Vitamin D Effects on the Immune System from Periconception through Pregnancy

Abstract

Vitamin D is a well-known secosteroid and guardian of bone health and calcium homeostasis. Studies on its role in immunomodulatory functions have expanded its field in recent years. In addition to its impact on human physiology, vitamin D influences the differentiation and proliferation of immune system modulators, interleukin expression and antimicrobial responses. Furthermore, it has been shown that vitamin D is synthesized in female reproductive tissues and, by modulating the immune system, affects the periconception period and reproductive outcomes. B cells, T cells, macrophages and dendritic cells can all synthesize active vitamin D and are involved in processes which occur from fertilization, implantation and maintenance of pregnancy. Components of vitamin D synthesis are expressed in the ovary, decidua, endometrium and placenta. An inadequate vitamin D level has been associated with recurrent implantation failure and pregnancy loss and is associated with pregnancy-related disorders like preeclampsia. This paper reviews the most important data on immunomodulatory vitamin D effects in relation to the immune system from periconception to pregnancy and provides an insight into the possible consequences of vitamin D deficiency before and during pregnancy.

Keywords: assisted reproduction; immune system; preeclampsia; pregnancy; recurrent pregnancy loss; reproductive tissue; vitamin D; vitamin D deficiency.

Figure 1

Vitamin D effects on immune cells and cells of the reproductive tract. Vitamin D precursors are ingested through food or supplements and further metabolized in the body to the active hormone, which exerts different responses of mediators of the immune system. Vitamin D affects maturation, differentiation, interleukin expression and immunomodulatory functions of immune cells like B cells, T cells, Th (helper) cells, Treg (regulatory) cells, macrophages (M-phage) and dendritic cells. The expression of immunoactive cytokines by cells of the reproductive tract like trophoblasts is modulated by vitamin D. Vitamin D regulates hormone (e.g. progesterone, AMH and androstenedione) and FSH and AMH receptor expression in theca and granulosa cells [4]. ESC; endometrial stem cells; uNK uterine natural killer cells; DC dendritic cell, M-Phage macrophage; Th T helper; CAMP cathelicidin, antimicrobial peptide; WEC whole endometrium cells; AMH anti mullerian hormone; FSH follicle stimulating hormone.

Figure 2

Components of vitamin D synthesis in female reproductive tissues and cells of the immune system. (A) Vitamin D exerts immunomodulatory effects with impact on reproductive tissues from the periconception period throughout pregnancy. (B) Components of the vitamin D metabolic system are expressed in female reproductive tissues, including ovary, decidua, endometrium and placenta and multiple immune cells. Proposed immunomodulatory effects of vitamin D include the improvement of immune balance, tolerance and maintenance of pregnancy trough effects on B cells, T cells, macrophages and dendritic cells. +; expression known, n.a.; not available.