Placental amino acid transport may be regulated by maternal vitamin D and vitamin D-binding protein: results from the Southampton Women's Survey

Abstract

Both maternal 25-hydroxyvitamin D (25(OH)D) concentrations during pregnancy and placental amino acid transporter gene expression have been associated with development of the offspring in terms of body composition and bone structure. Several amino acid transporter genes have vitamin D response elements in their promoters suggesting the possible linkage of these two mechanisms. We aimed to establish whether maternal 25(OH)D and vitamin D-binding protein (VDBP) levels relate to expression of placental amino acid transporters. RNA was extracted from 102 placental samples collected in the Southampton Women's Survey, and gene expression was analysed using quantitative real-time PCR. Gene expression data were normalised to the geometric mean of three housekeeping genes, and related to maternal factors and childhood body composition. Maternal serum 25(OH)D and VDBP levels were measured by radioimmunoassay. Maternal 25(OH)D and VDBP levels were positively associated with placental expression of specific genes involved in amino acid transport. Maternal 25(OH)D and VDBP concentrations were correlated with the expression of specific placental amino acid transporters, and thus may be involved in the regulation of amino acid transfer to the fetus. The positive correlation of VDBP levels and placental transporter expression suggests that delivery of vitamin D to the placenta may be important. This exploratory study identifies placental amino acid transporters which may be altered in response to modifiable maternal factors and provides a basis for further studies.

1,25-Dihydroxy vitamin D3 stimulates system A amino acid transport in primary human trophoblast cells

“…1,25-dihydroxy vitamin D 3 achieves this coordination by inducing innate antibacterial responses in human trophoblasts and inhibiting pro-inflammatory cytokines such as TNF-α and IL-6 (Liu et al, 2009; Noyola-Martinez et al, 2013). Although Cleal and colleagues recently identified an association between maternal serum 25-hydroxy vitamin D 3 concentrations and placental gene expression of amino acid transporters (Cleal et al, 2015), to the best of our knowledge vitamin D regulation of placental amino acid transporter activity has not previously been reported.…”

“…Recently, a study from the Southampton Women's survey demonstrated that maternal 25-hydroxyvitamin D and vitamin D binding protein levels were positively associated with placental expression of several amino acid transporter genes, suggesting placental amino acid transport may be regulated by maternal vitamin D and/or vitamin D-binding protein (Cleal et al, 2015). Previous studies in murine skeletal myotubes have shown that vitamin D enhances protein synthesis through mechanistic target of rapamycin (mTOR) signaling pathway (Salles et al, 2013) and we have reported that mTOR signalling is a positive regulator of amino acid transport in cultured primary human trophoblast (PHT) cells (Rosario et al, 2013).…”

Clinical Utility of Measurement of Vitamin D-Binding Protein and Calculation of Bioavailable Vitamin D in Assessment of Vitamin D Status

“…Several studies have shown that vitamin D deficiency correlates with various clinical conditions and parameters, including osteoporosis, cardiovascular diseases, autoimmune diseases, schizophrenia, surgical outcomes, and cancer risk [1213141516171819]. Nonetheless, the causality is still unproven.…”

Early‐life dietary and epigenetic influences on childhood musculoskeletal health: Update on the UK component of the ALPHABET project

“…, ); mechanistic investigations using placental samples have identified novel relationships between vitamin D and placental nutrient transport (Cleal et al . ).…”

“…The results of this trial suggest that such a supplementary approach leads to improved offspring bone mineral content (of around 0.5 SD) compared with placebo, for neonates born in the winter months, when background 25(OH)D concentrations are lowest (although not in the population overall) . Subsequent work has identified interactions with both environmental and genetic factors in the achieved 25 (OH)D in response to treatment (Moon et al , 2017; mechanistic investigations using placental samples have identified novel relationships between vitamin D and placental nutrient transport (Cleal et al 2015). These candidate-focused studies contrast with findings from a recent investigation using the Illumina Human Methylation 450 BeadChip, an array covering methylation marks at over 450 000 CpG sites across the genome.…”