title: Expressions of vitamin D metabolic components VDBP, CYP2R1, CYP27B1, CYP24A1, and VDR in placentas from normal and preeclamptic pregnancies.
abstract: Vitamin D insufficiency/deficiency during pregnancy has been linked to increased risk of preeclampsia. Placenta dysfunction plays an important role in the pathogenesis of this pregnancy disorder. In this study, we tested the hypothesis that disturbed vitamin D metabolism takes place in preeclamptic placentas. Protein expressions of vitamin D binding protein (VDBP), 25-hydroxylase (CYP2R1), 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1), and vitamin D receptor (VDR) were examined in placentas from normotensive and preeclamptic pregnancies. By immunostaining we found that in normal placenta VDBP, CYP24A1, and VDR expressions are localized mainly in trophoblasts, whereas CYP2R1 and CYP27B1 expressions are localized mainly in villous core fetal vessel endothelium. Protein expressions of CYP2R1 and VDR are reduced, but CYP27B1 and CYP24A1 expressions are elevated, in preeclamptic compared with normotensive placentas. Because increased oxidative stress is an underlying pathophysiology in placental trophoblasts in preeclampsia, we further determined whether oxidative stress contributes to altered vitamin D metabolic system in placental trophoblasts. Trophoblasts isolated from normal-term placentas were treated with hypoxic-inducing agent CoCl(2), and protein expressions of VDBP, CYP2R1, CYP27B1, CYP24A1, and VDR were determined. We found that hypoxia-induced downregulation of VDBP, CYP2R1, and VDR and upregulation of CYP27B1 and CYP24A1 expressions were consistent with that seen in preeclamptic placentas. CuZnSOD expression was also downregulated in trophoblasts treated with CoCl(2). These results provide direct evidence of disrupted vitamin D metabolic homeostasis in the preeclamptic placenta and suggest that increased oxidative stress could be a causative factor of altered vitamin D metabolism in preeclamptic placentas.
authors.affiliation: Dept. of Obstetrics and Gynecology, LSUHSC-Shreveport, P. O. Box 33932, Shreveport, LA 71130, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Ma
authors.forename: Yang
authors.initials: Y
authors.lastname: Gu
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.forename: Jingxia
authors.initials: J
authors.lastname: Sun
authors.forename: Lynn J
authors.initials: LJ
authors.lastname: Groome
authors.forename: Yuping
authors.initials: Y
authors.lastname: Wang
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000096:biosynthesis*; D000293:Adolescent; D000328:Adult; D053493:Cholestanetriol 26-Monooxygenase / Q000096:biosynthesis*; D003035:Cobalt / Q000633:toxicity; D000072467:Cytochrome P450 Family 2; D005260:Female; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010920:Placenta / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D018167:Receptors, Calcitriol / Q000096:biosynthesis*; D013250:Steroid Hydroxylases / Q000096:biosynthesis*; D013482:Superoxide Dismutase / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism*; D014809:Vitamin D-Binding Protein / Q000096:biosynthesis*; D065668:Vitamin D3 24-Hydroxylase; D055815:Young Adult
chemical_list: D018167:Receptors, Calcitriol; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; D003035:Cobalt; D013250:Steroid Hydroxylases; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D013482:Superoxide Dismutase; C018021:cobaltous chloride