BPA interferes with StAR-mediated mitochondrial cholesterol transport to induce germline dysfunctions.
Molecular Toxicology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Institute for Society and Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
California State University Northridge, Northridge, CA 91330, USA.
Department of Environmental Health Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Molecular Toxicology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Society and Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: [email protected]
- Published Article
Reproductive toxicology (Elmsford, N.Y.)
- Publication Date
Dec 01, 2019
Bisphenol A is an endocrine disruptor associated with hormone synthesis and reproduction alterations. However, the initiating events underpinning these dysfunctions are still unclear. Here, we address the hypothesis that BPA interferes with the highly evolutionary conserved process of mitochondrial cholesterol transport, a crucial step in steroid hormone biosynthesis, by using the model organism C. elegans. We observed that embryonic lethality and germline apoptosis, hallmarks of BPA's reproductive toxicity in C. elegans, are fully rescued by low exogenous cholesterol supplementation. We also observed that increasing BPA concentrations proportionally reduced mitochondrial cholesterol levels. Mutants for strl-1 (ortholog of StAR), but not C41G7.9 (ortholog of TSPO), show reproductive defects similar to BPA's while BPA exposure in a strl-1 background did not worsen these effects. Finally, cholesterol supplementation rescued these defects for all strl-1 genotype/BPA combinations assessed. Together, these results uncover a novel mechanism underlying BPA's germline toxicity through the alteration of cholesterol transport. Copyright © 2019 Elsevier Inc. All rights reserved.
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This record was last updated on 12/31/2019 and may not reflect the most current and accurate biomedical/scientific data available from NLM.
The corresponding record at NLM can be accessed at https://www.ncbi.nlm.nih.gov/pubmed/31445225