Arsenic aggravated reproductive toxicity in male rats exposed to lead during the perinatal period.

The aim of this study was to assess the reproductive toxic effects of arsenic on adult Wistar rats exposed to lead during the perinatal period. The pregnant rats were allowed ad libitum access to tap water containing 819 mg of lead (Pb) per L or without Pb from conception until weaning. Litter size, survival rate and developmental milestones of the pups delivered by Pb exposed dams were comparable to those of the control rats. Conversely, the pups exposed to Pb during the perinatal period exhibited significant delay in cliff avoidance, negative geotaxis, surface righting reflex, ascending wire mesh and testis descent. The control and perinatal Pb-exposed male rats were maintained on tap water containing 2.3 mg of arsenite (As) per L or without arsenite from the pubertal period (post-natal day 55) to adulthood (post-natal day 115) and assessed for reproductive end points. The results revealed that the (1) relative weights of the testis, epididymis, seminiferous tubules and ventral prostate; (2) daily sperm production; (3) epididymal sperm density and (4) numbers of motile, viable, and HOS tail swelled sperm declined significantly in the rats exposed to either Pb or As. The activity levels of testicular 3ß- and 17ß-hydroxysteroid dehydrogenases were also significantly decreased in the experimental rats. Significant elevation in the levels of reactive oxygen species and lipid peroxidation in association with reduced activities of antioxidant enzymes in the testis and different epididymal regions was recorded in the experimental rats. In the fertility study, although each male in the control and experimental groups produced a copulatory plug and impregnated a female, the mean conception time significantly increased in the experimental groups. The mean number of implantations decreased significantly in the females mated with the experimental males. Moreover, the results of the present study also indicate that reproductive alterations were more deteriorated in the Pb-exposed rats treated with arsenic when compared to individual exposures. In conclusion, the data clearly suggest that reproductive toxicity in male rats exposed to Pb during the perinatal period is exacerbated by As treatment during the pubertal period.

Alleviative effect of resveratrol on polyvinyl chloride-induced reproductive toxicity in male Wistar rats.

The present study was aimed to investigate the effect of PVC on reproductive competence in adult male Wistar rats. Further, the study also encompasses the protective effect of trans-resveratrol on PVC-induced reproductive toxicity in rats. Adult male rats weighing 210-240 g were administered with either PVC at two different doses 100 and 500 mg/kg body weight, orally, daily for 60 days or resveratrol (20 mg/kg body weight/day) through gavage for 60 days on alternate days or both PVC (500 mg/kg body weight) and resveratrol. The results revealed significant reduction in the weights of reproductive organs, epididymal sperm count, viable-, motile-, and HOS-tail coiled sperm and testicular daily sperm production, steroidogenic enzyme activities, serum testosterone levels in PVC treated rats. Conversely the levels of lipid peroxidation increased significantly with a decrease in activity levels of antioxidant enzymes in the testis of PVC exposed rats. Exposure to PVC resulted in reduction in epithelial thickness and seminiferous tubule diameter. No significant changes in the selected reproductive variables were observed in the resveratrol alone treated control rats, whereas, co-administration of resveratrol and PVC resulted in a significant improvement in steroidogenesis and spermatogenesis and mitigated oxidative stress over PVC exposed rats.

Altered spermatogenesis, steroidogenesis and suppressed fertility in adult male rats exposed to genistein, a non-steroidal phytoestrogen during embryonic development.

This article focuses on the effects of prenatal exposure to genistein on the mother, her pregnancy and reproductive functions of the male progeny, since these issues have ethological relevance in both animals and humans. Pregnant Wistar rats received i.p. injections of genistein at a dose level of 2, 20 or 100 mg/kg body weight daily from 12th to 19th day of gestation. Male pups from control and genistein exposed animals were weaned and allowed to develop until 100 days of age; however, when they were 90 days old, twelve males from each group were cohabited with untreated 90-day old females for 8 days. Results revealed a significant decrease in indices of reproductive organs in adult male rats exposed to genistein during embryonic development. Dose dependent reduction was observed in daily sperm production and epididymal sperm density and quality in genistein treated rats. Significant decrease was observed in the activity levels of 3ß- and 17ß-hydroxysteroid dehydrogenases in testis of experimental rats with a decline in plasma testosterone levels. Histological examination of testis of genistein treated rats indicated deterioration in testicular architecture. In the fertility study, the mean number of implantations and live fetuses per dam mated with 100 mg genistein exposed males was reduced.

