title: Placental vitamin D receptor expression is decreased in human idiopathic fetal growth restriction.
abstract: Fetal growth restriction (FGR) affects up to 5 % of pregnancies worldwide, and trophoblast function plays a significant role on the outcome. An epidemiological study has linked vitamin D deficiency to adverse perinatal outcomes, which include decreased birth weight. The placenta as an important source of vitamin D regulates its metabolism through the vitamin D receptor (VDR), but the mechanism by which VDR regulates trophoblast function is poorly understood. Our study aimed at determining placental VDR expression in FGR and gestation-matched control (GMC) pregnancies and identifying the actions of VDR in trophoblast differentiation and apoptosis. Placentae were collected from a well-defined cohort of idiopathic FGR and GMC pregnancies. VDR mRNA and protein expressions were determined by PCR, immunohistochemistry and immunoblotting, while functional consequences of VDR inactivation in vitro were determined on BeWo cells by determining changes in differentiation, attachment and apoptosis. Significant decreases in VDR mRNA expression (p = 0.0005) and protein expression (p = 0.0003) were observed in the FGR samples, while VDR inactivation, which showed markers for differentiation, cell attachment and apoptosis, was significantly increased. Thus, decreased placental VDR may contribute to uncontrolled premature differentiation and apoptosis of trophoblasts that are characteristics of idiopathic FGR pregnancies.
  
  
  CONCLUSIONS
  Fetal growth restriction (FGR) affects up to 5 % of all pregnancies worldwide. FGR is the second highest cause of perinatal mortality and morbidity. The placenta plays a pivotal role in vitamin D metabolism during pregnancy. Vitamin D deficiency is associated with adverse pregnancy outcomes. Placental vitamin D receptor expression is decreased in FGR.
authors.affiliation: Department of Perinatal Medicine Pregnancy Research Centre, The University of Melbourne, Melbourne, Australia.
authors.forename: T P H
authors.initials: TP
authors.lastname: Nguyen
authors.forename: H E J
authors.initials: HE
authors.lastname: Yong
authors.forename: T
authors.initials: T
authors.lastname: Chollangi
authors.forename: A J
authors.initials: AJ
authors.lastname: Borg
authors.forename: S P
authors.initials: SP
authors.lastname: Brennecke
authors.forename: P
authors.initials: P
authors.lastname: Murthi
mesh_terms: D017209:Apoptosis; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D047109:Fetal Development / Q000235:genetics / Q000502:physiology*; D005317:Fetal Growth Retardation / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male; D010920:Placenta / Q000503:physiopathology*; D011247:Pregnancy; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D018167:Receptors, Calcitriol / Q000096:biosynthesis* / Q000235:genetics; D014327:Trophoblasts / Q000166:cytology; D014807:Vitamin D / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018167:Receptors, Calcitriol; D014807:Vitamin D