Low doses of Bisphenol S affect post-translational modifications of sperm proteins in male mice

• Published in: Reproductive biology and endocrinology Vol. 18; no. 1; pp. 56 - 10
• Main Authors: Řimnáčová, Hedvika, Štiavnická, Miriam, Moravec, Jiří, Chemek, Marouane, Kolinko, Yaroslav, García-Álvarez, Olga, Mouton, Peter R, Trejo, Azalia Mariel Carranza, Fenclová, Tereza, Eretová, Nikola, Hošek, Petr, Klein, Pavel, Králíčková, Milena, Petr, Jaroslav, Nevoral, Jan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 28-05-2020; BioMed Central; BMC
• Subjects: Acetylation; Acetylation - drug effects; Animals; Antibodies; Bisphenol A; Bisphenol S; Body weight; Chromatin; DNA damage; DNA Damage - drug effects; DNA methylation; Dose-Response Relationship, Drug; Drinking water; Endocrine disruptor; Endocrine disruptors; Endocrine Disruptors - pharmacology; Epigenesis, Genetic; Epigenetic inheritance; Epoxy resins; Experiments; Health aspects; Histochemistry; Liquid chromatography; Low dose effect; Lysine; Male; Male reproduction; Mass spectroscopy; Mice; Motility; Phenols - pharmacology; Phosphorylation - drug effects; Polycarbonates; Post-translation; Post-translational modification; Post-translational modifications; Protein Processing, Post-Translational - drug effects; Proteins; Risk assessment; Software; Sperm; Sperm Maturation - drug effects; Spermatogenesis; Spermatozoa - drug effects; Sulfones - pharmacology; Testes; Testis - drug effects; Testis - pathology; Tyrosine; Variance analysis; Czech Republic; United Kingdom > UK; United States > US; Germany; Post-translational modification; Endocrine disruptor; Low dose effect; Male reproduction; Bisphenol S
• ISSN: 1477-7827; 1477-7827
• DOI: 10.1186/s12958-020-00596-x

Bisphenol S (BPS) is increasingly used as a replacement for bisphenol A in the manufacture of products containing polycarbonates and epoxy resins. However, further studies of BPS exposure are needed for the assessment of health risks to humans. In this study we assessed the potential harmfulness of low-dose BPS on reproduction in male mice.
To simulate human exposure under experimental conditions, 8-week-old outbred ICR male mice received 8 weeks of drinking water containing a broad range of BPS doses [0.001, 1.0, or 100 μg/kg body weight (bw)/day, BPS1-3] or vehicle control. Mice were sacrificed and testicular tissue taken for histological analysis and protein identification by nano-liquid chromatography/mass spectrometry (MS) and sperm collected for immunodetection of acetylated lysine and phosphorylated tyrosine followed by protein characterisation using matrix-assisted laser desorption ionisation time-of-flight MS (MALDI-TOF MS).
The results indicate that compared to vehicle, 100 μg/kg/day exposure (BPS3) leads to 1) significant histopathology in testicular tissue; and, 2) higher levels of the histone protein γH2AX, a reliable marker of DNA damage. There were fewer mature spermatozoa in the germ layer in the experimental group treated with 1 μg/kg bw (BPS2). Finally, western blot and MALDI-TOF MS studies showed significant alterations in the sperm acetylome and phosphorylome in mice treated with the lowest exposure (0.001 μg/kg/day; BPS1), although the dose is several times lower than what has been published so far.
In summary, this range of qualitative and quantitative findings in young male mice raise the possibility that very low doses of BPS may impair mammalian reproduction through epigenetic modifications of sperm proteins.