Environmentally Induced Epigenetic Transgenerational Inheritance of Reproductive Disease

Abstract

Reproductive disease and fertility issues have dramatically increased in the human population over the last several decades, suggesting environmental impacts. Epigenetics provides a mechanistic link by which an organism can respond to environmental factors. Interestingly, environmentally induced epigenetic alterations in the germ line can promote aberrant gene expression and disease generationally. Environmentally induced epigenetic transgenerational inheritance is defined as germ-line transmission of altered epigenetic information between generations in the absence of continued environmental exposures. This form of nongenetic inheritance has been shown to directly influence fertility and reproductive disease. This review describes the studies in a variety of species that impact reproductive disease and abnormalities. Observations suggest serious attention be paid to the possibility that ancestral exposures to environmental insults promotes transgenerational inheritance of reproductive disease susceptibility. Environmentally induced epigenetic transgenerational inheritance appears to be an important contributing factor to reproductive disease in many organisms, including humans.

Keywords: developmental biology; environment; epigenetics; genomics.

Fig. 1

Environmentally induced epigenetic transgenerational inheritance through male germ line. Exposure of the F0 generation gestating female, F1 generation fetus, and germ line within the F1 generation fetus that will generate the F2 generation. Therefore, the F3 generation is the first transgenerational generation not directly exposed. Figure modified from Skinner [61].

Fig. 2

Epigenetic programming of DNA methylation levels during development during gonadal sex determination, fertilization, and embryonic development. The green line is the male and the blue line the female developmental pattern. Figure modified from Jirtle and Skinner [27].

Fig. 3

Ancestral exposure specific epimutation biomarkers. Transgenerational F3 generation sperm differential DNA methylation regions (epimutations) with the total listed next to exposure in brackets and Venn diagram showing overlap between the exposure epimutations. Figure modified from Manikkam et al. [67].