Effect of modest vitamin A deficiency in pregnant rats on bone mass and metabolic parameters in the offspring

Vitamin A deficiency is a serious public health problem worldwide, affecting more than 100 countries. The most severe effects of this deficiency are seen in young children and pregnant women in low-income countries, especially Africa and South Asia. In a study among 855 pregnant, healthy Norwegian women, we observed vitamin A inadequacy in a substantial proportion of women (about 40%) in third trimester. A lack of vitamin A weakens a child’s immune system, putting them at greater risk of disease and early death. Vitamin A deficiency is also the leading cause of preventable child blindness. Moreover, vitamin A is important for skeletal development and maintenance of bone health. Studies in rodents have shown that vitamin A is crucial for development of the skeleton, both deficiency and excess causing skeletal defects. We have previously shown a positive association between vitamin A levels in pregnant women and offspring bone mass at the age of 26 years. This may translate to increased risk of osteoporosis and fractures in the future. A relationship between maternal vitamin A level and metabolic syndrome/diabetes in offspring later in life has also been found. These observations have been postulated to be attributed to epigenetic modifications. Animal studies are required to test whether these associations are due to a causal connection between exposure to hypovitaminosis A in fetal life and future osteoporosis and metabolic disease in the offspring. To explore this, we intend to induce a state of vitamin A inadequacy or modest deficiency in female Sprague Dawley rats pre-pregnancy. The modest vitamin A deficiency will be controlled by measurements of serum retinol, with a total of up to 14 blood samples (maximum 1 ml blood drawn with minimum 2 weeks separation)-To our knowledge, similar studies have not been conducted in animals before. Ten female rats that will be assigned to two groups pre pregnancy and given a diet deficient and not deficient in vitamin A, respectively. Their offspring, estimated to be 50 in each group will be followed after birth. Assessment of bone and metabolic parameters in the offspring will be performed one week after birth, after weening period is over (3 weeks) and after 12 weeks. The vitamin A deficiency that is induced is modest, thus we do not expect substantial adverse effects in neither mother nor offspring. This study will provide novel insight into the role of vitamin A in developmental origin of disease. Verification of the findings from epidemiological studies may promote supplementation of vitamin A to pregnant women, thus contributing to reduce the burden of osteoporotic fractures and metabolic disease in their children. Given the high prevalence of vitamin A deficiency among pregnant women worldwide this may have major consequences for public health.