Maternal vitamin D deficiency and developmental origins of health and disease (DOHaD)

Abstract

Vitamin D is an essential nutrient that is metabolized in the body to generate an active metabolite (1,25(OH)2D) with hormone-like activity and highly diverse roles in cellular function. Vitamin D deficiency (VDD) is a prevalent but easily preventable nutritional disturbance. Emerging evidence demonstrates the importance of sufficient vitamin D concentrations during fetal life with deficiencies leading to long-term effects into adulthood. Here, we provide a detailed review and perspective of evidence for the role of maternal VDD in offspring long-term health, particularly as it relates to developmental origins of health and disease (DOHaD). We focus on the roles in neurobehavioral and cardiometabolic disorders in humans and highlight recent findings from zebrafish and rodent models that probe potential mechanisms linking early life VDD to later life health outcomes. Moreover, we explore evidence implicating epigenetic mechanisms as a mediator of this link. Gaps in our current understanding of how maternal VDD might result in deleterious offspring outcomes later in life are also addressed.

Vitamin D deficiency serves as a precursor to stunted growth and central adiposity in zebrafish

“…Vitamin D (1α, 25-dihydroxyvitamin D3) is a steroid hormone traditionally associated with bone homeostasis; however, accumulating evidence suggests a wider biological role for the VD3 signaling axis in metabolic control. Low levels of VD3 during early development have been linked to obesity and metabolic disorders falling under the umbrella of dyslipidemia and adiposity 6 – 12 , 29 . To address the role of vitamin D in metabolic control we developed a dietary VDD model with greater capability of mimicking systemic human VDD than previously published genetic knockout models.…”

“…Several recent studies demonstrate a correlation between low maternal vitamin D levels during pregnancy and small gestational size followed by high BMI’s at one and three years of age 25 . These studies provide initial evidence for an inverse relationship between maternal vitamin D levels and adverse metabolic health outcomes in offspring including excess adiposity and insulin resistance; however, not all studies have demonstrated a definite relationship between VDD and cardiometabolic risk factors in offspring 6 .…”

“…Similar to the increasing incidence of VDD, the occurrence of obesity has tripled since 1975 with nearly two billion obese individuals globally 4 . Both VDD and obesity have been recognized as pandemic, and while the etiology for VDD is well understood, the cause of obesity varies greatly from patient to patient with emerging evidence suggesting that VDD may play an important role 5 , 6 .…”

“…Over the past decade, evidence has linked VDD with low birth weight, small for gestational age, impaired neurodevelopment, autoimmune disease, type 1 and type 2 diabetes (T1D, T2D, respectively), and cardiometabolic dysfunctions including obesity and insulin resistance (IR), suggesting a role for vitamin D in the pathogenesis of metabolic disorders 6 – 13 . Evidence further suggests that elevated levels of vitamin D are associated with a decrease in relative risk for T1D, T2D, hyperglycemia, and IR 14 – 16 .…”

Maternal Liver Metabolic Response to Chronic Vitamin D Deficiency Is Determined by Mouse Strain Genetic Background

“…This study focuses on the liver metabolomic impact of maternal vitamin D deficiency (VDD), a global health concern with some populations having VDD rates >80% ( 25 ). Maternal VDD has major implications for fetal and maternal health ( 26 ). It is well known that VDD impairs human fetal growth and skeletal and extraskeletal health ( 27 – 29 ).…”