Intra-uterine growth restriction is an independent risk factor for adult psychiatric and cardiovascular diseases. In humans, intra-uterine growth restriction is associated with increased placental and fetal oxidative stress, as well as down-regulation of placental 11β-HSD (11β-hydroxysteroid dehydrogenase). Decreased placental 11β-HSD activity increases fetal exposure to maternal glucocorticoids, further increasing fetal oxidative stress. To explore the developmental origins of co-morbid hypertension and anxiety disorders, we increased fetal glucocorticoid exposure by administering the 11β-HSD inhibitor CBX (carbenoxolone; 12 mg·kg−1 of body weight·day−1) during the final week of murine gestation. We hypothesized that maternal antioxidant (tempol throughout pregnancy) would block glucocorticoid-programmed anxiety, vascular dysfunction and hypertension. Anxiety-related behaviour (conditioned fear) and the haemodynamic response to stress were measured in adult mice. Maternal CBX administration significantly increased conditioned fear responses of adult females. Among the offspring of CBX-injected dams, maternal tempol markedly attenuated the behavioural and cardiovascular responses to psychological stress. Compared with offspring of undisturbed dams, male offspring of dams that received daily third trimester saline injections had increased stress-evoked pressure responses that were blocked by maternal tempol. In contrast, tempol did not block CBX-induced aortic dysfunction in female mice (measured by myography and lucigenin-enhanced chemiluminescence). We conclude that maternal stress and exaggerated fetal glucocorticoid exposure enhance sex-specific stress responses, as well as alterations in aortic reactivity. Because concurrent tempol attenuated conditioned fear and stress reactivity even among the offspring of saline-injected dams, we speculate that antenatal stressors programme offspring stress reactivity in a cycle that may be broken by antenatal antioxidant therapy.
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Research Article|
July 25 2011
Maternal antioxidant blocks programmed cardiovascular and behavioural stress responses in adult mice
Robert D. Roghair;
*Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A.
Correspondence: Dr Robert D. Roghair (email [email protected]).
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John A. Wemmie;
John A. Wemmie
†Department of Psychiatry, University of Iowa, Iowa City, IA 52242, U.S.A.
‡Veterans Affairs Medical Center, Iowa City, IA 52246, U.S.A.
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Kenneth A. Volk;
Kenneth A. Volk
*Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A.
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Thomas D. Scholz;
Thomas D. Scholz
*Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A.
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Fred S. Lamb;
Fred S. Lamb
*Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A.
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Jeffrey L. Segar
Jeffrey L. Segar
*Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A.
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Publisher: Portland Press Ltd
Received:
March 22 2011
Revision Received:
May 11 2011
Accepted:
May 26 2011
Accepted Manuscript online:
May 26 2011
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2011 Biochemical Society
2011
Clin Sci (Lond) (2011) 121 (10): 427–436.
Article history
Received:
March 22 2011
Revision Received:
May 11 2011
Accepted:
May 26 2011
Accepted Manuscript online:
May 26 2011
Citation
Robert D. Roghair, John A. Wemmie, Kenneth A. Volk, Thomas D. Scholz, Fred S. Lamb, Jeffrey L. Segar; Maternal antioxidant blocks programmed cardiovascular and behavioural stress responses in adult mice. Clin Sci (Lond) 1 November 2011; 121 (10): 427–436. doi: https://doi.org/10.1042/CS20110153
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