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Maternal low-protein diet during mouse pre-implantation development induces vascular dysfunction and altered
Adam J Watkins1, Emma S Lucas, Christopher Torrens
1School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, UK. ajw7@soton.ac.uk
Insights
Maternal low-protein diets during pregnancy can lead to high blood pressure in offspring. This study found impaired blood vessel function in male offspring and altered angiotensin-converting enzyme (ACE) activity in both sexes, but kidney development remained unaffected.
Area of Science:
- Developmental biology
- Cardiovascular physiology
- Nutritional science
Background:
- Environmental factors during gestation impact offspring development and health.
- Maternal dietary protein restriction is linked to elevated offspring systolic blood pressure.
- Mechanisms underlying this blood pressure elevation require further investigation.
Purpose of the Study:
- To investigate the mechanisms of blood pressure regulation in offspring exposed to maternal gestational protein restriction.
- To assess arterial vasodilatation, kidney development, and specific gene expression in offspring of mothers on normal-protein (NPD), low-protein (LPD), or early-gestation low-protein (Emb-LPD) diets.
- To evaluate the activity of serum and lung angiotensin-converting enzyme (ACE) in offspring.
Main Methods:
- MF-1 mice dams were fed NPD, LPD, or Emb-LPD diets during gestation.
- Offspring mesenteric arteries were tested for vasodilatation response to isoprenaline.
- Kidney glomerular number was analyzed using stereology.
- Real-time RT-PCR was used to assess gene expression of angiotensin II receptor type 1a, Na+/K+ ATPase, and glucocorticoid receptor.
- Serum and lung ACE activity was measured.
Main Results:
- Male offspring from LPD and Emb-LPD groups showed impaired vasodilatation to isoprenaline.
- No significant differences in kidney glomerular number were observed in female offspring.
- Kidney gene expression for key regulatory factors remained unchanged in both sexes.
- Elevated serum ACE activity was found in LPD females, and elevated lung ACE activity in Emb-LPD males.
Conclusions:
- Maternal gestational protein undernutrition is associated with impaired arterial vasodilatation in male offspring.
- Elevated offspring blood pressure is linked to altered ACE activity in serum (females) and lungs (males).
- Kidney development (glomerular number) and kidney gene expression appear unaffected by these dietary interventions.
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.
