Chronic exposure to low dose of bisphenol A impacts on the first round of spermatogenesis via SIRT1 modulation

• Published in: Scientific reports Vol. 8; no. 1; pp. 2961 - 12
• Main Authors: Chianese, Rosanna, Viggiano, Andrea, Urbanek, Konrad, Cappetta, Donato, Troisi, Jacopo, Scafuro, Marika, Guida, Maurizio, Esposito, Grazia, Ciuffreda, Loreta Pia, Rossi, Francesco, Berrino, Liberato, Fasano, Silvia, Pierantoni, Riccardo, De Angelis, Antonella, Meccariello, Rosaria
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.02.2018; Nature Publishing Group
• Subjects: 13/2; 14; 14/19; 38; 631/443/494; 692/163/2743; 82; 82/58; Animals; Apoptosis; Apoptosis - drug effects; Autocrine signalling; Benzhydryl Compounds - blood; Benzhydryl Compounds - toxicity; Bisphenol A; Body weight; Body Weight - drug effects; Body weight gain; Chronic exposure; Contaminants; DNA Damage; Dose-Response Relationship, Drug; Down-Regulation - drug effects; Drinking water; Endocrine disruptors; Energy balance; Energy metabolism; Epoxy resins; Estrogens; Female; Gene Expression Regulation, Enzymologic - drug effects; Homeostasis; Humanities and Social Sciences; Hypothalamus; Lactation; Male; multidisciplinary; NAD; Offspring; Oxidative metabolism; Oxidative stress; Oxidative Stress - drug effects; Paracrine signalling; Phenols - blood; Phenols - toxicity; Pituitary; Placenta; Polycarbonate; Rats; Rats, Wistar; Reactive oxygen species; Science; Science (multidisciplinary); SIRT1 protein; Sirtuin 1 - metabolism; Spermatogenesis; Spermatogenesis - drug effects; Testis - drug effects; Testis - metabolism; Testis - physiology; Time Factors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-21076-8

Spermatogenesis depends on endocrine, autocrine and paracrine communications along the hypothalamus-pituitary-gonad axis. Bisphenol A (BPA), an estrogen-mimic endocrine disrupting chemical, is an environmental contaminant used to manufacture polycarbonate plastics and epoxy resins with toxic effects for male reproduction. Here we investigated whether the chronic exposure to low BPA doses affects spermatogenesis through the modulation of SIRT1, a NAD + -dependent deacetylase involved in the progression of spermatogenesis, with outcomes on apoptosis, oxidative stress, metabolism and energy homeostasis. BPA exposure via placenta first, and lactation and drinking water later, affected the body weight gain in male offspring at 45 postnatal days and the first round of spermatogenesis, with impairment of blood testis barrier, reactive oxygen species production, DNA damage and decreased expression of SIRT1. The analysis of SIRT1 downstream molecular pathways revealed the increase of acetyl-p53 Lys370 , γH2AX foci, the decrease of oxidative stress defenses and the higher apoptotic rate in the testis of treated animals, with partial rescue at sex maturation. In conclusion, SIRT1 pathways disruption after BPA exposure can have serious consequences on the first round of spermatogenesis.