Environmental Epigenetics and Effects on Male Fertility

Environmental exposures to factors such as toxicants or nutrition can have impacts on testis biology and male fertility. The ability of these factors to influence epigenetic mechanisms in early life exposures or from ancestral exposures will be reviewed. A growing number of examples suggest environmental epigenetics will be a critical factor to consider in male reproduction

Transgenerational epigenetic actions of environmental compounds

Endocrine disrupting chemicals are known for their capacity to alter development and reproduction in mammals. One of the periods most sensitive to endocrine disruptor exposure is embryonic gonadal sex determination, when the germ line is undergoing epigenetic programming and DNA re-methylation. Epigenetic changes derived from exposure to endocrine disruptors have been described in several tissues and organisms. Endocrine disruptor induced epigenetic changes may have a wide range of phenotypic consequences, leading to disease conditions such as cancers, reproductive defects and obesity. Interestingly, the incidence of some diseases resulting from exposure to endocrine disruptors can be transgenerationally transmitted. In particular, exposure to the endocrine disruptor vinclozolin during early development is capable of inducing adult onset disease states that can be perpetuated across multiple generations. Environmental compounds such as endocrine disruptors can produce changes in the genome without altering DNA sequence. These changes are epigenetic in basis and can produce phenotypes that perpetuate transgenerationally. The suggestion that environmental factors can reprogram early development to induce epigenetic transgenerational phenotypes is a new paradigm in biology that will open new avenues for studies in disease etiology, reproduction and evolutionary biology

Epigenetic and phenotypic changes result from a continuous pre and post natal dietary exposure to phytoestrogens in an experimental population of mice

Background: Developmental effects of exposure to endocrine disruptors can influence adult characters in mammals, but could also have evolutionary consequences. The aim of this study was to simulate an environmental exposure of an experimental population of mice to high amounts of nutritional phytoestrogens and to evaluate parameters of relevance for evolutionary change in the offspring. The effect of a continuous pre- and post-natal exposure to high levels of dietary isoflavones was evaluated on sexual maturity, morphometric parameters and DNA methylation status in mice. Adult mice male/female couples were fed ad libitum either with control diet (standard laboratory chow) or ISF diet (control diet plus a soy isoflavone extract at 2% (w/w) that contained the phytoestrogens genistein and daidzein). In the offspring we measured: i) the onset of vaginal opening (sexual maturation) in females, ii) weight and size in all pups at 7, 14, 21 and 42 days post-natal (dpn) and iii) DNA methylation patterns in skeletal α-actin (Acta1), estrogen receptor- α and c-fos in adults (42 dpn). Results: Vaginal opening was advanced in female pups in the ISF group, from 31.6 ± 0.75 dpn to 25.7 ± 0.48. No differences in size or weight at ages 7, 14 or 21 dpn were detected between experimental groups. Nevertheless, at age 42 dpn reduced size and weight were observed in ISF pups, in addition to suppression of normal gender differences in weight seen in the control group (males heavier that females). Also, natural differences seen in DNA methylation at Acta1 promoter in the offspring originated in the control group were suppressed in the ISF group. Acta1 is known to be developmentally regulated and related to morphomotric features. Conclusion: This study demonstrates in mammals that individuals from a population subjected to a high consumption of isoflavones can show alterations in characters that may be of importance from an evolutionary perspective, such as epigenetic and morphometric characters or sexual maturation, a life history character.We greatly appreciate the linguistic revision of the manuscript by Renée Hill and critical review of the manuscript by Dr. Anders Lindroth. We are very thankful for funding by FONDECYT projects 1010647 to PS and 1030309 to LV, CONICYT fellowship for graduate studies and MECESUP grant for overseas training to CG, and NH&MRC project grant funding to SJC

Practical application of a Bayesian network approach to poultry epigenetics and stress

