Environmental exposures influence multigenerational epigenetic transmission

Abstract

Epigenetic modifications control gene expression and are essential for turning genes on and off to regulate and maintain differentiated cell types. Epigenetics are also modified by a multitude of environmental exposures, including diet and pollutants, allowing an individual's environment to influence gene expression and resultant phenotypes and clinical outcomes. These epigenetic modifications due to gene-environment interactions can also be transmitted across generations, raising the possibility that environmental influences that occurred in one generation may be transmitted beyond the second generation, exerting a long-lasting effect. In this review, we cover the known mechanisms of epigenetic modification acquisition, reprogramming and persistence, animal models and human studies used to understand multigenerational epigenetic transmission, and examples of environmentally induced epigenetic change and its transmission across generations. We highlight the importance of environmental health not only on the current population but also on future generations that will experience health outcomes transmitted through epigenetic inheritance.

Keywords: Environmental exposure; Epigenetic transmission; Reprogramming; Transgenerational inheritance.

Fig. 1

Epigenetic patterns observed across the life span. Epigenetic modifications change over time and increase with age as exposures accumulate. This epigenetic change occurs for both histone modifications (green line) and DNA methylation (orange line). Epigenetic regulation is retained from the parental sperm and egg and undergoes multiple rounds of reprogramming to assume a baseline epigenetic profile in the developing fetus. Some epigenetic marks persist through these reprogramming stages, allowing epigenetic transmission from earlier generation(s). Some epigenetic marks are acquired de novo due to the environment during pregnancy and during organ development in utero. After birth, epigenetic patterns continue to change most rapidly during growth and development in childhood and adolescence. Epigenetic modifications are continually acquired throughout life. The resultant epigenetic state in adulthood is then passed on to the next generation through the germ cells, and the cycle repeats. Figure was designed using biorender.com

Fig. 2

Preconception and prenatal exposures confer multigenerational inheritance of clinical outcomes through epigenetic modifications. Exposures, shown in the outer green circle, with known associations to altered epigenetic modifications include environmental pollutants from industrial plants, traffic fuel combustion, and fire smoke, diet and nutrition, exercise, stress from mental health, physical health and environmental health such as climate change, and behavioral and lifestyle factors such as smoking. These exposures induce changes in the epigenetic landscape of an individual, shown in the inner yellow circle, through DNA methylation, histone modifications, miRNA gene regulation, and 3D genome reorganization, that can be transmitted across one or more generations. Specific clinical outcomes, in the inner blue circle, are associated with these preconception and prenatal exposure-induced epigenetic modifications. Figure was designed using biorender.com