EPA Science Inventory

Elevated blood pressure in offspring of rats exposed to diverse chemicals during pregnancy

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, 137(2):436-46, (2014).

Description:

Adverse intrauterine environments are associated with increased risk of later disease, including cardiovascular disease and hypertension. As a potential bioindicator of such an adverse environment, 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 flex and atrazine offspring. Treated dams gained less weight during treatment in all groups except arsenic. Dex and PFNA offspring had lower birth weights, 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 also had elevated renal GR gene expression. Similar elevations in BP were 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. Since all treatments affected maternal gestational weight gain, maternal stress may be a common underlying factor in these observations.

Purpose/Objective:

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.

URLs/Downloads:

TAD-13-062-ABSTRACT.PDF   (PDF,NA pp, 217.803 KB,  about PDF)

Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Start Date: 04/17/2014
Completion Date: 04/17/2014
Record Last Revised: 08/08/2014
Record Created: 04/17/2014
Record Released: 04/17/2014
OMB Category: Other
Record ID: 273551

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB

TOXICOLOGY ASSESSMENT DIVISION