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An in vitro approach reveals molecular mechanisms underlying endocrine disruptor-induced epimutagenesis.
Lehle, Jake D; Lin, Yu-Huey; Gomez, Amanda; Chavez, Laura; McCarrey, John R.
Afiliação
  • Lehle JD; Department of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio, San Antonio, United States.
  • Lin YH; Department of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio, San Antonio, United States.
  • Gomez A; Department of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio, San Antonio, United States.
  • Chavez L; Department of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio, San Antonio, United States.
  • McCarrey JR; Department of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio, San Antonio, United States.
Elife ; 132024 Oct 03.
Article em En | MEDLINE | ID: mdl-39361026
ABSTRACT
Endocrine disrupting chemicals (EDCs) such as bisphenol S (BPS) are xenobiotic compounds that can disrupt endocrine signaling due to steric similarities to endogenous hormones. EDCs have been shown to induce disruptions in normal epigenetic programming (epimutations) and differentially expressed genes (DEGs) that predispose disease states. Most interestingly, the prevalence of epimutations following exposure to many EDCs persists over multiple generations. Many studies have described direct and prolonged effects of EDC exposure in animal models, but many questions remain about molecular mechanisms by which EDC-induced epimutations are introduced or subsequently propagated, whether there are cell type-specific susceptibilities to the same EDC, and whether this correlates with differential expression of relevant hormone receptors. We exposed cultured pluripotent (iPS), somatic (Sertoli and granulosa), and primordial germ cell-like (PGCLC) cells to BPS and found that differential incidences of BPS-induced epimutations and DEGs correlated with differential expression of relevant hormone receptors inducing epimutations near relevant hormone response elements in somatic and pluripotent, but not germ cell types. Most interestingly, we found that when iPS cells were exposed to BPS and then induced to differentiate into PGCLCs, the prevalence of epimutations and DEGs was largely retained, however, >90% of the specific epimutations and DEGs were replaced by novel epimutations and DEGs. These results suggest a unique mechanism by which an EDC-induced epimutated state may be propagated transgenerationally.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenóis / Disruptores Endócrinos Limite: Animals Idioma: En Revista: Elife Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenóis / Disruptores Endócrinos Limite: Animals Idioma: En Revista: Elife Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido