Epigenetic transgenerational actions of endocrine disruptors and mate fertility

Transgenerational effects of environmental toxins require either a chromosomal or epigenetic alteration in the germ line. Transient exposure of a gestating female rat during the period of gonadal sex determination to the endocrine disruptors vinclozolin (an antiandrogenic compound) or methoxychlor (an estrogenic compound) induced an adult phenotype in the F-1 generation of decreased spermatogenic capacity (cell number and viability) and increased incidence of mate infertility. These effects were transferred through the mate germ line to nearly all mates of ail subsequent generations examined (that is F-1 to F-4). The effects on reproduction correlate with altered DNA methylation patterns in the germ line. The ability of an environmental factor (for example, endocrine disruptor) to reprogram the germ line and to promote a transgenerational disease state has significant implications for evolutionary biology and disease etiology.