Gene Expression of Vitamin D Regulatory Enzymes in Renal Tissue of Growing Pigs is Modulated by Maternal Dietary Vitamin D Concentrations

The relationship between maternal dietary vitamin D (D) and offspring development is recognized, but not completely understood. Most human studies focus on skeletal densitometry and serum 25‐OH D 3 as these are less invasive methods which reflect D status. Animal models provide an advantage in that both gross and molecular analyses are possible. We have developed a kyphotic pig model by feeding maternal diets deficient in D during gestation and lactation followed by neonatal pig diets deficient in D, and marginally limited in Ca and P. This model has provided a means to study maternal dietary D carryover effects on bone and soft tissue traits in neonatal and growing pigs. As previously reported, growth was reduced by 11% and bone mineral density by 25% if pigs were produced by sows fed no D, regardless of neonatal diet. Molecular analysis of bone and soft tissue from these pigs will aid in further mechanistic understanding of the carryover responses. The current results are an analysis of maternal and neonatal diet effects on a subset of genes involved in the activation (1α‐hydroylase; CYP27B1) and catabolism (25‐hydroxylase; CYP24A1) of D in kidney tissue (KD). Sows were fed diets with 0 (−D), 325 (+D) or 1750 (++D) IU D 3 /kg (n = 12, 12, or 13/diet). At weaning (3 wk) pigs were fed diets with 0 (−D) or 280 (+D) IU D 3 /kg, each with 75% and 95% (LCaP) or 150% and 120% (HCaP) of the Ca and P requirements, respectively. Pigs were killed prior to colostrum consumption at birth (n = 27), weaning (3 wk; n = 27), and after the nursery period (8 wk; n = 71). Data were normalized to the geometrical mean of hypoxanthine phosphoribosyltransferase (HPRT1), ribosomal protein S18 (RPS18), and cyclophilin A (CYCLOA). No differences in KD mRNA expression of CYP24A1 or CYP27B1 were detected at birth. At weaning KD mRNA expression of CYP24A1 was increased 9‐fold in pigs produced by ++D sows while expression of CYP27B1 was decreased to 0.4‐fold in pigs produced by +D or ++D sows. At 8 wk pigs fed +D nursery diets had a 2.75‐fold increase in KD mRNA expression of CYP24A1 and expression of CYP27B1 reduced to 0.4‐fold. More intriguing were the maternal dietary D effects evident at 8 wk regardless of neonatal diet. At 8 wk KD mRNA expression of CYP24A1 was increased 3‐fold in pigs produced by ++D sows. Concomitantly KD mRNA expression of CYP27B1 was reduced to 0.7‐fold in pigs produced by +D and ++D sows. Overall, an increase in dietary D induced an increase in CYP24A1 while simultaneously inducing a decrease in CYP27B1, as expected. Serum from pigs at birth, 3, and 8 wk revealed modest increases in 25‐OH D 3 due to dietary D. Pigs produced by ++D sows at 3 wk and pigs from these litters fed +D neonatal diets at 8 wk had the greatest concentrations of serum 25‐OH D 3 (5 ng/mL). Serum 25‐OH D 3 responses across treatment groups implied that large magnitudes of dietary modifications were not necessary to evoke regulation of D demonstrated by molecular changes in the KD. The results reported herein illustrate that maternal carryover effects are not only evident in whole animal responses, but also at a molecular level. Additional analysis of genes involved in D metabolism and D‐mediated bone development are needed to further characterize effects of maternal dietary D on offspring skeletal abnormalities observed in the kyphotic pig model. Support or Funding Information Appreciation expressed to DSM Nutritional Products for serum analysis