Epigenetic transgenerational actions of endocrine disruptors and male 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 F1 generation of decreased spermatogenic capacity (cell number and viability) and increased incidence of male infertility. These effects were transferred through the male germ line to nearly all males of all subsequent generations examined (that is, F1 to F4). 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.
Anway
Matthew D
MD
Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, WA 99164-4231, USA.
Cupp
Andrea S
AS
Uzumcu
Mehmet
M
Skinner
Michael K
MK
D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D003433:Crosses, Genetic; D019175:DNA Methylation; D004702:Endocrine Glands / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity; D044127:Epigenesis, Genetic / Q000187:drug effects; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D005298:Fertility / Q000187:drug effects* / Q000235:genetics; D005659:Fungicides, Industrial / Q000633:toxicity*; D007248:Infertility, Male / Q000139:chemically induced / Q000235:genetics; D040582:Inheritance Patterns; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D008731:Methoxychlor / Q000633:toxicity*; D010080:Oxazoles / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D013094:Spermatozoa / Q000187:drug effects
D000726:Androgen Antagonists; D004785:Environmental Pollutants; D004967:Estrogens; D005659:Fungicides, Industrial; D007306:Insecticides; D010080:Oxazoles; C025643:vinclozolin; D008731:Methoxychlor