title: Multigenerational and transgenerational effects of endocrine disrupting chemicals: A role for altered epigenetic regulation?
abstract: Increasing evidence has highlighted the critical role of early life environment in shaping the future health outcomes of an individual. Moreover, recent studies have revealed that early life perturbations can affect the health of subsequent generations. Hypothesized mechanisms of multi- and transgenerational inheritance of abnormal developmental phenotypes include epigenetic misregulation in germ cells. In this review, we will focus on the available data demonstrating the ability of endocrine disrupting chemicals (EDCs), including bisphenol A (BPA), phthalates, and parabens, to alter epigenetic marks in rodents and humans. These epigenetic marks include DNA methylation, histone post-translational modifications, and non-coding RNAs. We also review the current evidence for multi- and transgenerational inheritance of abnormal developmental changes in the offspring following EDC exposure. Based on published results, we conclude that EDC exposure can alter the mouse and human epigenome, with variable tissue susceptibilities. Although increasing data suggest that exposure to EDCs is linked to transgenerational inheritance of reproductive, metabolic, or neurological phenotypes, more studies are needed to validate these observations and to elucidate further whether these developmental changes are directly associated with the relevant epigenetic alterations.
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, 9-123 Smilow Center for Translational Research, Philadelphia, PA 19104, United States; Center of Excellence in Environmental Toxicology, University of Pennsylvania Perelman School of Medicine, 1316 Biomedical Research Building II/III, Philadelphia, PA 19104, United States.
authors.forename: Frances
authors.initials: F
authors.lastname: Xin
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, 9-123 Smilow Center for Translational Research, Philadelphia, PA 19104, United States; Center of Excellence in Environmental Toxicology, University of Pennsylvania Perelman School of Medicine, 1316 Biomedical Research Building II/III, Philadelphia, PA 19104, United States.
authors.forename: Martha
authors.initials: M
authors.lastname: Susiarjo
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, 9-123 Smilow Center for Translational Research, Philadelphia, PA 19104, United States; Center of Excellence in Environmental Toxicology, University of Pennsylvania Perelman School of Medicine, 1316 Biomedical Research Building II/III, Philadelphia, PA 19104, United States. Electronic address: bartolom@mail.med.upenn.edu.
authors.forename: Marisa S
authors.initials: MS
authors.lastname: Bartolomei
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000494:pharmacology*; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D052244:Endocrine Disruptors / Q000009:adverse effects / Q000494:pharmacology*; D044127:Epigenesis, Genetic / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D040582:Inheritance Patterns / Q000187:drug effects*; D051379:Mice; D010226:Parabens / Q000009:adverse effects / Q000494:pharmacology*; D010636:Phenols / Q000009:adverse effects / Q000494:pharmacology*; D010641:Phenotype; D010795:Phthalic Acids / Q000009:adverse effects / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000235:genetics; D022661:RNA, Untranslated / Q000187:drug effects / Q000235:genetics; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D010226:Parabens; D010636:Phenols; D010795:Phthalic Acids; D022661:RNA, Untranslated; C032279:phthalic acid; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; Endocrine disrupting chemicals; Epigenetics; Parabens; Phthalates; Transgenerational inheritance