Prepubertal exposure to low doses of sodium arsenite impairs spermatogenesis and epididymal histophysiology in rats

Abstract

For the first time, juvenile toxicity of inorganic arsenic (As) was investigated in male rats, focusing on reproductive effects. As is a metalloid naturally occurring in the environment, being the inorganic forms the most toxics. Contaminated drinking water and agricultural products are the main prospectors of intoxication for general population. In the present study, Wistar male rats (21 days old) were distributed into three groups (n = 10/group): control (received vehiclefiltered drinking water), As1 (received AsNaO 2 at 0.01 mg L −1 ) and As2 (received AsNaO 2 at 10 mg L −1 ). The animals were euthanized on PND 53. Testicular damages increased in As1 and As2 compared to control (ie, presence of vacuolization, acidophilic cells, and epithelium degeneration). Testicular interstitium of As1 and As2 presented fluid's increase and intense inflammatory infiltration. In the epididymis there was reduction of sperm amount in the lumen, besides epithelium areas presenting cribriform aspect in As1 and As2, exfoliation of cells in the light (in As1) and vacuoles (in As2). In epididymis interstitium, inflammatory infiltrates were observed in initial segment of As1 and As2. AsNaO 2 changed immunolabeling pattern for androgen receptor in epididymis of As2, although serum testosterone levels was statistically comparable to control. Mass spectrometry revealed higher As concentrations in testis and epididymis of As2 compared to As1 and Control. These results indicate compromise of spermatogenesis and epididymal histophysiology in AsNaO 2 -treated animals, possibly impairing sperm quality and fertility in long-term, even at low levels of exposure. Investigations about the reversibility of reproductive damages are necessary to better understand the mechanisms of As reproductive toxicity. K E Y W O R D Sexperimental study, histopathology, juvenile toxicity, metalloid 1 | INTRODUCTION Arsenic (As) is an element occurring naturally in the environment, chemically classified as metalloid. It can be found under organic and inorganic forms, being the inorganic the most toxic and prevalent in drinking water and aquatic environments. 1,2 The natural sources of As contamination in groundwater is often originated from the mobilization of natural deposits in rocks, sediments, soils, and geothermal water. 3 However, As contamination occurs mainly through a variety of anthropogenic activities, such as industry activity, copper smelting, As-bearing pesticides and herbicide and mining. 4 It is estimated that approximately 150 million people around the world are affected by increasing concentrations of As in drinking water. 5 In this concern, unintentional As exposure of populations from Bangladesh,

Low concentrations of sodium arsenite induce hepatotoxicity in prepubertal male rats

“…The absence of changes in body and organs weight of As ‐exposed animals indicates that As did not induce a systemic intoxication, possibly due to the use of low concentrations in the experimental conditions presented here. Likewise, no changes were observed in the weight of reproductive organs of male rats in a previous study performed in the same experimental conditions . Similarly, absence of systemic toxicity was also observed in a study with adult male rats exposed for 8 weeks to sodium arsenite at concentrations of 0.01 mg L −1 and 10 mg L −1 , corroborating our data, since the treated animals exhibited body weight comparable to control animals …”

“…In fact, according to the literature, arsenic accumulation in adult animals decreases according to the following order: kidney> liver> testis . Thus, based in present results, in addition to a previously published study, it is possible to infer that the retention of sodium arsenite in juvenile organisms follows the same pattern as observed in adult animals. The high concentration of As in the kidney can be explained by the methylation process, whose by‐product (dimethylarsinic acid) is partially reabsorbed by the renal tubules before being excreted by the urine.…”

“…Wistar male rats (21 days old) were supplied by CEDEME ‐ Center for Development of Experimental Models for Medicine and Biology, Federal University of São Paulo ‐ UNIFESP and housed as described by Medeiros and coauthors . All experimental procedures were in accordance with the ethical principles from the Animal Use Ethics Committee of UNIFESP (Protocol number 7200150216).…”

“…Left kidney and liver were fixed in buffered formaldehyde solution (10%) for 24 hours and lately transferred to 70% alcohol. The pieces were processed according to described by Medeiros et al for testis and epididymis …”

“…About 200 mg of samples (liver, kidney, and commercial ration) were destined to As determination through the same method described by Medeiros et al for testis and epididydmis …”