Impact of Early Arsenic Exposure on the Mineral Content and Oxidative Status of the Liver and Kidney of Pubescent and Adult Rats.

This study evaluated the effect of prepubertal arsenic exposure in the liver and kidney of pubescent rats and their reversibility 30 days after arsenic withdrawal. Male pups of Wistar rats (21 days old) were divided into two groups (n = 20/group): control animals received filtered water, and exposed rats received 10 mg L-1 arsenic from postnatal day (PND) 21 to PND 51. The liver and kidney of 52 days old rats (n = 10/group) were examined to investigate the effects of arsenic on micromineral content, antioxidant enzyme activity, histology, and biochemistry parameters. The other animals were kept alive under free arsenic conditions until 82 days old and further analyzed by the same parameters. Our results revealed that 52-day-old rats increased arsenic content in their liver and arsenic and manganese in their kidney. In those animals, glycogen and zinc content and catalase activity were reduced in the liver, and the selenium content decreased in the kidney. Thirty days later, arsenic reduced the manganese and iron content and SOD and CAT activity in the liver of 82-day-old rats previously exposed to arsenic, while glycogen and selenium content decreased in their kidney. In contrast, PND 82 rats exhibited higher retention of copper in the liver, an increase in iron and copper content, and CAT and GST activity in the kidney. Significant histological alterations of liver and kidney tissues were not observed in rats of both ages. We conclude that arsenic-induced toxicity could alter differently the oxidative status and balance of trace elements in pubertal and adult rats, demonstrating that the metalloid can cause effects in adulthood.

Long-term reproductive effects in male rats prenatally exposed to sodium arsenite.

Arsenic is an environmental toxicant known to be a carcinogen and endocrine disruptor. Maternal exposure to arsenic has been associated with fetus malformation and reproductive disorders in male offspring. However, it is unclear the extent to which those effects remain during postnatal development and adulthood. Therefore, this study aimed to investigate the long-term effects of prenatal arsenic exposure on reproductive parameters of male offspring at peripubertal and adult periods. Pregnant female Wistar rats were exposed to 0 or 10 mg/L sodium arsenite in drinking water from gestational day 1 (GD 1) until GD 21 and male pups were analyzed at postnatal day 44 (PND 44) and PND 70. We observed that some reproductive parameters were affected differently by arsenic exposure at each age evaluated. The body and reproductive organs weights, as well as testicular and epididymal morphology were strongly affected in peripubertal animals and recovered at adult period. On the other hand, the antioxidant genes expression (SOD1, SOD2, CAT and GSTK1) and the endogenous antioxidant system were affected in the testes and epididymides from both peripubertal and adult rats. Finally, an impairment in daily sperm production and in sperm parameters was observed in adult animals. Taken together, our findings show that prenatal arsenic exposure affected reproductive parameters of peripubertal and adult male rats mainly due to oxidative stress. Collectively, those alterations may be affecting fertility potential of adult animals.

Prepubertal arsenic exposure alters phosphoproteins profile, quality, and fertility of epididymal spermatozoa in sexually mature rats.

