Citation:

Rogers, J., R. Ellis-Hutchings, Brian E. Grey, Robert M. Zucker, J. Norwood, C. Grace, C. Gordon, AND C. Lau. Elevated blood pressure in offspring of rats exposed to diverse chemicals during pregnancy. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 137(2):436-46, (2014). https://doi.org/10.1093/toxsci/kft248

Impact/Purpose:

Adverse intrauterine environments are associated with increased risk of later disease, including cardiovascular disease and hypertension. We measured blood pressure (BP), renal neplron endowment, renal glucocorticoid receptor (GR) gene expression, and serum aldosterone in offspring of pregnant Sprague-Dawley rats exposed to dexamethasone (Dex), perfluorooctane sulfonate (PFOS), atrazine, perfluorononanoic acid (PFNA), arsenic or nicotine. BP was higher in Dex, PFOS, atrazine and PFNA male offspring by 7-10 weeks of age. Female offspring exhibited elevated BP at 10 weeks for PFNA and arsenic, and at 37 weeks for Dex, PEOS and atrazine. Male and female Dex, PFOS and atrazine offspring still exhibited elevated BP at 52-65 weeks of age; others did not. Elevated BP was associated with lower nephron counts. Dex, PFOS and atrazine offspring also had elevated renal GR gene expression. Elevated BP in the Dex and atrazine offspring was confirmed by radiotelemetry and atrazine offspring exhibited enhanced CORT response to restraint. Elevated BP in offspring was induced by maternal exposure to diverse toxicants. Since all treatments affected maternal gestational weight gain, maternal stress may be a common underlying factor in these observations. These findings suggest that blood pressure, and perhaps renal development, may be sensitive indicators of an adverse prenatal environment.

Description:

Adverse intrauterine environments have been associated with increased risk of later cardiovascular disease and hypertension. In an animal model using diverse developmental toxicants, we measured blood pressure (BP), renal nephron endowment, renal glucocorticoid receptor (GR) gene expression, and serum aldosterone in offspring of pregnant Sprague Dawley rats exposed to dexamethasone (Dex), perfluorooctane sulfonate (PFOS), atrazine, perfluorononanoic acid (PFNA), arsenic, or nicotine. BP was assessed by tail cuff photoplethysmography, nephron endowment by confocal microscopy, and renal GR mRNA by qPCR. BP was also measured by telemetry, and corticosterone (CORT) was measured in resting or restrained Dex and atrazine offspring. Treated dams gained less weight during treatment in all groups except arsenic. There were chemical- and sex-specific effects on birth weight, but offspring body weights were similar by weaning. BP was higher in Dex, PFOS, atrazine, and PFNA male offspring by 7–10 weeks. Female offspring exhibited elevated BP at 10 weeks for PFNA and arsenic, and at 37 weeks for Dex, PFOS, and atrazine. Dex, PFOS, and atrazine offspring still exhibited elevated BP at 52–65 weeks of age; others did not. Elevated BP was associated with lower nephron counts. Dex, PFOS, and atrazine offspring had elevated renal GR gene expression. Elevations in BP were also observed in Dex and atrazine offspring by radiotelemetry. Atrazine offspring exhibited enhanced CORT response to restraint. Elevated offspring BP was induced by maternal exposure to toxicants. Because all treatments affected maternal gestational weight gain, maternal stress may be a common underlying factor in these observations.

URLs/Downloads:

Record Details: