Department of Endocrinology, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Taramani-Velachery Link Road, Chennai, 600113, Tamil Nadu, India; Department of Veterinary Integrative Biosciences, College of Veterinary Medicine & Biomedical Sciences, TAMU-4458, Texas A&M University, College Station, TX, 77843, USA.
Department of Endocrinology, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Taramani-Velachery Link Road, Chennai, 600113, Tamil Nadu, India.
Reprod Toxicol. 2021 Apr;101:63-73. doi: 10.1016/j.reprotox.2021.01.014. Epub 2021 Mar 3.
We have reported sub-fertility in F progeny rats with gestational exposure to hexavalent chromium [Cr(VI)], which had disrupted Sertoli cell (SC) structure and function, and decreased testosterone (T). However, the underlying mechanism for reduced T remains to be understood. We tested the hypothesis "transient prenatal exposure to Cr(VI) affects testicular steroidogenesis by altering hormone receptors and steroidogenic enzyme proteins in Leydig cells (LCs)." Pregnant Wistar rats were given drinking water containing 50, 100, and 200 mg/L potassium dichromate during gestational days 9-14, encompassing fetal differentiation window of the testis from the bipotential gonad. F male rats were euthanized on postnatal day 60 (peripubertal rats with adult-type LCs alone). Results showed that prenatal exposure to Cr(VI): (i) increased accumulation of Cr(III) in the testis of F rats; (ii) increased serum levels of luteinizing and follicle stimulating hormones (LH and FSH), and 17β estradiol, and decreased prolactin and T; (iii) decreased steroidogenic acute regulatory protein, cytochrome P450 11A1, cytochrome P450 17A1, 3β- and 17β-hydroxysteroid dehydrogenases, cytochrome P450 aromatase and 5α reductase proteins, (iv) decreased specific activities of 3β and 17β hydroxysteroid dehydrogenases; (v) decreased receptors of LH, androgen and estrogen in LCs; (vi) decreased 5α reductase and receptor proteins of FSH, androgen, and estrogen in SCs. The current study concludes that prenatal exposure to Cr(VI) disrupts testicular steroidogenesis in F progeny by repressing hormone receptors and key proteins of the steroidogenic pathway in LCs and SCs.
我们曾报道过，六价铬（Cr(VI)）会使子代雄性大鼠生育力下降，导致其睾丸支持细胞（Sertoli cell，SC）结构和功能受损，同时降低睾酮（Testosterone，T）水平。然而，T 降低的潜在机制仍不清楚。我们提出假设：“孕期短暂接触 Cr(VI)会通过改变睾丸间质细胞（Leydig cell，LC）中的激素受体和类固醇生成酶蛋白，从而影响睾丸类固醇生成”。我们给妊娠 Wistar 大鼠饮用含 50、100 和 200mg/L 重铬酸钾的水，持续至妊娠第 9-14 天，此时正是雄性胎儿睾丸从双潜能性腺分化的关键时期。雄性子代大鼠在出生后 60 天（接近青春期的大鼠，仅存在成人型 LC）被安乐死。结果显示，孕期接触 Cr(VI)：（i）增加了 F 代大鼠睾丸中 Cr(III)的积累；（ii）增加了血清黄体生成素（Luteinizing Hormone，LH）、卵泡刺激素（Follicle Stimulating Hormone，FSH）、17β 雌二醇水平，降低了催乳素（Prolactin）和 T 水平；（iii）降低了类固醇生成急性调节蛋白（StAR）、细胞色素 P45011A1、细胞色素 P45017A1、3β-和 17β-羟甾脱氢酶、细胞色素 P450 芳香化酶和 5α 还原酶的蛋白水平；（iv）降低了 3β-和 17β-羟甾脱氢酶的比活性；（v）降低了 LC 中 LH、雄激素和雌激素受体；（vi）降低了 SC 中 FSH、雄激素和雌激素的 5α 还原酶和受体蛋白水平。本研究表明，孕期接触 Cr(VI)通过抑制 LC 和 SC 中的激素受体和类固醇生成途径中的关键蛋白，破坏了 F 代雄性大鼠的睾丸类固醇生成。
