Transient Gestational Exposure to Hexavalent Chromium (CrVI) Adversely Affects Testicular Differentiation: A Study in Rat Model

Chromium (Cr), an essential trace element, turns into an endocrine disruptor and male reproductive toxicant when its concentration in drinking water exceeds the safe limit. Improper disposal of effluents from more than 50 industries that use Cr contaminate the environment, in addition to occupational exposure of the workers. Testis has come to stay as a target for the reproductive toxicity of hexavalent Cr (CrVI), whereas its impact on fetal testicular differentiation remains elusive. We tested the hypothesis “In utero exposure to CrVI may alter the level of specific proteins controlling differentiation of testicular cell types”. Pregnant Wistar rats were exposed to drinking water containing 50, 100 and 200 ppm potassium dichromate (CrVI) during gestational days 14 to 21, covering the period of fetal differentiation of testicular cells. Testes were collected on postnatal day 1 and subjected to light microscopic histological studies and immunohistochemical detection of cell-specific proteins. Testis of neonatal rats with gestational exposure to high doses of CrVI showed shrunken and dispersed tubules with fewer gonocytes, extensive vacuolization of seminiferous cord accompanied by damaged epithelium, and shrunken Leydig cells present in large interstitial spaces and loose compaction of cells when compared coeval control group. Immunosignals of androgen and estrogen receptor β increased, whereas those of estrogen receptor α, follicle stimulating hormone receptor, anti-Mullerian hormone, P450 aromatase, inhibin, c-fos and c-jun decreased. Immunosignals of steroidogenic acute regulatory protein and CYP11A1 increased, whereas 3β - hydroxy steroid dehydrogenase and CYP17A1 proteins decreased, indicating compromised steroidogenic function. Our findings support the proposed hypothesis and we conclude that gestational exposure to CrVI disrupts specific hormones and hormone receptors that control fetal differentiation of testicular cells. The detrimental effect of gest