Maternal Vitamin D Deficiency During Pregnancy Alters Hepatic Metabolism in Adult Female Offspring Without Overt Metabolic Dysfunction

Background/Objectives: Vitamin D deficiency (VDD) is a major global health concern. Although maternal VDD during pregnancy may influence metabolic health in offspring, previous studies have focused predominantly on male offspring, leaving its effects in females insufficiently characterized. This study aimed to comprehensively assess hepatic metabolic profiles in female offspring exposed to maternal VDD during gestation. Methods: Pregnant 129/Sv mice were fed either a control diet or a vitamin D-deficient diet throughout pregnancy. After weaning, female offspring were maintained on a normal diet and analyzed at 12 weeks of age following a 16 h fast. Hepatic metabolomic profiling was conducted using GC–MS/MS, followed by multivariate analysis. To evaluate the potential contribution of fasting, publicly available liver RNA-seq data from ad libitum-fed and 16 h-fasted mice (GSE130127) were also analyzed. Results: No overt metabolic abnormalities were detected between the groups. However, principal component analysis revealed differences in hepatic metabolic profiles between the Control and VDD groups. Levels of 4-aminobutyric acid and proline were significantly elevated in the VDD group. Pathway analysis revealed significant alterations in arginine and proline metabolism and purine metabolism, along with changes in pathways associated with amino acid and energy metabolism. Comparison with fasting-associated liver RNA-seq data revealed minimal overlap, although the potential influence of fasting cannot be completely excluded. Conclusions: Maternal VDD during pregnancy was associated with altered hepatic metabolic profiles in female offspring despite the absence of overt metabolic abnormalities. These findings suggest that maternal VDD may influence hepatic metabolism in female offspring and indicate that the potential long-term effects of maternal VDD on offspring metabolism warrant further investigation.