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Review
. 2019 Mar 1:JOE-18-0541.R2.
doi: 10.1530/JOE-18-0541. Online ahead of print.

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

Folami Y Ideraabdullah  1 , Anthony M Belenchia  2 , Cheryl Susan Rosenfeld  3 , Seth W Kullman  4 , Megan Knuth  5 , Debrata Mahapatra  6 , Michael Bereman  7 , Edward D Levin  8 , Catherine Ann Peterson  9
Affiliations
Review

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

Folami Y Ideraabdullah et al. J Endocrinol. .

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 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.

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Conflict of interest statement

Disclosures: The authors have no conflicts of interest to disclose

Figures

Figure 1.
Figure 1.
Synthesis and functions of active hormonal vitamin D metabolite 1,25(OH)2D. As shown, the liver is essential in converting vitamin D to 25(OH)D. Within the kidney, it is then further metabolized to 1,25(OH)2D, although it is increasingly being recognized that other organs can convert 25(OH)D to 1,25(OH)2D. Once formed, 1,25(OH)2D can induce both genomic and non-genomic effects mediated by VDR, some of which are illustrated in this diagram. (Modified from (Vuolo et al. 2012; Lim & Kim 2014)).
Figure 2.
Figure 2.
Model of in utero VDD-induced epigenetic effects on long-term health outcomes in offspring. Potential pathway of events connecting maternal vitamin D deficiency to offspring health outcomes via epigenetically regulated organ/tissue dysfunction. Decreased availability of maternal 25(OH)D leads to decreased 25(OH)D entering the placenta and thus decreased availability of the 1,25(OH)2D required for genomic (VDR) and non-genomic signaling responses in the fetus. Consequently, fetal VDD potentially disrupts epigenetic programming during development of target organs/tissues such as brain, liver, and adipose tissue. Dysregulated epigenetic programming leads to long term altered epigenetic states, which as shown, can disrupt genomic accessibility of regulatory machinery and downstream gene expression resulting in adverse long-term health outcomes in offspring, including neurobehavioral and metabolic disorders.
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