Effects of maternal exposure to aflatoxin B1 during pregnancy on fertility output of dams and developmental, behavioral and reproductive consequences in female offspring using a rat model.

A suboptimal in utero environment can have detrimental effects on the pregnancy and long-term adverse "programing" effects on the offspring. Aflatoxin B1 is one of the potent reproductive toxicants and currently detected in both milk and tissues. This article focuses on the effects of prenatal exposure to graded doses of aflatoxin B1 on the pregnancy outcomes of dams and postnatal developments of the female offspring, since these issues have ethological relevance in both animals and humans. Pregnant Wistar rats were injected intramuscularly with vehicle or aflatoxin B1 (10, 20, 50 or 100 µg/kg body weight/day) on days 12-19 of gestation. At parturition, newborns were observed for clinical signs of toxicity and survival. The female offspring were examined through a battery of tests in order to evaluate their developmental, behavioral and reproductive end points. All animals were born alive. The litter size of the aflatoxin B1 treated rats was comparable to the controls. However, the birth weight of the pups in the experimental group was significantly lower when compared to controls. Significant and persistent lags in cliff avoidance, negative geotaxis, surface rightening activity and ascending wire mesh, with a delay in elapsed time for vaginal opening were detected in the female progeny exposed to aflatoxin B1 during embryonic development. The locomotor activity and exploratory behavior in experimental females were significantly decreased than that of controls. Embryonic exposure to aflatoxin B1 also resulted in prolonged stress response, irregular estrus and suppressed fertility output in the progeny at their adulthood. These results indicate that in utero exposure to aflatoxin B1 severely compromised postnatal development of neonatal rats and caused irregular estrus that was accompanied by suppressed fertility output.

Prenatal exposure to aflatoxin B1: developmental, behavioral, and reproductive alterations in male rats.

Previous studies have shown that aflatoxin B1 (AfB1) inhibits androgen biosynthesis as a result of its ability to form a high-affinity complex with the steroidogenic acute regulatory protein. The results of the present study demonstrate the postnatal effects of in utero exposure to AfB1 in the rat. Pregnant Wistar rats were given 10, 20, or 50 µg AfB1/kg body weight daily from gestation day (GD) 12 to GD 19. At parturition, newborns were observed for clinical signs and survival. All animals were born alive and initially appeared to be active. Male pups from control and AfB1-exposed animals were weaned and maintained up to postnatal day (PD) 100. Litter size, birth weight, sex ratio, survival rate, and crown-rump length of the pups were significantly decreased in AfB1-exposed rats when compared to controls. Elapsed time (days) for testes to descend into the scrotal sac was significantly delayed in experimental pups when compared to control pups. Behavioral observations such as cliff avoidance, negative geotaxis, surface rightening activity, ascending wire mesh, open field behavior, and exploratory and locomotory activities were significantly impaired in experimental pups. Body weights and the indices of testis, cauda epididymis, prostate, seminal vesicles, and liver were significantly reduced on PD 100 in male rats exposed to AfB1 during embryonic development when compared with controls. Significant reduction in the testicular daily sperm production, epididymal sperm count, and number of viable, motile, and hypo-osmotic tail coiled sperm was observed in experimental rats. The levels of serum testosterone and activity levels of testicular hydroxysteroid dehydrogenases were significantly decreased in a dose-dependent manner with a significant increase in the serum follicle-stimulating hormone and luteinizing hormone in experimental rats. Deterioration in the testicular and cauda epididymal architecture was observed in experimental rats. The results of fertility studies revealed a significant decrease in the mating index in experimental rats with an increase in the pre- and post-implantation losses in rats mated with prenatal AfB1-exposed males, indicating poor male reproductive performance. These results indicate that in utero exposure to AfB1 severely compromised postnatal development of neonatal rats, and caused a delay in testes descent and reduction in steroidogenesis and spermatogenesis that were accomplished by suppressed reproduction at adulthood.

