title: A convergent model for placental dysfunction encompassing combined sub-optimal one-carbon donor and vitamin D bioavailability.
abstract: We hypothesise that the risk of placental dysfunction/insufficiency rises cumulatively in response to several interdependent risk factors that convergently regulate 1,25-dihydroxyvitamin D (the biologically active form of vitamin D, [1,25-(OH)(2)D]) levels at the feto-maternal interface. These factors include; (i) disturbances in genetic or epigenetic regulation of one-carbon metabolism and/or vitamin D metabolism and (ii) insufficiency in maternal vitamin D or in dietary intake of micronutrients that are involved in one-carbon donation. We predict that the sub-optimal functioning of folate and vitamin D metabolic pathways, in concert, represents a potential novel risk pathway for adverse pregnancy outcomes. We base this prediction on five observations: In order to test this model, future epidemiological studies aimed at identifying risk factors for disorders linked to sub-optimal placental development and functioning, should: (a) measure circulating precursor molecules (including folate, vitamin B12, homocysteine, and vitamin D) in maternal and cord blood; (b) collect samples for examination of genotypic variation in both one-carbon and vitamin D regulatory genes and, (c) collect samples for examination of epigenetic status of genes regulating vitamin D homeostasis and action in the placenta.
authors.affiliation: Department of Paediatrics, Developmental Epigenetics, Murdoch Childrens Research Institute, University of Melbourne, Parkville, Victoria 3052, Australia. richard.saffery@mcri.edu.au
authors.forename: Richard
authors.initials: R
authors.lastname: Saffery
authors.forename: Justine
authors.initials: J
authors.lastname: Ellis
authors.forename: Ruth
authors.initials: R
authors.lastname: Morley
mesh_terms: D001682:Biological Availability; D002244:Carbon / Q000378:metabolism*; D005260:Female; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D014807:Vitamin D / Q000493:pharmacokinetics*
chemical_list: D014807:Vitamin D; D002244:Carbon