Mini-review: Epigenetic mechanisms that promote transgenerational actions of endocrine disrupting chemicals: Applications to behavioral neuroendocrinology

• Type of Material: Article
• Authors: Mariangela Martini, North Carolina State University; Victor Corces, Emory University; Emilie F Rissman, North Carolina State University
• Language: English
• Date: 2020-03-01
• Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020 Published by Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.yhbeh.2020.104677
• Title of Journal or Parent Work: HORMONES AND BEHAVIOR
• Volume: 119
• Start Page: 104677
• End Page: 104677
• Keywords: Bisphenol; ESTROGEN-RECEPTOR FUNCTION; Endocrinology & Metabolism; Phthalates; Behavioral Sciences; Transcription factors; Methylation; DNA METHYLATION; Science & Technology; CTCF; Vinclozolin; DEVELOPMENTAL ORIGINS; Androgen; SEX-DIFFERENCES; METABOLIZING ENZYMES; GENE-EXPRESSION; Estrogen; PCB; Transgenerational; Endocrine disrupting chemicals; BISPHENOL-A EXPOSURE; IN-UTERO; Life Sciences & Biomedicine; NEONATAL EXPOSURE; Chromatin; TESTOSTERONE PROPIONATE

Abstract

It is our hope this mini-review will stimulate discussion and new research. Here we briefly examine the literature on transgenerational actions of endocrine disrupting chemicals (EDCs) on brain and behavior and their underlying epigenetic mechanisms including: DNA methylation, histone modifications, and non-coding RNAs. We stress that epigenetic modifications need to be examined in a synergistic manner, as they act together in situ on chromatin to change transcription. Next we highlight recent work from one of our laboratories (VGC). The data provide new evidence that the sperm genome is poised for transcription. In developing sperm, gene enhancers and promoters are accessible for transcription and these activating motifs are also found in preimplantation embryos. Thus, DNA modifications associated with transcription factors during fertilization, in primordial germ cells (PGCs), and/or during germ cell maturation may be passed to offspring. We discuss the implications of this model to EDC exposures and speculate on whether natural variation in hormone levels during fertilization and PGC migration may impart transgenerational effects on brain and behavior. Lastly we discuss how this mechanism could apply to neural sexual differentiation.