Sexually Dimorphic Effects of Early-Life Exposures to Endocrine Disruptors: Sex-Specific Epigenetic Reprogramming as a Potential Mechanism
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Purpose of Review
The genetic material of every organism exists within the context of regulatory networks that govern gene expression—collectively called the epigenome. Animal models and human birth cohort studies have revealed key developmental periods that are important for epigenetic programming and vulnerable to environmental insults. Thus, epigenetics represent a potential mechanism through which sexually dimorphic effects of early-life exposures such as endocrine-disrupting chemicals (EDCs) manifest.
Several animal studies, and to a lesser extent human studies, have evaluated life-course sexually dimorphic health effects following developmental toxicant exposures; many fewer studies, however, have evaluated epigenetics as a mechanism mediating developmental exposures and later outcomes.
To evaluate epigenetic reprogramming as a mechanistic link of sexually dimorphic early-life EDCs exposures, the following criteria should be met: (1) well-characterized exposure paradigm that includes relevant windows for developmental epigenetic reprogramming; (2) evaluation of sex-specific exposure-related epigenetic change; and (3) observation of a sexually dimorphic phenotype in either childhood, adolescence, or adulthood.
KeywordsLead (Pb) Bisphenol A (BPA) Epigenetics Sexually dimorphic effects Developmental origins of health and disease (DOHaD)
Kari Neier was supported by training grant T32 079342 from the National Institute of Child Health and Human Development (NICHD) while preparing this manuscript, and Luke Montrose was supported by T32 ES007062 from the National Institute of Environmental Health Sciences (NIEHS). This work was also supported by the University of Michigan (UM) NIEHS/EPA Children’s Environmental Health and Disease Prevention Center P01 ES022844/RD83543601, the Michigan Lifestage Environmental Exposures and Disease (M-LEEaD) NIEHS Core Center (P30 ES017885),
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Conflict of Interest
The authors declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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