Aflatoxin B1-Induced Reproductive Toxicity in Male Rats: Possible Mechanism of Action.

Aflatoxin B1 (AFB1), one of the most common mycotoxins found in human foods, is principally hepatotoxic; however, it also affects reproduction. The aim of the present study was to elucidate the reproductive toxic effects and possible mechanism of action of AFB1 in rats. Male Wistar rats were injected intramuscularly with doses of 10, 20, or 50 µg AFB1/kg body weight on alternate days from 45 to 100 days of age. Significant reductions in body weights, relative weights of reproductive organs, daily sperm production, epididymal sperm count, viable sperm, motile sperm, and hypoosmotic swelling-tail coiled sperm were observed. Significant decreases in testicular steroidogenic enzymes and serum testosterone levels were also observed indicating decreased steroidogenesis. In silico docking studies illustrated AFB1 binds with steroidogenic acute regulatory (StAR) protein thereby affecting the transport of cholesterol into mitochondria resulting in decreased steroidogenesis.

Protective effects of N-acetylcysteine against arsenic-induced oxidative stress and reprotoxicity in male mice.

Arsenic is a well-known environmental toxic metalloid element and carcinogen that affects multiple organ systems including tissue lipid peroxidation and reproduction. The present study was aimed to investigate the protective role of N-acetylcysteine (NAC) on arsenic-induced testicular oxidative damage and antioxidant and steroidogeneic enzymes and sperm parameters in mice. Arsenic was administered through drinking water to mice at a concentration of 4.0 ppm sodium arsenite (actual concentration 2.3 ppm arsenic) for 35 days. The body weight of treated mice did not show significant change as compared with the control mice. In arsenic exposed mice there was a significant decrease in the weight of the testis, epididymis and prostate gland as compared with the control animals. Significant reduction was observed in epididymal sperm count, motile sperms and viable sperms in mice exposed to arsenic indicate decreased spermatogenesis and poor sperm quality. The activity levels of testicular 3ß- and 17ß-hydroxysteroid dehydrogenases and circulatory levels of testosterone were also decreased in arsenic treated mice indicating reduced steroidogenesis. A significant increase in the activities of lipid peroxidation and a significant decrease in the activities of antioxidant enzymes were observed in the testis of mice exposed to arsenic. In addition, significant increase in the testicular arsenic levels was observed during arsenic intoxication. No significant changes in the oxidation status and selected reproductive variables were observed in the N-acetylcysteine alone treated mice. Whereas, intra-peritoneal injection of NAC to arsenic exposed mice showed a significant increase in the weights of reproductive organs, reduction in arsenic-induced oxidative stress in the tissues and improvement in steroidogenesis over arsenic-exposed mice indicating the beneficial role of N-acetylcysteine to counteract arsenic-induced oxidative stress and to restore the suppressed reproduction in male mice.

Protective role of Centella asiatica on lead-induced oxidative stress and suppressed reproductive health in male rats.

Centella asiatica has been mentioned in ancient ayurvedic text of the Indian system of medicine for its properties to promote intelligence. The objective of the present study was to investigate the beneficial effects of C. asiatica on lead-induced oxidative stress and suppressed reproductive performance in male rats. Significant decrease in the weights of testes and epididymis were observed in lead treated animals. Exposure to lead acetate significantly increased malondialdehyde levels with a significant decrease in the superoxide dismutase and catalase activities in the liver, brain, kidneys and testes of rats. Epididymal sperm count, viable sperms, motile sperms and HOS-tail coiled sperms decreased significantly in lead-exposed rats. Testicular steroidogenic enzyme activities also decreased significantly in lead-exposed rats. No significant changes in the selected reproductive variables were observed in the plant extract alone treated rats. Whereas, co-administration of aqueous extracts of C. asiatica to lead exposed rats showed a significant increase in the weights of reproductive organs, reduction in lead-induced oxidative stress in the tissues and improvement in selected reproductive parameters over lead-exposed rats indicating the beneficial role of C. asiatica to counteract lead-induced oxidative stress and to restore the suppressed reproduction in male rats.