The rate of collagen biosynthesis is high during fetal development. Adequate collagen production in utero is very important for normal development of the skeleton and of tissues containing high quantities of collagen. Since ascorbic acid (AA) directly influences collagen production, an inadequate intake of AA by the dam may result in an insufficient AA supply, thereby compromising fetal development. At the other extreme, a very high maternal intake of AA may result in pharmacological rather than nutritional effects which may inhibit or alter in utero development. The objective of the proposed project is to examine the impact of maternal AA intake on fetal development, including skeletal development and collagen production in tissues. Skeletal development of pups and bone remodeling of dams will be evaluated by determinations of length, diameter, density, mineralization, and mineral to matrix ratio of tibiae and vertebrae. The capacity to produce collagen will be evaluated in vitro using fetal calvarial bone. Collagen production will also be assessed in offspring by biochemical and morphometric analysis of tissues that are high in collagen (tendon and skin). First, dams will be on a controlled AA intake that is very low (0.05 g/kg diet), low (0.15 g/kg diet), normal (0.50 g/kg diet), high (2 g/kg diet), or excess (10 g/kg diet) starting at least 3 wk prior to mating and held constant throughout gestation and after birth (Specific Aim # 1). Second, maternal AA intake will be changed abruptly and markedly during early and later phases of gestation in order to assess if there is a critical time for an adequate AA supply for the fetus (Specific Aim 1 #2). Tissues will be examined from fetuses at middle (gestational day 40) and late (gestational day 55) times during the 63-72 days of gestation and from pups at birth and at 2 wk after birth. Results of these studies will enhance our understanding of the impact of consuming very low to very high intakes of AA during pregnancy on the developing fetus. Results of these studies will indicate the extent to which maternal AA intake influences skeletal development and tissue collagen production of the fetus when maternal AA intake is at a constant level or altered significantly during gestation. Results will also provide evidence to support recommendations for the level of AA needed during pregnancy to optimize fetal growth and development.
| Kipp, D E; McElvain, M; Kimmel, D B et al. (1996) Scurvy results in decreased collagen synthesis and bone density in the guinea pig animal model. Bone 18:281-8 |
| Kipp, D E; Grey, C E; McElvain, M E et al. (1996) Long-term low ascorbic acid intake reduces bone mass in guinea pigs. J Nutr 126:2044-9 |