This work was supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 812777. We also greatly appreciate funding from the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS) grants #2018-01074 and #2017-00946 to CG-B. FP appreciates funding from São Paulo Research Foundation (FAPESP, Brazil) projects #2016/20440-3 and #2018/13600-0.Background: Relationships among genetic or epigenetic features can be explored by learning probabilistic networks and unravelling the dependencies among a set of given genetic/epigenetic features. Bayesian networks (BNs) consist of nodes that represent the variables and arcs that represent the probabilistic relationships between the variables. However, practical guidance on how to make choices among the wide array of possibilities in Bayesian network analysis is limited. Our study aimed to apply a BN approach, while clearly laying out our analysis choices as an example for future researchers, in order to provide further insights into the relationships among epigenetic features and a stressful condition in chickens (Gallus gallus). Results: Chickens raised under control conditions (n = 22) and chickens exposed to a social isolation protocol (n = 24) were used to identify differentially methylated regions (DMRs). A total of 60 DMRs were selected by a threshold, after bioinformatic pre-processing and analysis. The treatment was included as a binary variable (control = 0; stress = 1). Thereafter, a BN approach was applied: initially, a pre-filtering test was used for identifying pairs of features that must not be included in the process of learning the structure of the network; then, the average probability values for each arc of being part of the network were calculated; and finally, the arcs that were part of the consensus network were selected. The structure of the BN consisted of 47 out of 61 features (60 DMRs and the stressful condition), displaying 43 functional relationships. The stress condition was connected to two DMRs, one of them playing a role in tight and adhesive intracellular junctions in organs such as ovary, intestine, and brain. Conclusions: We clearly explain our steps in making each analysis choice, from discrete BN models to final generation of a consensus network from multiple model averaging searches. The epigenetic BN unravelled functional relationships among the DMRs, as well as epigenetic features in close association with the stressful condition the chickens were exposed to. The DMRs interacting with the stress condition could be further explored in future studies as possible biomarkers of stress in poultry species.Publisher PDFPeer reviewe

High type II error and interpretation inconsistencies when attempting to refute transgenerational epigenetic inheritance

A recently published article in Genome Biology attempts to refute important aspects of the phenomenon of transgenerational epigenetic inheritance (TEI). An alternative explanation of the data is offered here, showing that TEI is indeed not contradicted.Please see related Correspondence article: www.dx.doi.org/10.1186/s13059-016-0981-5 and related Research article: http://genomebiology.biomedcentral.com/articles/10.1186/s13059-015-0619-z.Funding agencies:CGB greatly appreciates support by the ERC grant GeneWell</p

Transgenerational epigenetic inheritance in birds

While it has been shown that epigenetics accounts for a portion of the variability of complex traits linked to interactions with the environment, the real contribution of epigenetics to phenotypic variation remains to be assessed. In recent years, a growing number of studies have revealed that epigenetic modifications can be transmitted across generations in several animal species. Numerous studies have demonstrated inter- or multi-generational effects of changing environment in birds, but very few studies have been published showing epigenetic transgenerational inheritance in these species. In this review, we mention work conducted in parent-to-offspring transmission analyses in bird species, with a focus on the impact of early stressors on behaviour. We then present recent advances in transgenerational epigenetics in birds, which involve germline linked non-Mendelian inheritance, underline the advantages and drawbacks of working on birds in this field and comment on future directions of transgenerational studies in bird species

Globalization, climate change, and transgenerational epigenetic inheritance: will our descendants be at risk?

Transgenerational epigenetic inheritance has gained increased attention due to the possibility that exposure to environmental contaminants induce diseases that propagate  across generations through epigenomic alterations in gametes. In laboratory animals,exposure to environmental toxicants such as fungicides, pesticides, or plastic compounds has been shown to produce abnormal reproductive or metabolic phenotypes that are transgenerationally transmitted. Human exposures to environmental toxicants have increased due to industrialization and globalization, as well as the incidence of diseases shown to be transgenerationally transmitted in animal models. This new knowledge poses an urgent call to study transgenerational  consequences of current human exposures to environmental toxicants