The Influence of early life vitamin D deficiency on offspring skeletal muscle development, structure and function

Abstract

Vitamin D deficiency (VDD) is highly prevalent in pregnant women, and may impair early life skeletal muscle development, and consequently influence muscle structure and function in adulthood and its rate of decline with aging. The profound decline in muscle mass and strength with age (sarcopenia) is associated with an increased risk of morbidity and mortality. Vitamin D status is determined by dietary intake, sunlight exposure and a deficiency in vitamin D is associated with obesity in humans. There is very little research on how VDD during pregnancy impacts the offspring’s skeletal muscle development, structure and function across the life course. Thus, this thesis aimed to test the hypothesis that pregnancy VDD will impair offspring skeletal muscle development, structure and function across its life course, and this was investigated in animal models of obesity and dietary specific VDD.

In the first study, female C57BL/6J mice were fed a control (C; 7% kcal fat) or high-fat obesogenic (HF; 45% kcal fat) diet 6 weeks prior to mating and throughout pregnancy until weaning. Offspring were fed the C or HF diet postnatally. At 30 weeks of age, offspring isometric muscle contractile parameters, myofibre structure and mRNA levels of genes associated with muscle growth, contraction and insulin signalling were evaluated. In the second study, female C57BL/6J mice were fed a control (C; 1 IU/g vitamin D3) or VDD (0 IU/g vitamin D3) diet from 6 weeks prior to mating until weaning. All offspring were then weaned onto the C diet. At 15-weeks, offspring isometric muscle contractile force, grip strength, overall strength and open-field activity was assessed. In the third study, Welsh mountain ewes were fed a control (C, 2000 IU/kg vitamin D3), or a vitamin D deficient (VDD, 0 IU/kg vitamin D3) diet 17 days prior to conception until 127 days of gestation. In the late-gestation fetus, skeletal muscle radiolabelled glucose uptake, myofibre structure and mRNA levels of insulin signalling genes were quantified.

A pre-weaning obesogenic diet was associated with some effects on muscle contractile peak force and potential fatigability in the adult offspring, and vitamin D homeostasis was affected by maternal obesity. A gestational VDD diet did not alter the skeletal muscle peak force, grip strength or overall strength in the young adult mouse, or glucose uptake in the fetal muscle. However, activity levels were reduced in the VDD mouse adult offspring. Fetal muscle structure did not change following a VDD diet, but some changes to skeletal muscle mass were observed in adulthood in the VDD mouse model.

Overall, the results suggest that VDD during pregnancy is not as detrimental to the offspring’s skeletal muscle as hypothesised at the outset of this thesis. However, reduction in activity levels following a prenatal VDD diet may predispose the offspring to health complications such as obesity and metabolic disorders in later life. Considering there are some changes in muscle mass of offspring following a prenatal VDD diet, determining any myofibre structural changes is required. These data are a novel addition to a small pre-existing body of evidence for a role of pregnancy vitamin D on later life skeletal muscle function, and pave the way for future analysis with the aim to understand how the underlying mechanisms in the offspring muscle are influenced following a VDD diet during pregnancy.

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Identifiers

ORCID for Lucy Green: orcid.org/0000-0001-7423-9696

ORCID for Philip Newland: orcid.org/0000-0003-4124-8507

ORCID for Jane Cleal: orcid.org/0000-0001-7978-4327

ORCID for Kirsten Poore: orcid.org/0000-0002-1455-0615

ORCID for Emiliano Rustighi: orcid.org/0000-0001-9871-7795

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