Elevated blood pressure in offspring of rats exposed to diverse chemicals during pregnancy.
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.
Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
John M
JM
Rogers
Robert G
RG
Ellis-Hutchings
Brian E
BE
Grey
Robert M
RM
Zucker
Joel
J
Norwood
Curtis E
CE
Grace
Christopher J
CJ
Gordon
Christopher
C
Lau
D000450:Aldosterone / Q000097:blood; D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D005260:Female; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D018613:Microscopy, Confocal; D009399:Nephrons / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis; D013315:Stress, Psychological / Q000097:blood; D015262:Xenobiotics / Q000737:chemistry / Q000633:toxicity*
D011965:Receptors, Glucocorticoid; D015262:Xenobiotics; D000450:Aldosterone
DOHaD; fetal physiology; fetal programming; maternal stress.; maternal toxicity