Arsenic intoxication affects male reproductive parameters of prepubertal rats. Besides, morphological and functional alterations in their testis and epididymis may remain after withdrawal of arsenic insult, causing potential impairment in male fertility during adulthood. In this study, we aimed at analyzing the effect of prepubertal arsenic exposure on the fecundity of epididymal sperm from sexually mature Wistar rats, assessing fertility indexes, sperm parameters, and sperm phosphoproteins content. Male pups on postnatal day (PND) 21 received filtered water (controls, n = 10) and 10 mg L-1 arsenite (n = 10) daily for 30 days. From PND52 to PND81, rats from both groups received filtered water. During this period, the males mated with non-exposed females between PND72 and PND75. Our results showed that sexually mature rats presented low sperm production, epididymal sperm count, motility, and quality after prepubertal arsenic exposure. These findings possibly contributed to the low fertility potential and high preimplantation loss. Epididymal sperm proteome detected 268 proteins, which 170 were found in animals from both control and arsenic groups, 27 proteins were detected only in control animals and 71 proteins only in arsenic-exposed rats. In these animals, SPATA 18 and other five proteins were upregulated, whereas keratin type II cytoskeletal 1 was downregulated (q < 0.1). The results of KEGG pathway analysis demonstrated an enrichment of pathways related to dopaminergic response, adrenergic signaling, protein degradation, and oocyte meiosis in arsenic-exposed animals. Moreover, 26 proteins were identified by phosphoproteomic with different phosphorylation pattern in animals from both groups, but SPATA18 was phosphorylated only in arsenic-exposed animals. We concluded that prepubertal exposure to arsenic is deleterious to sperm quality and male fertility, altering the sperm phosphoproteins profile.

Impact of prenatal arsenic exposure on the testes and epididymides of prepubertal rats.

Arsenic is a pollutant widely found in the environment due to natural and anthropogenic sources. Exposure to arsenic forms in drinking water has been related with male reproductive dysfunctions in humans and experimental animals at adult age. However, the impact of this pollutant on postnatal reproductive development of male offspring exposed in utero to arsenic is still unknown. Therefore, this study aimed to investigate the effects of prenatal arsenic exposure on the postnatal development of the testes and epididymides of rats, during prepuberty. For this purpose, pregnant female Wistar rats were provided drinking water containing 0 or 10 mg/L sodium arsenite (AsNaO2) from gestational day 1 (GD 1) until GD 21 and the male offspring was evaluated in different periods of prepuberty. Our results showed that prenatal arsenic exposure affected the initial sexual development of male pups, reducing their body weight and relative anogenital distance at postnatal day 1. At different periods of prepuberty, male pups from arsenic exposed dams showed a reduction of body and reproductive organs weights, testosterone levels and testis morphometric parameters. Moreover, these pups presented changes in the expression of SOD1, SOD2, CAT and GSTK1 genes and in the activity of superoxide dismutase, catalase and glutathione s-transferase in the testes and epididymides during prepuberty. Taken together, our results show that prenatal arsenic exposure provoked reproductive disorders in prepubertal male rats, probably due to reproductive reprograming and oxidative stress induced by this pollutant.

Prepubertal exposure to arsenic alters male reproductive parameters in pubertal and adult rats.

Arsenic induces reproductive disorders in pubertal males after prepubertal exposure. However, it is unclear the extent to which those effects remain in testis and epididymis of sexually mature rats after arsenic insult. This study evaluated the effects of prepubertal arsenic exposure in male organs of pubertal rats, and their reversibility in adult rats. Male pups of Wistar rats on postnatal day (PND) 21 were divided into two groups (n = 20/group): Control animals received filtered water and exposed rats received 10 mg L--1 arsenic from PND 21 to PND 51. At PND 52, testis and epididymis of ten animals per group were examined for toxic effects under morphological, functional, and molecular approaches. The other animals were kept alive under free arsenic conditions until PND 82, and further analyzed for the same parameters. Pubertal rats overexpressed mRNA levels of SOD1, SOD2, CAT, GSTK1, and MT1 in their testis and SOD1, CAT, and GSTK1 in their epididymis. In those organs, catalase activity was altered, generating byproducts of oxidative stress. The antioxidant gene expression was unchanged in adult rats in contrast to the altered activity of antioxidant enzymes. Histological alterations of testis and epididymis tissues were observed in pubertal and adult rats. Interestingly, only adult rats exhibited a remarkable decrease in serum testosterone levels. Prepubertal exposure to arsenic caused morphological and functional alterations in male reproductive organs of pubertal rats. In adult rats, these damages disappeared, remained, get worsened, or recovered depending on the parameter analyzed, indicating potential male fertility disorders during adulthood.