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Publication Detail

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

Authors: Martini, Mariangela; Corces, Victor G; Rissman, Emilie F

Published In Horm Behav, (2020 03)

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.

PubMed ID: 31927019 Exiting the NIEHS site

MeSH Terms: Animals; Behavior/drug effects*; Behavioral Research/methods; Behavioral Research/trends; Cohort Effect; DNA Methylation/drug effects; Endocrine Disruptors/pharmacology*; Environmental Exposure/analysis; Environmental Exposure/statistics & numerical data; Epigenesis, Genetic/drug effects*; Epigenesis, Genetic/physiology*; Female; Humans; Male; Nervous System/drug effects; Nervous System/embryology; Nervous System/growth & development; Neuroendocrinology/methods; Neuroendocrinology/trends; Pregnancy; Prenatal Exposure Delayed Effects/chemically induced; Prenatal Exposure Delayed Effects/genetics*; Prenatal Exposure Delayed Effects/physiopathology; Reproduction/drug effects; Sex Differentiation/drug effects

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