title: Women with Recurrent Miscarriage Have Decreased Expression of 25-Hydroxyvitamin D3-1α-Hydroxylase by the Fetal-Maternal Interface.
abstract: BACKGROUND
  Effects of vitamin D deficiency in pregnancy have been associated with some adverse pregnancy outcomes. The 25-hydroxyvitamin D3-1α-hydroxylase (CYP27B1) is integral to the vitamin D metabolic pathway. The enzyme catalyzes localized conversion of pro-hormone 25-hydroxyvitamin D3 to active 1,25-dihydroxyvitamin D3. Our aim was to investigate the expression of CYP27B1 at the fetal-maternal interface in the first trimester pregnancy and to determine whether CYP27B1 was associated with recurrent miscarriage (RM).
  
  
  METHODS
  Expressions of CYP27B1 mRNA and protein in villi and decidua from 20 women undergoing primary miscarriage, 20 women with RM and 20 women with normal pregnancy were evaluated by western blot, and quantitative real-time PCR. The co-localization of CYP27B1 and certain cytokines including IL-10, IFN-γ, TNF-α, and IL-2 expression were examined using immunohistochemistry and confocal microscopy.
  
  
  RESULTS
  Women with RM had a significantly lower expression of CYP27B1 mRNA and protein in villous and decidual tissues compared with the normal pregnant women (P = 0.000 in villus, P = 0.002 in decidua for mRNA; P = 0.036 in villus, P = 0.007 in decidua for protein.). Compared with the normal pregnancy, immunostaining for CYP27B1 was significantly decreased in villous trophoblasts and decidual glandular epithelial cells in RM women. No significant differences in the localization of CYP27B1, IL-10, IFN-γ, TNF-α, and IL-2 expression were identified between the normal pregnant and RM women.
  
  
  CONCLUSIONS
  Women with RM have a lower level of CYP27B1 expression in chorionic villi and decidua compared with normal pregnant women, suggesting that reduced CYP27B1 expression may be associated with RM. The consistent localization of CYP27B1 and IL-10, IFN-γ, TNF-α, and IL-2 expression in villous and decidual tissues suggests the importance of the local production of 1,25(OH)2D3 at the fetal-maternal interface to regulate cytokine responses.
authors.affiliation: Department of Obstetrics and Gynecology in First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.|Nursing Department in Xi'an Medical College, Xi'an, China.
authors.forename: Li-Qin
authors.initials: LQ
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology in First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Xiao-Ting
authors.initials: XT
authors.lastname: Yan
authors.affiliation: Reproductive Center in Fourth Hospital of Xi'an, Xi'an, China.
authors.forename: Chun-Fang
authors.initials: CF
authors.lastname: Yan
authors.affiliation: Department of Obstetrics and Gynecology in First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.|Reproductive Center in Fourth Hospital of Xi'an, Xi'an, China.
authors.forename: Xin-Wen
authors.initials: XW
authors.lastname: Zhang
authors.affiliation: Laboratory Department in First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Ling-Yun
authors.initials: LY
authors.lastname: Hui
authors.affiliation: Clinical Sciences Research Lab, Translational Medicine Section, Division of Biomedical Sciences, Warwick Medical School, University of Warwick, University Hospital, Coventry, United Kingdom.
authors.forename: Mingzhan
authors.initials: M
authors.lastname: Xue
authors.affiliation: Department of Obstetrics and Gynecology in First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Xue-Wen
authors.initials: XW
authors.lastname: Yu
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000026:Abortion, Habitual / Q000473:pathology*; D000328:Adult; D002117:Calcitriol / Q000096:biosynthesis; D002824:Chorionic Villi / Q000378:metabolism*; D003656:Decidua / Q000378:metabolism*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014592:Uterine Hemorrhage / Q000473:pathology*; D014808:Vitamin D Deficiency / Q000473:pathology
chemical_list: C508609:IL10 protein, human; C508594:IL2 protein, human; D007376:Interleukin-2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; C000600378:CYP27B1 protein, human; D002117:Calcitriol