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Hypocalcemic, hypophosphatemic rickets in rat pups suckling vitamin D-deprived mothers
Insights
Maternal vitamin D deficiency in rats causes biochemical and histological changes in pups, mimicking human rickets. This highlights the critical role of maternal vitamin D for offspring skeletal health.
Area of Science:
- Nutritional biochemistry
- Developmental biology
- Pediatric pathology
Background:
- Maternal nutrition significantly impacts offspring development.
- Vitamin D is crucial for calcium and phosphorus homeostasis and bone health.
- Vitamin D deficiency in humans causes rickets, but its effects via maternal transfer in early life are less understood.
Purpose of the Study:
- To investigate the effects of maternal vitamin D deprivation on rat pups.
- To assess biochemical markers (serum Ca, P, 250HD3, Mg) and bone histology in pups.
- To compare the effects of in-utero/suckling deprivation versus post-weaning deprivation.
Main Methods:
- Pregnant rats were fed diets with or without vitamin D.
- Rat pups were studied at various ages (5-57 days) for serum mineral levels and bone ash content.
- Histological examination of long bones (tibia) was performed.
Main Results:
- Pups of vitamin D-deprived mothers showed reduced serum P and 250HD3 by 8 days.
- By 15 days, pups had undetectable 250HD3, reduced body weight, serum Ca, and serum P.
- Histology revealed widened hypertrophic cartilage and altered trabeculae, indicative of rickets.
Conclusions:
- Rat pups suckling vitamin D-deprived mothers develop biochemical and histological evidence of vitamin D deficiency rickets.
- Maternal vitamin D status is critical for preventing rickets in early life.
- Unlike post-weaning deprivation, maternal deprivation leads to hypophosphatemia and characteristic rickets histology.
Abstract:
The effects of maternal vitamin D deprivation on rat pups were examined in terms of serum levels of Ca, phosphorus (P), and 25-hydroxyvitamin D (250HD), ash content, and histological appearance of long bones. In each of 10 experiments, litters of 8--10 young were examined at 2 or 3 different ages within the range of 5--57 days. Pregnant mothers were fed a diet containing 0.4% Ca, and 0.4% P and either no vitamin D(--D) or 5 IU D3/g diet (+D). Mothers fed the --D diet developed marked hypocalcemia (4--5 mg/dl) during lactation, but no change in milk Ca or P. The earliest changes in pups suckled by mothers on --D diets compared to pups suckled by mothers on +D diets were significant reductions at 8 days in serum P (6--12% in 3 of 5 experiments) and in serum 250HD3. By the 15th day, serum 250HD3 was undetectable, body weight was reduced by 26%, serum Ca was reduced by 9%, and serum P was reduced by 15%. During the following 10 days, when gradual weaning took place, serum Ca decreased progressively, serum P returned to normal, serum Mg became elevated, bone ash (as percent of dry weight of tibia) was decreased, and decalcified sections of the proximal end of the tibia revealed irregularity and widening (1.5- to 3-fold) of the hypertrophic cartilage layer and the metaphyseal trabeculae. All of these changes were also prominent in 8-week-old --D rats. The results indicate that rat pups suckling vitamin D-deprived mothers can develop biochemical evidence (including hypophosphatemia) as well as histological evidence of vitamin D deficiency similar to that of human vitamin D deficiency rickets. This is in contrast to rats deprived of vitamin D after weaning, who do not develop hypophosphatemia or characteristic histological evidence of rickets unless deprived of P as well as vitamin D.