A novel update on vitamin D in recurrent pregnancy loss (Review)

Abstract

Recurrent pregnancy loss (RPL) is usually characterized as ≥3 miscarriages before 20 weeks of gestation. Patients with RPL may have autoimmune abnormalities or alloimmune problems. Vitamin D has a major function on the mechanism of immunomodulation at the maternal‑fetal interface. However, whether vitamin D can be used as an effective method to treat patients with RPL requires investigation. It has been reported that vitamin D could prevent the occurrence of antiphospholipid syndrome (APS) by reducing the expression levels of anti‑β2 glycoprotein and tissue factor in RPL cases with APS. In addition, there is an opposite relationship between vitamin D and thyroid peroxidase antibody levels in autoimmune thyroid disease cases with RPL. Vitamin D changes the ratio of T helper (Th) 1/Th2 and regulatory T cell/Th17 to a certain extent, as well as affects the activity of natural killer cells and the production of cytokines to reduce the incidence of RPL. The objective of the current review was to address the research progress of vitamin D in RPL in recent years, which could facilitate the use of vitamin D treatment to enhance the pregnancy outcome of RPL. Collectively, it was suggested that vitamin D may be used as an important and effective immunotherapeutic agent for patients with RPL.

Keywords: vitamin D; RPL; autoimmunity; cellular immunity; NK cells.

Figure 1.

Immune impact of vitamin D on RPL. Vitamin D suppresses cytokines produced by Th1 cells and promotes cytokines secreted by Th2 cells. Moreover, vitamin D increases the function of Treg cells, whereas it reduces the number of Th17 cells, which secrete IL-17. Vitamin D is negatively correlated with IL-23, while IL-23 is positively associated with IL-17. Peripheral NK cell activation and its cytotoxic actions are inhibited by vitamin D. Vitamin D inhibits peripheral NK cytotoxicity by suppressing IFN-γ and IL-2. VEGF and G-CSF production are stimulated by vitamin D. Vitamin D promotes the proliferation of the complement inhibitor CD55 and inhibits anti-β2 glycoprotein. By inhibiting TF and APAs, vitamin D can prevent the occurrence of APS in RPL. RPL, recurrent pregnant loss; G-CSF, granulocyte colony-stimulating factor; TF, tissue factor; APS, antiphospholipid syndrome; APAs, antiphospholipid antibodies; Treg, regulatory T; Th, T helper; NK, natural killer.