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

Adam J. Watkins, Emma S. Lucas, Christopher Torrens, Jane K. Cleal, Lauren Green, Clive Osmond, Judith J. Eckert, William P. Gray, Mark A. Hanson, Tom P. Fleming

Research output: Contribution to journalArticle

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 (3.5d) 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.
Original languageEnglish
Pages (from-to)1762-1770
Number of pages9
JournalBritish Journal of Nutrition
Volume103
Issue number12
Early online date4 Feb 2010
DOIs
Publication statusPublished - Jun 2010

Fingerprint

Protein-Restricted Diet
Renin-Angiotensin System
Blood Vessels
Homeostasis
Mothers
Blood Pressure
Peptidyl-Dipeptidase A
Kidney
Caseins
Vasodilation
Pregnancy
Lung
Angiotensin Type 1 Receptor
Mesenteric Arteries
Dietary Proteins
Glucocorticoid Receptors
Serum
Isoproterenol
Malnutrition
Real-Time Polymerase Chain Reaction

Keywords

  • CVD
  • maternal diet
  • pre-implantation embryo development

Cite this

Watkins, Adam J. ; Lucas, Emma S. ; Torrens, Christopher ; Cleal, Jane K. ; Green, Lauren ; Osmond, Clive ; Eckert, Judith J. ; Gray, William P. ; Hanson, Mark A. ; Fleming, Tom P. / Maternal low-protein diet during mouse pre-implantation development induces vascular dysfunction and altered renin-angiotensin-system homeostasis in the offspring. In: British Journal of Nutrition. 2010 ; Vol. 103, No. 12. pp. 1762-1770.
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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 (3.5d) 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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Watkins, AJ, Lucas, ES, Torrens, C, Cleal, JK, Green, L, Osmond, C, Eckert, JJ, Gray, WP, Hanson, MA & Fleming, TP 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, vol. 103, no. 12, pp. 1762-1770. https://doi.org/10.1017/S0007114509993783

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, Mark A.; Fleming, Tom P.

In: British Journal of Nutrition, Vol. 103, No. 12, 06.2010, p. 1762-1770.

Research output: Contribution to journalArticle

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T1 - Maternal low-protein diet during mouse pre-implantation development induces vascular dysfunction and altered renin-angiotensin-system homeostasis in the offspring

AU - Watkins, Adam J.

AU - Lucas, Emma S.

AU - Torrens, Christopher

AU - Cleal, Jane K.

AU - Green, Lauren

AU - Osmond, Clive

AU - Eckert, Judith J.

AU - Gray, William P.

AU - Hanson, Mark A.

AU - Fleming, Tom P.

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