Abstract
Concerns about the safety of Bisphenol A, a chemical found in plastics, receipts, food packaging and more, have led to its replacement with substitutes now found in a multitude of consumer products. However, several popular BPA-free alternatives, such as Bisphenol S, share a high degree of structural similarity with BPA, suggesting that these substitutes may disrupt similar developmental and reproductive pathways. We compared the effects of BPA and BPS on germline and reproductive functions using the genetic model system Caenorhabditis elegans. We found that, similarly to BPA, BPS caused severe reproductive defects including germline apoptosis and embryonic lethality. However, meiotic recombination, targeted gene expression, whole transcriptome and ontology analyses as well as ToxCast data mining all indicate that these effects are partly achieved via mechanisms distinct from BPAs. These findings therefore raise new concerns about the safety of BPA alternatives and the risk associated with human exposure to mixtures.
Highlights
Delineating the effects of environmental chemicals on biological processes is a fundamental challenge with direct relevance to public health
The intricacy of dealing with chemical alternatives is salient in the case of Bisphenol A which was largely driven out of commercial products in North America by consumer and NGO pressure
We report that Bisphenol S (BPS) exposure, to Bisphenol A (BPA), significantly reduces the nematode’s fertility and impairs proper homologous chromosome synapsis during meiotic differentiation, which in turn induces germline checkpoint activation and germline apoptosis
Summary
Delineating the effects of environmental chemicals on biological processes is a fundamental challenge with direct relevance to public health. Rodent exposure to physiologically relevant doses of BPA (approximately 400 ng/ day) has revealed two windows of germ cell sensitivity [9]. On the other hand, impacts the early stages of germ cell meiotic differentiation in rodents as well as in rhesus monkeys [9, 11]. The associated process of meiotic recombination is altered as shown by an increase in homologous crossover frequency [9]. The alteration of these two fundamental meiotic processes correlates with an increased incidence of chromosome end-to-end associations as well as oocyte and embryonic aneuploidy [9, 11]
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