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Exposure of pregnant rats to diverse chemicals during pregnancy causes elevated blood pressure in offspring
Citation:
ROGERS, J. M., R. G. ELLIS-HUTCHINGS, J. NORWOOD, AND C. Lau. Exposure of pregnant rats to diverse chemicals during pregnancy causes elevated blood pressure in offspring. Presented at International Society for Developmental Origins of Health and Disease(DOHaD), Santiago, CHILE, November 19 - 22, 2009.
Impact/Purpose:
Present data on the effects of developmental exposure to chemicals on adult health
Description:
Objective: Global undernutrition, low protein diet or dexamethasone treatment during pregnancy has been demonstrated in animal models to result in adverse health effects including hypertension and insulln resistance in adult offspring. Most protocols that produce these effects cause in utero growth retardation (IUGR). IUGR is also common in prenatal developmental toxicity studies. Here we examine long term effects of in utero chemical exposure. Methods: Pregnant rats were exposed to chemicals at dosages chosen to result in small decrements in birth weight. Chemicals studied included dexamethasone (positive contro!), perfluorooctane sulfonate (PFOS), atrazine, arsenic, perfluorononanoic acid (PFNA), nicotine, and toluene. Following parturition, offspring were cross-fostered to untreated dams and their survival and growth monitored. Offspring blood pressure (tail-cuff) and insulin response (ELISA) to oral glucose challenge were measured at several ages. Some offspring were killed on postnatal day I for measurement of kidney glucocorticoid receptor mRNA by qRT-PCR and some were killed at day 22 to collect kidneys for nephron counts by confocal microscopy. At the end of the study, animals were killed and serum chemistries assessed. Results: Chemical exposure during pregnancy resulted in birth weights significantly lower than controls for dexamethasone, atrazine, and PFNA, and nominally lower for PFOS and nicotine. Offspring weights were similar to control by weaning except for dexamethasone. At 7-10 weeks of age, systolic blood pressure was higher than controls in male offspring of dams exposed to dexamethasone, atrazine, PFOS, PFNA, and toluene and significantly higher in females for PFNA and arsenic. Females in general were affected later than males; PFOS, dexamethasone and atrazine female had elevated blood pressures by 37 weeks. By 52-65 weeks of age, both males a females showed elevated blood pressure for dexamethasone, PFOS, and atrazine, as did enic ma eS.1Nicotine, PFNA and toluene groups had blood / pressures similar to controls at 56 weeks. n counts revealed significant deficits in the dexamethasone, PFOS, PFNA, and atrazine groups. Kidney glucocorticoid receptor mRNA was elevated in the dexamethasone, PFOS, and atrazine groups. There were no consistent effects on insulin response to oral glucose, nor was there any indication of obesity as indicated by body weights. There were sporadic effects on serum chemistry. Conclusions: Diverse chemical exposures to pregnant rats caused elevated blood pressure in offspring. Lower nephron endowments and elevated glucocorticoid receptor expression may contribute. IUGR and/or maternal stress may be common to all of these exposures. Disclaimer: This abstract does not represent EPA policy.