Epigenetic impacts of endocrine disruptors in the brain.
The acquisition of reproductive competence is organized and activated by steroid hormones acting upon the hypothalamus during critical windows of development. This review describes the potential role of epigenetic processes, particularly DNA methylation, in the regulation of sexual differentiation of the hypothalamus by hormones. We examine disruption of these processes by endocrine-disrupting chemicals (EDCs) in an age-, sex-, and region-specific manner, focusing on how perinatal EDCs act through epigenetic mechanisms to reprogram DNA methylation and sex steroid hormone receptor expression throughout life. These receptors are necessary for brain sexual differentiation and their altered expression may underlie disrupted reproductive physiology and behavior. Finally, we review the literature on histone modifications and non-coding RNA involvement in brain sexual differentiation and their perturbation by EDCs. By putting these data into a sex and developmental context we conclude that perinatal EDC exposure alters the developmental trajectory of reproductive neuroendocrine systems in a sex-specific manner.
Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1065, New York, NY 10029, USA. Electronic address: walkerdeena@gmail.com.
Deena M
DM
Walker
Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA; Institute for Cellular and Molecular Biology, and The University of Texas at Austin, Austin, TX 78712, USA; Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712, USA.
Andrea C
AC
Gore
D000818:Animals; D052244:Endocrine Disruptors / Q000633:toxicity*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D057890:Epigenomics; D005260:Female; D006801:Humans; D008297:Male; D012313:RNA / Q000187:drug effects; D012098:Reproduction / Q000187:drug effects; D012727:Sex Characteristics
D052244:Endocrine Disruptors; D012313:RNA
DNA methylation; Endocrine-disrupting chemicals; Epigenetics; Histone modifications; Hypothalamus; Sex differences; Steroid hormone receptors
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