high dose resulted in significant decrease in mean serum cholesterol level. Individual treatment of Selenium caused significant elevation in serum cholesterol level in low dosed group while in high dosed treatment, no significant difference was observed compared to control. Cd+Se at both doses caused no significant effect on serum cholesterol level compared to control. Serum testosterone was significantly decreased by alone treatment of Cadmium and Selenium in both dosed group while, Cd+Se at low dose level caused no effect on serum testosterone concentration, while at high dose level Cd+Se treatment resulted in highly significant decrease in serum testosterone levels compared to control. Serum estradiole levels was significantly decreased in both low and high dosed groups by all treatments. In the present study, serum LHRH concentration was highly significantly increased by Cadmium and Cd+Se treatment in both low and high dosed groups compared to control, while Selenium treatment in both doses caused no effect on serum LHRH levels. Cadmium exposure at low dose level did not influenced mean serum level of LH significantly but at high dose mean serum LH level was decreased highly significantly. Selenium treatment in present experiment showed no alteration in mean serum LH level at low dose level but significant reduction in this gonadotropin serum level was noticed in high dose group. Cd+Se treatment at low dose level caused significant elevation in serum LH levels and significant decrease was noticed due to this treatment in high dosed group. In the current research, serum FSH level was not significantly effected by all three treatments in low dosed groups but in high dosed groups, serum FSH level was significantly decreased by Cadmium and Selenium individual treatments and no difference was observed in serum FSH level in Cd+Se treated group compared to control. In this investigation, epididymis caput and corpus tubule diameter was significantly decreased by Cadmium, Selenium and Cd+Se treatments compared to control in both low and high dosed groups. Cadmium, Selenium and Cd+Se treatments in high dosed groups caused significant increase in caput epithelial height compared to control. Epithelial height in corpus was significantly increased by all treatments in both low and high dosed experiments. In cauda epididymis, tubule diameter was decreased by Cadmium and Cd+Se treatment in both low and high dosed groups but individual treatment of Selenium resulted in significant increase in tubule diameter in both high and low dosed experiments. Epithelial height in cauda epididymis was significantly increased by individual treatment of Cadmium and decreased by Selenium while Cd+Se caused no effect compared to control in low dosed group. In high dosed group, Cadmium, Selenium and Cd+Se caused significant increase in cauda epithelial height compared to control. DNA status in epididymal sperm was analysed by single cell gell electrophosis. Comet length, comet height and head diameter was significantly increased by xix Abstract Cadmium, Selenium and Cd+Se treatment compared to control. %DNA in head, tail length, %DNA in tail, tail moment and olive moment were not effected by all the treatments at this dose level. In high dosed experiment, Cadmium treatment resulted in significant reduction in %DNA in head and significant increase in %DNA in tail, tail moment and olive moment. Selenium treatment at this dose level caused highly increased comet length, comet height, head diameter, tail length and decrease in olive moment compared to control. Cd+Se treatment resulted in significant increase in tail moment and reduction in olive moment compared to control. Concluding, at low dose level all treatments effected sperm DNA but the increase in comet length, comet height and head diameter by Selenium treatment was more pronounced. In high dosed group, highest effect of Cadmium treatment on %DNA in head, %DNA in tail, tail moment and olive moment was noticed. Vas deferens diameter and muscular thickness was significantly reduced by Cadmium, Selenium and Cd+Se treatments in both low and high dosed groups, whereas vas deferens epithelial height was increased by individual treatment of Cadmium and Selenium treatments in low dosed group. In high dosed group, epithelial height of vas deferens was increased by Cadmium and Cd+Se treatments compared to control. In the present study in both low and high dosed groups, dose dependent increase in Cadmium deposition was noticed in testes, epididymus and vas deferens of Cadmium and Cd+Se treated groups compared to control. In the present study, Selenium level was significantly increased in testes of Cadmium, Selenium and Cd+Se treated groups in low dose experiment, while high Selenium deposition was observed in testes of Cadmium and Selenium treated groups compared to control in high dose experiment with no effect in Cd+Se treated group in Selenium testicular levels at high dose level. However the highest deposition of Selenium was noticed in Selenium treated group of low dose experiment. In epididymis significantly high deposition of Selenium was noticed in Selenium and Cd+Se treated groups of low dose experiment whereas in high dose experiment significantly higher deposition of Selenium was obvious in epididymis of only Selenium treated group compared to control. Highest deposition was noticed in epididymis of high dosed Selenium group. Significantly high Selenium concentration was found in vas deferens of Selenium treated group at low dose level compared to control while in high dose experiment, significantly high levels of Selenium was deposited in Cadmium, Selenium and Cd+Se treated groups. Concluding, Cadmium act as reproductive toxicants in this study either given alone or in combination for 28 alternate days to adult rat. Cadmium treatments altered the function and structure of testes, epididymes and vas deferens adjusted through changed levels of serum gonadotrophins, estradioled and testosterone, eventually effecting the fertility status in male. This study also disclosed that both chemicals have toxic effects on sperm DNA integrity.