Mechanisms Of Vitamin A Delivery To Mammary Milk And Offspring In Mice
Creators: Richardson, Jenna
Publisher: name: University of Alberta Library
Year: 2023

<p>Background: Vitamin A status is an important health determinant. Deficiency of this micronutrient is a serious global health issue in the developing nations as the leading cause of preventable blindness in children and is a significant contributor to long-term morbidity and mortality. Nutritional demands for vitamin A are highest during pregnancy and lactation. This period is important for establishing offspring’s vitamin A reserves critical for long-term health. <br>
Aim: Our overall objective was to better understand the mechanisms underlying the delivery of vitamin A to maternal milk and offspring in mice. This included an analysis of: 1) maternal vitamin A homeostasis during lactation, with a focus on the mammary gland, and 2) genetic, and 3) dietary intervention studies designed to dissect the contribution of maternal vitamin A stores and dietary vitamin A intake in the establishment of vitamin A reserves in offspring. <br>
Methods: All studies were conducted in mice. In Chapter 3, the mammary gland and other tissues were collected from virgin, lactating and involuting mice, followed by an assessment of gene expression (qPCR) and tissue vitamin A concentrations (HPLC). In Chapter 4, wild-type pregnant mice were split into two groups, one receiving a diet with 25 IU vitamin A/g, and one receiving a vitamin A deficient diet (0 IU vitamin A/g), during pregnancy and lactation. Tissues were collected from offspring at (postnatal day [P]1), during lactation (P7), at weaning (P21), two weeks post-weaning (P35), P70 and P105 with vitamin A concentrations measured by HPLC. In Chapter 5, tissues were collected from the offspring of wild-type and Lrat-/- female mice at P1, P7 and P21 vitamin A concentrations were measured (HPLC).<br>
Results: In Chapter 3 we observed a shift in the expression pattern of the vitamin A metabolic pathway in the mammary gland of lactating mice. Most prominently, there was a significant increase in the expression of the retinyl ester-synthesizing enzyme Lrat during lactation, which returned to baseline following involution. In Chapter 4, our results show a direct relationship between maternal vitamin A intake and offspring liver retinol and retinyl ester reserves. Offspring from dams consuming a vitamin A deficient diet had consistently lower hepatic vitamin A levels than control at P7, P21, and P35, which returned to control group concentrations at P70 (adulthood). In Chapter 5, we observed no significant differences in the hepatic vitamin A status of heterozygous offspring born to wild-type and Lrat-/- female, despite Lrat-/- female lacking hepatic vitamin A stores.<br>
Conclusion: We have characterized pronounced changes in the vitamin A metabolic pathway in the mammary gland of lactating mice, consistent with the role of LRAT as the primary enzyme responsible for retinyl ester incorporation into milk. Our study further supports the hypothesis that maternal dietary vitamin A intake is critical in establishing adequate vitamin A reserves in offspring and suggests that maternal hepatic stores cannot compensate for a lack of maternal dietary vitamin A. Moreover, vitamin A sufficient pups accumulate hepatic vitamin A stores with time, which is hindered in pups with dams on a vitamin A deficient diet and persists until early adulthood despite the introduction of adequate dietary intake after weaning. </p>