title: Bisphenol A impairs insulin signaling and glucose homeostasis and decreases steroidogenesis in rat testis: an in vivo and in silico study.
abstract: Bisphenol A (BPA) is a potential endocrine disruptor and testicular toxicant. Recently, we have reported that exposure to BPA increases plasma insulin and glucose levels and decreases the levels of glycolytic enzymes, glucose transporter-8 (GLUT-8) and insulin receptor substrate-2 (IRS-2) in rat testis. In the present study we sought to investigate the effects of low doses of BPA on insulin signaling molecules, glucose transporter-2 (GLUT-2) and steroidogenesis in rat testis. BPA was administered to rats by oral gavage at doses of 0.005, 0.5, 50 and 500 μg/kg body weight/day for 45 days. A positive control was maintained by administering 17-β-estradiol (50 μg/kg body weight/day). Decreased levels of insulin, insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phosphoinositide 3-kinase (PI-3 kinase) and GLUT-2 were observed in rat testis following BPA administration. Dose-dependent decrease in the activities of antioxidant enzymes, 3-β-hydroxysteroid dehydrogenase (3β-HSD), 17-β-hydroxysteroid dehydrogenase (17β-HSD), Steroidogenic Acute Regulatory Protein (StAR) and testosterone were also observed. Molecular docking of BPA, 17-β-estradiol, cytochalasin B and glucose with GLUT-2 and GLUT-8 revealed the higher binding affinity of BPA with GLUT-2 and GLUT-8. Thus, BPA impairs insulin signaling and glucose transport in rat testis which could consequently lead to impairment of testicular functions.
authors.affiliation: Department of Biochemistry & Molecular Biology, Center for Bioinformatics, School of Life Sciences, Pondicherry University, Pondicherry 605014, India.
authors.forename: Shereen Cynthia
authors.initials: SC
authors.lastname: D'Cruz
authors.forename: Rajamanickam
authors.initials: R
authors.lastname: Jubendradass
authors.forename: Mannu
authors.initials: M
authors.lastname: Jayakanthan
authors.forename: Sivaraj Judith Amala
authors.initials: SJ
authors.lastname: Rani
authors.forename: Premendu Prakash
authors.initials: PP
authors.lastname: Mathur
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D002374:Catalase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D007328:Insulin / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D013256:Steroids / Q000096:biosynthesis*; D013482:Superoxide Dismutase / Q000378:metabolism; D013737:Testis / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D002374:Catalase; D005947:Glucose; D051246:Glucose Transport Proteins, Facilitative; D051273:Glucose Transporter Type 2; D007328:Insulin; D010636:Phenols; D013256:Steroids; D013482:Superoxide Dismutase; C495683:Slc2a2 protein, rat; C498629:Slc2a8 protein, rat; C006780:bisphenol A; D000098826:Bisphenol A Compounds