title: The ontogeny of 25-hydroxyvitamin D(3) 1alpha-hydroxylase expression in human placenta and decidua.
abstract: In addition to its classical calciotropic effects, the active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is a potent anti-proliferative/immunomodulatory secosteroid. The enzyme that catalyzes the synthesis of 1,25(OH)(2)D(3), 1alpha-hydroxylase (1alpha-OHase), is expressed in many human tissues, highlighting its possible role as an autocrine/paracrine activator of vitamin D. Immunohistochemical and RNA analyses were used to characterize the ontogeny of 1alpha-OHase expression in human placenta and decidua. Protein for 1alpha-OHase was detectable in trophoblast and decidua; the latter being stronger in decidualized stromal cells than macrophages, with no staining of lymphocytes. Quantitative reverse transcriptase-polymerase chain reaction was used to assess changes in mRNA expression for 1alpha-OHase at different gestations: first (mean, 9.1 +/- 1.5 weeks); second (mean, 14 +/- 1.8 weeks), and third trimester (mean, 39.3 +/- 2.5 weeks). 1alpha-OHase expression in decidua was approximately 1000-fold higher in first (95% confidence limits, 611 to 1376) and second (95% confidence limits, 633 to 1623) trimester biopsies when compared with the third trimester (95% confidence limits, 0.36 to 2.81) (both P < 0.001). In placenta, 1alpha-OHase expression was 80-fold higher in the first (range, 42 to 137) and second (range, 30 to 199) trimester when compared with third trimester biopsies (0.6 to 1.6) (both P < 0.001). Similar results were obtained by semiquantitative IHC. Parallel analysis of the receptor for 1,25(OH)(2)D(3) (vitamin D receptor) indicated that, as with 1alpha-OHase, highest levels of expression occurred in first trimester decidua. However, changes in vitamin D receptor mRNA expression across gestation were less pronounced than 1alpha-OHase. These spatiotemporal data emphasize the potential importance of 1alpha-OHase during early fetoplacental life and, in particular, suggest an autocrine/paracrine immunomodulatory function for the enzyme.
authors.affiliation: Division of Medical Sciences, The University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zehnder
authors.forename: Katie N
authors.initials: KN
authors.lastname: Evans
authors.forename: Mark D
authors.initials: MD
authors.lastname: Kilby
authors.forename: Judith N
authors.initials: JN
authors.lastname: Bulmer
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Innes
authors.forename: Paul M
authors.initials: PM
authors.lastname: Stewart
authors.forename: Martin
authors.initials: M
authors.lastname: Hewison
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D003656:Decidua / Q000166:cytology / Q000201:enzymology*; D005260:Female; D006801:Humans; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D012333:RNA, Messenger / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D012333:RNA, Messenger; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase