Germ Cell Development

Sex differences in germ cells are believed to be epigenetically regulated, as distinct differences in DNA methylation and histone modifications have been found in germ cells during sex determination. We are studying epigenetic regulation of germ cell development, including the process of epigenetic reprogramming of primordial germ cells (PGCs), by using olvasGFP medaka as a model organism.

Brain Sex Differences

In model organisms, mate selection and mating behaviors have been found to be affected by developmental exposure to environmental estrogenic or anti-androgenic chemicals, suggesting that current environmental levels of chemicals could be affecting the health and behavior of the exposed organisms. Our team is striving to understand epigenetic basis for brain sexual dimorphism and environmentally induced sex-specific behaviors.

Transgenerational Inheritance of Environmentally Induced Health Effects

The window of early embryonic development is susceptible to environmental chemical stressors. Exposures during gonadal sex determination may lead to reproductive defects in adulthood. These effects can be transgenerationally transmitted to subsequent generations via germ line (sperm and eggs).  Transgenerational effects appear in individuals not because of direct exposure but due to ancestral exposure and have been thought to be contributing to declining reproductive fitness and emergence of endangered species in natural populations. We are studying molecular alterations occurring during transgenerational inheritance of phenotypes to identify chemical and phenotype specific biomarkers associated with adverse reproductive outcomes using medaka fish (d-rR medaka, Oryzias latipes) as a model organism. We anticipate the biomarkers to be reliably predictive of history of exposure and associated transgenerational phenotypes.

Environmentally induced epigenetic memory

Gene-environment interactions can lead to emergence of phenotypes. Environmental stressors are able to induce epigenetic changes (chemical modifications on DNA structure) that are mitotically (and may even be meiotically) stable. Environmental stressor-induced chemical modifications, such as DNA methylation or histone modifications, may or may not survive epigenetic reprogramming events that occur during early cleavage stage of embryo or during re-specification of primordial germ cells (PGCs) at the time of sex determination. We hypothesize that the epigenetic modifications that survive reprogramming serve as epigenetic memories and that these memories are associated with adverse health outcomes.

Epigenetic effects of early developmental exposure to emerging environmental contaminants and AOP pathway

Growing number of studies reveal the fact that the aquatic environment is threatened by increasing rate of chemical contamination. As a result, aquatic fauna is impacted by ubiquitous presence of these chemicals in waterbodies. Our research suggests that developmentally established epigenetic changes can survive in the body throughout the lifetime of the exposed individual and are associated with adverse health effects later in life. We aim to develop an adverse outcome pathway (AOP) incorporating epigenetic effects and associated phenotypic traits using medaka fish as an animal model. In the near future, regulatory agencies will need scientific information to classify chemicals that are transgenerationally harmful to humans and ecosystem.