ToxSci Advance Access originally published online on March 7, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Toxicological Sciences 72, 242-252 (2003)
Copyright © 2003 by the Society of Toxicology
ENVIRONMENTAL TOXICOLOGY |
Gestational Exposure to Persistent Organic Pollutants: Maternal Liver Residues, Pregnancy Outcome, and Effects on Hepatic Gene Expression Profiles in the Dam and Fetus
,
* Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Montréal, Québec H3G 1Y6, Canada;
Toxicology Research Division, Health Products and Food Branch, Food Directorate, Health Canada, Tunney’s Pasture, Ottawa, Ontario K1A 0L2, Canada;
Departments of Cellular and Molecular Medicine, Obstetrics and Gynecology, University of Ottawa, Ottawa, Ontario, Canada; and
Departments of Pediatrics and Human Genetics, and
¶ Department of Obstetrics and Gynecology, McGill University, Montréal, Québec H3G 1Y6, Canada
Dietary exposure of Inuit people to a mixture of pesticides and polychlorinated biphenyls, or persistent organic pollutants (POPs), during pregnancy is a public health concern. We examined the consequences of administering the mixture of 28 POPs found in the Inuit diet (at doses representing 10–1000 times dietary levels) by gavage to pregnant Sprague-Dawley rats either during gestation days 0–19 or 8–19. The levels of individual components of the POPs mixture in the maternal liver were measured by high-resolution mass spectrometry. On gestation day 20, dams were sacrificed and pregnancy outcome determined. RNA isolated from maternal and fetal livers was 32P-labeled for gene expression profiling. The concentrations of individual POPs were increased in maternal livers of dams gavaged with the 1000x POPs mixture by 10- to 500-fold. While exposure to POPs had no significant effects on pregnancy outcome, dramatic changes were observed in the gene expression profiles of both the maternal and fetal livers. The gene expression profiles of maternal and fetal female and male liver were distinct with respect to the numbers of transcripts detected, the genes expressed exclusively in control or POPs-exposed livers, and those for which expression was up- or downregulated. While different genes were affected in each group, the overall consequence of POPs exposure on hepatic gene expression profiles was to decrease both the numbers of genes expressed and the relative intensity of expression. Thus, in utero exposure to POPs alters hepatic gene expression in the dam and the fetus; these changes may have functional implications.
Key Words: persistent organic pollutants; microarray; liver; rat; fetus; pregnancy; gene expression; Inuit diet.