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      Developmental origins of epigenetic transgenerational inheritance

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          Abstract

          Environmental factors can induce epigenetic alterations in the germ cells that can potentially be transmitted transgenerationally. This non-genetic form of inheritance is termed epigenetic transgenerational inheritance and has been shown in a variety of species including plants, flies, worms, fish, rodents, pigs, and humans. This phenomenon operates during specific critical windows of exposure, linked to the developmental biology of the germ cells (sperm and eggs). Therefore, concepts of the developmental origins of transgenerational inheritance of phenotypic variation and subsequent disease risk need to include epigenetic processes affecting the developmental biology of the germ cell. These developmental impacts on epigenetic transgenerational inheritance, in contrast to multigenerational exposures, are the focus of this Perspective.

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          Plastics Derived Endocrine Disruptors (BPA, DEHP and DBP) Induce Epigenetic Transgenerational Inheritance of Obesity, Reproductive Disease and Sperm Epimutations

          Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1–F3) following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the “plastics” or “lower dose plastics” mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries) were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR) in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures.
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            Developmental plasticity and evolution

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              Developmental plasticity and the evolution of parental effects.

              One of the outstanding challenges for evolutionary biologists is to understand how developmental plasticity can influence the evolutionary process. Developmental plasticity frequently involves parental effects, which might enable adaptive and context-dependent transgenerational transmission of phenotypic strategies. However, parent-offspring conflict will frequently result in parental effects that are suboptimal for parents, offspring or both. The fitness consequences of parental effects at evolutionary equilibrium will depend on how conflicts can be resolved by modifications of developmental processes, suggesting that proximate studies of development can inform ultimate questions. Furthermore, recent studies of plants and animals show how studies of parental effects in an ecological context provide important insights into the origin and evolution of adaptation under variable environmental conditions.
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                Author and article information

                Journal
                101675941
                44874
                Environ Epigenet
                Environ Epigenet
                Environmental epigenetics
                2058-5888
                15 March 2016
                6 March 2016
                2016
                05 July 2016
                : 2
                : 1
                : dvw002
                Affiliations
                [1 ]Institute of Developmental Sciences, University of Southampton and NIHR Nutrition Biomedical Research Centre, Southampton General Hospital, Southampton, SO 16 6YD, UK
                [2 ]School of Biological Sciences, Center for Reproductive Biology, Washington State University, Pullman, WA 99164-4236, USA
                Author notes
                [* ]Correspondence address. School of Biological Sciences, Center for Reproductive Biology, Washington State University, Pullman, WA 99164-4236. Tel: 509-335-1524; Fax: 509-335-2176; skinner@ 123456wsu.edu
                Article
                NIHMS768199
                10.1093/eep/dvw002
                4933018
                27390622
                d0f03872-9c39-45df-b5a0-8acb04c5cc30

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                transgenerational,epigenetic,disease,generational,critical windows

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