Environmentally-Induced Epigenetic Transgenerational Inheritance of Altered Sertoli cell Transcriptome and Epigenome

Epigenetic transgenerational inheritance is induced by the action of environmental
toxicants on pregnant mothers and epigenetic alterations of the germ line in their developing
embryos. This early developmental exposure generates phenotypic variation in the adult
individuals and in the unexposed individuals in subsequent generations. The germ line plays a
fundamental role in this transgenerational process because it transmits acquired epigenetic
modifications between generations. Epigenetic modifications in the germ line take place during
developmentally sensitive periods undergoing major reprogramming of DNA methylation. It is
not known, however, how these germ line epigenomic transgenerational modifications affect
somatic epigenomic states or tissue specific phenotypes. The present study investigates
somatic epigenetic changes produced in Sertoli cells (fundamental to spermatogenesis) in F3
animals from a lineage of individual originated from an early developmental exposure to
vinclozolin. Vinclozolin is an environmental toxicant known to alter germ line development,
impairing spermatogenesis not only in the adults exposed but also in their non-exposed
descendants. Vinclozolin-induced transgenerational alterations in DNA methylation have been
previously identified in the rat sperm DNA. These transgenerational changes in DNA
methylation appear to influence gene expression of adult somatic cells in different tissues. The
present study reports for the first time epigenetic and gene expression transgenerational
changes in Sertoli cells three generations after a germ line developmental exposure to the
endocrine disruptor vinclozolin. Therefore, an early developmental exposure to vinclozolin that
interferes with the germ line epigenome programming can induce a germ line mediated
transgenerational inheritance of a somatic methylome and transcriptome in future generations.
Correlations between epigenetic and gene expression were investigated. Further molecular
biology experiments are needed to determine specific mechanisms involved in each of these
correlations. The present study has implications on male fertility, by inquiring on the
mechanism behind specific types of fertility impairments that could be consequence of
ancestor exposure.