Unexpected Interacting Effects of Physical (Radiation) and Chemical (Bisphenol A) Treatments on Male Reproductive Functions in Mice

Abstract

For decades, numerous chemical pollutants have been described to interfere with endogenous hormone metabolism/signaling altering reproductive functions. Among these endocrine disrupting substances, Bisphenol A (BPA), a widely used compound, is known to negatively impact germ and somatic cells in the testis. Physical agents, such as ionizing radiation, were also described to perturb spermatogenesis. Despite the fact that we are constantly exposed to numerous environmental chemical and physical compounds, very few studies explore the impact of combined exposure to chemical and physical pollutants on reproductive health. The aim of this study was to describe the impact of fetal co-exposure to BPA and IR on testicular function in mice. We exposed pregnant mice to 10 µM BPA (corresponding to 0.5 mg/kg/day) in drinking water from 10.5 dpc until birth, and we irradiated mice with 0.2 Gy (γ-ray, RAD) at 12.5 days post-conception. Co-exposure to BPA and γ-ray induces DNA damage in fetal germ cells in an additive manner, leading to a long-lasting decrease in germ cell abundance. We also observed significant alteration of adult steroidogenesis by RAD exposure independently of the BPA exposure. This is illustrated by the downregulation of steroidogenic genes and the decrease of the number of adult Leydig cells. As a consequence, courtship behavior is modified, and male ultrasonic vocalizations associated with courtship decreased. In conclusion, this study provides evidence for the importance of broadening the concept of endocrine disruptors to include physical agents, leading to a reevaluation of risk management and regulatory decisions.

Cocktails of NSAIDs and 17α Ethinylestradiol at Environmentally Relevant Doses in Drinking Water Alter Puberty Onset in Mice Intergenerationally

“…Comparison of these DEGs with those identified after exposure to other EDCs indicated that 1 to 17 DEGs detected in F1 testes were also deregulated after exposure to the xenoestrogens bisphenol A (BPA) [ 86 ] and EE2 [ 87 ] and to the anti-androgenic EDCs di-2-ethylhexyl phthalate (DEHP) [ 88 ], DDT, and vinclozolin [ 89 ] ( Supplementary Table S9 ). Some genes that were also differentially expressed in F2 testes might be biomarkers of exposure to estrogenic ( Actn3 , Cntnap5b, Kcnk2 , Sall1 ) or anti-androgenic ( Dhrs4 , Fabp3 ) compounds.…”

Knowledge Gap in Understanding the Steroidogenic Acute Regulatory Protein Regulation in Steroidogenesis Following Exposure to Bisphenol A and Its Analogues

“…Furthermore, serum testosterone levels were also found to be significantly lower in BPA-treated mice at a dose of 20 mg/kg after 7 days of exposure [ 77 ]. StAR gene expression was found to be downregulated in embryo testes when pregnant mice were given drinking water contaminated with 10 µM of BPA in combination with radiation exposure [ 78 ]. The StAR protein was significantly reduced after 24 h of exposure to 70 mM of BPAF in the mouse Leydig cell tumor cell line (mLTC-1).…”