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Maternal low-protein diet during mouse pre-implantation development induces vascular dysfunction and altered renin-angiotensin-system homeostasis in the offspring

Watkins, Adam J., Lucas, Emma S., Torrens, Christopher, Cleal, Jane K., Green, Lauren, Osmond, Clive, Eckert, Judith J., Gray, William P., Hanson, M.A. and Fleming, Tom P. (2010) Maternal low-protein diet during mouse pre-implantation development induces vascular dysfunction and altered renin-angiotensin-system homeostasis in the offspring British Journal of Nutrition, 103, (12), pp. 1762-1770. (doi:10.1017/S0007114509993783). (PMID:20128937).

Record type: Article

Abstract

Environmental perturbations during early mammalian development can affect aspects of offspring growth and cardiovascular health. We have demonstrated previously that maternal gestational dietary protein restriction in mice significantly elevated adult offspring systolic blood pressure. Therefore, the present study investigates the key mechanisms of blood pressure regulation in these mice. Following mating, female MF-1 mice were assigned to either a normal-protein diet (NPD; 18 % casein) or an isocaloric low-protein diet throughout gestation (LPD; 9 % casein), or fed the LPD exclusively during the pre-implantation period (3.5 d) before returning to the NPD for the remainder of gestation (Emb-LPD). All offspring received standard chow. At 22 weeks, isolated mesenteric arteries from LPD and Emb-LPD males displayed significantly attenuated vasodilatation to isoprenaline (P = 0.04 and P = 0.025, respectively), when compared with NPD arteries. At 28 weeks, stereological analysis of glomerular number in female left kidneys revealed no significant difference between the groups. Real-time RT-PCR analysis of type 1a angiotensin II receptor, Na+/K+ ATPase transporter subunits and glucocorticoid receptor expression in male and female left kidneys revealed no significant differences between the groups. LPD females displayed elevated serum angiotensin-converting enzyme (ACE) activity (P = 0.044), whilst Emb-LPD males had elevated lung ACE activity (P = 0.001), when compared with NPD offspring. These data demonstrate that elevated offspring systolic blood pressure following maternal gestational protein undernutrition is associated with impaired arterial vasodilatation in male offspring, elevated serum and lung ACE activity in female and male offspring, respectively, but kidney glomerular number in females and kidney gene expression in male and female offspring appear unaffected.

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More information

e-pub ahead of print date: 4 February 2010
Keywords: cvd, maternal diet, pre-implantation embryo development
Organisations: Faculty of Medicine, Centre for Biological Sciences

Identifiers

Local EPrints ID: 145213
URI: http://eprints.soton.ac.uk/id/eprint/145213
ISSN: 0007-1145
PURE UUID: afe5bde2-4961-4b46-b274-4dc665925ea9
ORCID for Clive Osmond: ORCID iD orcid.org/0000-0002-9054-4655

Catalogue record

Date deposited: 21 Apr 2010 12:52
Last modified: 18 Jul 2017 23:06

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Contributors

Author: Adam J. Watkins
Author: Emma S. Lucas
Author: Jane K. Cleal
Author: Lauren Green
Author: Clive Osmond ORCID iD
Author: William P. Gray
Author: M.A. Hanson
Author: Tom P. Fleming

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