Women with recurrent spontaneous abortion have decreased 25(OH) vitamin D and VDR at the fetal-maternal interface

Abstract

Immunological mechanisms have been proposed to underlie the pathogenesis of recurrent spontaneous abortion (RSA). Vitamin D has a potent immunomodulatory effect, which may affect pregnancy outcome. The objective of this study was to investigate 25-hydroxyvitamin D [25(OH) D] concentration and vitamin D receptor (VDR) expression in the decidual tissues of RSA patients. Thirty women with RSA (RSA group) and thirty women undergoing elective abortion (control group) were recruited during 2016 from gynecology outpatient clinics. We measured 25(OH) D, interleukin (IL)-17, IL-23, transforming growth factor β (TGF-β), VDR and 1-α-hydroxylase (CYP27B1) in decidual tissues collected during the abortion procedure. In the RSA group, 25(OH) D and TGF-β were significantly decreased while IL-17 and IL-23 were significantly increased compared with the control group. VDR expression was significantly decreased in the RSA group compared with the control group. Logistic regression analysis showed a significant negative correlation between 25(OH) D in decidual tissues and RSA. These results indicated that vitamin D concentrations in the decidua are associated with inflammatory cytokine production, suggesting that vitamin D and VDR may play a role in the etiology of RSA.

Recurrent pregnancy loss and vitamin D: A review of the literature

“…44,67,68 The role of VD in reproductive health is corroborated by the presence of VDR and enzymes which participate in VD metabolism in endometrium and decidua. 40,[80][81][82] The studies suggest that VD might play an immunoregulatory role, promoting implantation and a successful pregnancy. Furthermore, women with RPL seem to have more auto and cellular immune abnormalities especially if they have low VD levels.…”

“…Furthermore, studies about VD levels, expression and function of VDR and other molecules which participate in VD metabolism in fetal-maternal interface are limited, some of them had different results and used small samples. [78][79][80][81] In addition, the 11 studies included in this review were conducted in USA, 67,73 Iran, 75,[77][78][79] China, 68,[80][81][82] and Egypt, 76 countries where food intake patterns, UV exposure, skin color, latitude, and other factors that affect VD levels are probably different from Europe, Mediterranean, or Portugal.…”

“…,73 Iran,75,[77][78][79] China,68,[80][81][82] and Egypt,76 countries where food intake patterns, UV exposure, skin color, latitude, and other factors that affect VD levels are probably different from Europe, Mediterranean, or Portugal.Of note, VD is not the only immunomodulatory agent reported in RPL. Intravenous immunoglobulin (IVIG) seems to act through a multitude of mechanisms that include reducing the activity of NK cells, increasing the activity of suppressor T cells, elimination of immune complexes, down-regulation of stimulatory receptors, and upregulation of inhibitory receptors on the surface of different immune cells 85,86.…”

Placental endovascular extravillous trophoblasts (enEVTs) educate maternal T‐cell differentiation along the maternal‐placental circulation

“…In parallel, the portions of FOXP3 + Tregs in remodelled SPA and IVS are substantially reduced compared with the healthy pregnant controls (Figure 6B). Significant decline of Treg amount in RSA decidua and peripheral blood, as well as the diminishment of circulating TGF‐β1 and IL‐2 in RSA patients, has been demonstrated in many other studies 19‐21,26‐28 . Thus, it is possible that the insufficient immune tolerance in RSA pregnancy may, at least in part, result from the dysregulation of functional enEVT differentiation.…”

“…Transforming growth factor‐beta1 (TGF‐β1) is a key factor that triggers the differentiation of the inducible Tregs through induction of transcription factor FOXP3 23,24 . In parallel with the change in Treg proportion, peripheral TGF‐β1 level is higher in pregnant women compared with the non‐pregnant individuals, 25 and its expression is sharply reduced in the peripheral blood and decidua of RSA patients 26‐29 . It is most likely that TGF‐β1‐regulated differentiation of Tregs critically participates in maintaining a healthy pregnancy.…”