Altered decidual and placental catabolism of vitamin D may contribute to the aetiology of spontaneous miscarriage.

INTRODUCTION:Vitamin D catabolizing enzymes, along with vitamin D receptor (VDR) and vitamin D binding protein (DBP) are expressed in the decidua and placenta during pregnancy and capable of synthesizing active vitamin D. Vitamin D plays roles in immunoregulation and trophoblast invasion, key features of a successful pregnancy. Epidemiological data suggests that vitamin D deficiency is associated with both spontaneous and recurrent miscarriage but few studies have investigated the expression of the key vitamin D catabolizing enzymes in miscarriage. METHODS:Placenta and decidua were collected after termination of apparently normal pregnancies (controls, n = 22) or spontaneous miscarriage (n = 20). Immunohistochemical staining, and qRT-PCR were performed for CYP27B1, CYP24A1, CYP2R1, VDR and DBP (not qRT-PCR). HTR-8/SVneo cells were cultured in CoCL₂ (hypoxic mimetic) or LPS (bacterial infection mimetic) for 24 h, RNA extracted and qRT-PCR performed for CYP27B1, CYP24A1, CYP2R1 and VDR. RESULTS:In spontaneous miscarriage, placental and decidual expression of CYP27B1 was reduced, while expression of CYP24A1, VDR and DBP was increased. When a trophoblast cell line was treated with CoCL₂ expression of CYP27B1 was increased and CYP24A1 was reduced, while LPS induced expression of VDR. DISCUSSION:This is the first report of altered utero-placental vitamin D catabolism in spontaneous miscarriage. It is becoming accepted that women who are undergoing assisted reproductive technologies should ensure they have sufficient vitamin D levels prior to pregnancy, these data support that all women should ensure they are vitamin D replete before planning to get pregnant.

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