Replacement Bisphenols Adversely Affect Mouse Gametogenesis with Consequences for Subsequent Generations

• Published in: Current biology 2018-09, Vol.28 (18), p.2948-2954.e3
• Main Authors: Horan, Tegan S., Pulcastro, Hannah, Lawson, Crystal, Gerona, Roy, Martin, Spencer, Gieske, Mary C., Sartain, Caroline V., Hunt, Patricia A.
• Format: Article
• Language: English
• Subjects: Animals; bisphenols; BPA; BPS; EDCs; Environmental Pollutants - adverse effects; Female; Gametogenesis - drug effects; Male; meiosis; Meiosis - drug effects; Mice; Mice, Inbred C57BL; oogenesis; Phenols - adverse effects; spermatogenesis; Sulfones - adverse effects; transgenerational
• ISSN: 0960-9822; 1879-0445; 1879-0445
• DOI: 10.1016/j.cub.2018.06.070

20 years ago, accidental bisphenol A (BPA) exposure caused a sudden increase in chromosomally abnormal eggs from our control mice [1]. Subsequent rodent studies demonstrated developmental effects of exposure with repercussions on adult health and fertility (e.g., [2–9]; reviewed in [10–17]). Studies in monkeys, humans, fish, and worms suggest BPA effects extend across species (e.g., [18–30]; reviewed in [31–33]). Widespread use has resulted in ubiquitous environmental contamination and human BPA exposure. Consumer concern resulted in “BPA-free” products produced using structurally similar bisphenols that are now detectable environmental and human contaminants (e.g., [34–41]). We report here studies initiated by meiotic changes mirroring our previous BPA experience and implicating exposure to BPS (a common BPA replacement) from damaged polysulfone cages. Like with BPA [1, 2, 5], our data show that exposure to common replacement bisphenols induces germline effects in both sexes that may affect multiple generations. These findings add to growing evidence of the biological risks posed by this class of chemicals. Rapid production of structural variants of BPA and other EDCs circumvents efforts to eliminate dangerous chemicals, exacerbates the regulatory burden of safety assessment, and increases environmental contamination. Our experience suggests that these environmental contaminants pose a risk not only to reproductive health but also to the integrity of the research environment. EDCs, like endogenous hormones, can affect diverse processes. The sensitivity of the germline allows us to detect effects that, although not immediately apparent in other systems, may induce variability that undermines experimental reproducibility and impedes scientific advancement. •Replacement bisphenols are structural BPA variants with similar biological effects•Common bisphenols are germline toxicants that induce meiotic effects in both sexes•Genotoxic bisphenol exposure effects may persist for several generations in males•Environmental contaminants can undermine science by affecting data and conclusions Horan et al. report changes in meiotic data in mice coinciding with physical damage to polysulfone cages. LCMS analyses implicate replacement bisphenols. Subsequent controlled experiments demonstrate that, like BPA, common replacement bisphenols induce meiotic effects in both sexes that, in males, may persist for several generations.