Elevated Blood Pressure in Offspring of Rats Exposed to Diverse Chemicals During Pregnancy

Abstract

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.

Perfluorononanoic acid (PFNA) alters lipid accumulation in bovine blastocysts after oocyte exposure during in vitro maturation

“…No comparable studies using the IVP model are available. Exposure in PFNA 0.1 is consistent with lowdose in vitro exposure [17] and significantly lower than the dose measured in mouse serum after oral administration [44,46,48].…”

“…In contrast, no statistical difference was found in lipid droplets with a diameter of 9-12 µm (p=0.09, Table 3). Previous studies have investigated the developmental toxicity of PFNA using laboratory animals like rodents and zebrafish [16][17][18][44][45][46][47]. In this study, we have examined endpoints of developmental toxicity using the bovine IVP as a model, exposing oocytes during 22h maturation in vitro to either 10 µg mL -1 PFNA (PFNA 10) or 0.1 µg mL -1 PFNA (PFNA 0.1).…”

A novel mechanism underlies atrazine toxicity in quails (Coturnix Coturnix coturnix): triggering ionic disorder via disruption of ATPases

“…The changes of contents of K + of experimental group in the liver were more obvious than heart's, suggesting that atrazine could disorder K + content directly via influencing Na + -K + -ATPase activities. Moreover, atrazine caused cardiac, hepatic, nephric dysfunction, activated renin-angiotensin-aldosterone system, boosted levels of aldosterone [55]. The role of aldosterone is to promote K + excretion and Na + reabsorption.…”

Sex differences in major depression and comorbidity of cardiometabolic disorders: impact of prenatal stress and immune exposures

“…Specifically, fetal increases in GCs can program changes in cardiovascular function in male and female rodent offspring, resulting in adulthood in increased vascular sensitivity to norepinephrine [180,181], neuropeptide Y [182], electrical field stimulation [182], increased peripheral resistance, and reduced cardiac output [183]. With respect to blood pressure, both hypertension [184,185] and hypotension [180,186] have been reported. Moreover, adult offspring of prenatally stressed dams were more susceptible to elevations in blood pressure in response to high salt diet [187], angiotensin II (Ang II) [181], and restraint [180,182,188] suggesting the coincident programming of other physiological systems as well.…”