Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset disease.
The fetal basis of adult disease is poorly understood on a molecular level and cannot be solely attributed to genetic mutations or a single etiology. Embryonic exposure to environmental compounds has been shown to promote various disease states or lesions in the first generation (F1). The current study used the endocrine disruptor vinclozolin (antiandrogenic compound) in a transient embryonic exposure at the time of gonadal sex determination in rats. Adult animals from the F1 generation and all subsequent generations examined (F1-F4) developed a number of disease states or tissue abnormalities including prostate disease, kidney disease, immune system abnormalities, testis abnormalities, and tumor development (e.g. breast). In addition, a number of blood abnormalities developed including hypercholesterolemia. The incidence or prevalence of these transgenerational disease states was high and consistent across all generations (F1-F4) and, based on data from a previous study, appears to be due in part to epigenetic alterations in the male germ line. The observations demonstrate that an environmental compound, endocrine disruptor, can induce transgenerational disease states or abnormalities, and this suggests a potential epigenetic etiology and molecular basis of adult onset disease.
Anway
Matthew D
MD
Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, Washington 99164-4231, USA.
Leathers
Charles
C
Skinner
Michael K
MK
D000818:Animals; D003433:Crosses, Genetic; D052244:Endocrine Disruptors / Q000009:adverse effects*; D044127:Epigenesis, Genetic; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D030342:Genetic Diseases, Inborn / Q000139:chemically induced*; D006801:Humans; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D009369:Neoplasms / Q000139:chemically induced; D010080:Oxazoles / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley
D052244:Endocrine Disruptors; D010080:Oxazoles; C025643:vinclozolin