title: 1,25-Dihydroxy vitamin D3stimulates system A amino acid transport in primary human trophoblast cells.
abstract: Vitamin D deficiency during pregnancy is linked to adverse perinatal outcomes such as small for gestational age infants. Recent evidence suggests that changes in placental amino acid transport contribute to altered fetal growth. We tested the hypothesis that 1,25-dihydroxy vitamin D3increases the gene expression of System A and L amino acid transporter isoforms and stimulates placental amino acid transport activity in cultured primary human trophoblast cells mediated by mTOR signaling. Treatment with 1,25-dihydroxy vitamin D3significantly increased mRNA expression of the System A isoform SNAT2 and System A activity, but had no effect on System L and did not affect mTOR signaling. siRNA silencing of the vitamin D receptor prevented 1,25-dihydroxy vitamin D3-stimulated System A transport. In conclusion, 1,25-dihydroxy vitamin D3regulates System A activity through increased mRNA expression of SNAT2 transporters. Effects on placental amino acid transport may be the mechanism underlying the association between maternal vitamin D status and fetal growth.
authors.affiliation: Division of Reproductive Science, Department of Obstetrics & Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Division of High-risk Pregnancy, Department of Obstetrics & Gynecology, Mackay Memorial Hospital, Taipei, Taiwan. Electronic address: yhyy@mmh.org.tw.
authors.forename: Yi-Yung
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Division of Reproductive Science, Department of Obstetrics & Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Section of Neonatology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Powell
authors.affiliation: Division of Reproductive Science, Department of Obstetrics & Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jansson
mesh_terms: D026924:Amino Acid Transport System A / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism*; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000378:metabolism; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005865:Gestational Age; D006801:Humans; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D026924:Amino Acid Transport System A; D000596:Amino Acids; D034741:RNA, Small Interfering; D018167:Receptors, Calcitriol; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D002762:Cholecalciferol; D058570:TOR Serine-Threonine Kinases
keywords: Fetal growth; Maternal-fetal exchange; Nutrient transport; Placenta