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(American Journal of Pathology. 2002;161:105-114.)
© 2002 American Society for Investigative Pathology

Regular Articles

The Ontogeny of 25-Hydroxyvitamin D₃ 1-Hydroxylase Expression in Human Placenta and Decidua

Daniel Zehnder^*, Katie N. Evans^*, Mark D. Kilby, Judith N. Bulmer, Barbara A. Innes, Paul M. Stewart^* and Martin Hewison^*

From the Division of Medical Sciences,^*The University of Birmingham, Queen Elizabeth Hospital, Birmingham; the Division of Reproductive and Child Health,The University of Birmingham, Birmingham Women’s Hospital, Birmingham; and the Department of Pathology,University of Newcastle upon Tyne, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom

In addition to its classical calciotropic effects, the active form of vitamin D, 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) is a potent anti-proliferative/immunomodulatory secosteroid. The enzyme that catalyzes the synthesis of 1,25(OH)₂D₃, 1-hydroxylase (1-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 1-OHase expression in human placenta and decidua. Protein for 1-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 1-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). 1-OHase expression in decidua was 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, 1-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)₂D₃ (vitamin D receptor) indicated that, as with 1-OHase, highest levels of expression occurred in first trimester decidua. However, changes in vitamin D receptor mRNA expression across gestation were less pronounced than 1-OHase. These spatiotemporal data emphasize the potential importance of 1-OHase during early fetoplacental life and, in particular, suggest an autocrine/paracrine immunomodulatory function for the enzyme.

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