Maternal Vitamin D Deficiency Impairs the Development of β Cells in Offspring Rats in a Sex-Dependent Manner

• Published in: International journal of molecular sciences Vol. 25; no. 8; p. 4136
• Main Authors: Schavinski, Aline Z, Reis, Natany G, Morgan, Henrique J N, Assis, Ana Paula, Moro, Matheus L, Valentim, Rafael R, Seni-Silva, Ana Carolina, Ramos, Ester S, Kettelhut, Isis C, Navegantes, Luiz C C
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.04.2024
• Subjects: Alfacalcidol; Animals; Calcifediol; Cell cycle; Female; Females; fetal programming; Fetus; Glucose; Growth; Homeostasis; Insulin - blood; Insulin - metabolism; Insulin resistance; Insulin Secretion; Insulin-Secreting Cells - metabolism; Male; Males; Metabolism; Metabolites; Pancreas; Pancreatic beta cells; Physiological aspects; Pregnancy; Prenatal Exposure Delayed Effects - etiology; Prenatal Exposure Delayed Effects - metabolism; Rats; Rats, Wistar; Scientific equipment and supplies industry; Sex Factors; Sexes; sexual dimorphism; Type 2 diabetes; Vitamin D; Vitamin D Deficiency - metabolism; Vitamin deficiency; Weaning; β cell function; Brazil; United States; fetal programming; vitamin D; β cell function; sexual dimorphism
• DOI: 10.3390/ijms25084136
• ISSN: 1422-0067; 1661-6596

Recent studies have shown that maternal vitamin D deficiency (VDD) causes long-term metabolic changes in offspring. However, little is known about the impact of maternal VDD on offspring endocrine pancreas development and insulin secretion in the adult life of male and female animals. Female rats (Wistar Hannover) were fed either control (1000 IU Vitamin D3/kg), VDD (0 IU Vitamin D3/kg), or a Ca -enriched VDD diet (0 IU Vitamin D3/kg + Ca and P/kg) for 6 weeks and during gestation and lactation. At weaning, VDD status was confirmed based on low serum calcidiol levels in dams and pups. Next, male and female offspring were randomly separated and fed a standard diet for up to 90 days. At this age, serum calcidiol levels were restored to normal levels in all groups, but serum insulin levels were decreased in VDD males without affecting glucagon levels, glycemia, or glucose tolerance. Islets isolated from VDD males showed lower insulin secretion in response to different glucose concentrations, but this effect was not observed in VDD females. Furthermore, VDD males, but not females, showed a smaller total pancreatic islet area and lower β cell mass, an effect that was accompanied by reduced gene expression of , , , and . The decrease in expression was not related to the methylation profile of the promoter region of this gene. Most of these effects were observed in the male VDD+Ca group, indicating that the effects were not due to alterations in Ca metabolism. These data show that maternal VDD selectively impairs the morphology and function of β cells in adult male offspring rats and that female offspring are fully protected from these deleterious effects.