Transgenerational epigenetic and transcriptomic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure in rat [array]

In rats, direct exposure to TCDD causes myriad toxicities. Exposed rats experience hepatotoxicity, wasting syndrome and immune suppression, amongst others. “Inherited exposure”, as occurs in the F3 generation of directly exposed F0 animals, has also been shown to cause toxicity: both male and female F3 rats demonstrate an increased incidence of adult onset disease, females also display reproductive abnormalities and increased incidence of ovarian diseases while males show increased incidence of kidney disease and an altered sperm epigenome. Here, we explore the hepatic transcriptomic profile of male and female F3 Sprague-Dawley rats bred through the paternal germ line from F0 dams exposed to a single dose of TCDD (0, 30, 100, 300 or 1000 ng/kg body weight) by oral gavage. We hypothesize that RNA transcripts with altered abundance in livers of unexposed F3 progeny of treated F0 Sprague-Dawley rats may result from epigenetic modifications to the genome. Female F3 rats demonstrated more TCDD-mediated hepatic transcriptomic changes than males, with differences primarily in the lowest dose group. On gestational day 11, groups of pregnant female Sprague-Dawley rats (n=6-8) were treated with a single dose of TCDD (0, 30, 100, 300 and 1000 ng/kg bodyweight) dissolved in corn oil by oral gavage. Adult male F1 progeny were mated with untreated female rats to achieve F2 generations. The above procedure was repeated to further achieve F3 generations. At the end of the examination period, rats were euthanized by carbon dioxide exposure and subjected to tissue sampling. Hepatic tissue was shipped on dry ice to the analytical laboratory for processing.