Differences in Cytokine Expression and STAT3 Activation between Healthy Controls and Patients of Unexplained Recurrent Spontaneous Abortion (URSA) during Early Pregnancy

Abstract

Unexplained recurrent spontaneous abortion (URSA) is a common complication of pregnancy. Although tolerance of the maternal immune system is considered to be essential for a normal pregnancy, the precise mechanism underlying the pathogenesis of URSA remains to be fully elucidated, albeit it is known to involve inflammation. Here, we examine the relationship between the expression of inflammatory cytokines and the activation of downstream signaling pathways in URSA patients. Decidual and peripheral blood samples were collected from 30 URSA patients and from 30 women with normal early pregnancies. Western blot analysis was used to measure the expression levels of signal transducers and activators of transcription 3(STAT3), phosphorylated STAT3(p-STAT3), and interleukin-17 receptor(IL-17R) in the decidual samples. Enzyme-linked immunosorbent assay was used to assess the levels of IL-17, IL-10, IL-6, and IL-23 in the peripheral blood and decidual samples. In the URSA patients, the IL-10 expression levels were lower than those in the control subjects (P<0.05), whereas IL-6, IL-17, and IL-23 were all expressed at higher levels(P<0.05). Furthermore, the expression levels of IL-17R and p-STAT3 were higher in the URSA patients, exhibiting a trend similar to that of IL-23. Our finding of increased IL-23 expression in the deciduae and peripheral blood of patients with URSA suggest that this maybe a contributing factor to the pathogenesis of this disease. Likewise, STAT3 activation through its phosphorylation, which was associated with the IL-23 increase, may also be involved in URSA pathogenesis. However, the precise pathogenic mechanism requires further study.

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

“…Th17 cells and promotes the secretion of IL-17. The increased expression of IL-23 and IL-17 in women with RPL was reported in previous studies 83. In this study, RPL was significantly negatively correlated with 25(OH)D, suggesting that low VD levels in decidual tissues were associated with RPL and VD might play a vital role in influencing the IL-23/IL-17 axis.…”

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

“…Interleukin-23 (IL-23) can promote Th17 cell differentiation and maintain the Th17 response. In a previous study, we found increased IL-17 and IL-23 expression in women with RSA ( 16 ). Therefore, it is becoming clear that immune disturbances are involved in the pathogenesis of RSA ( 17 ).…”

“…Western blotting was used to measure the expression of VDR and CYP27B1 in decidual tissues following a previously described method ( 16 ). Briefly, total protein was isolated from each decidual tissue sample and mixed with 5× sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) loading buffer (Baomanbi, China) at 4:1 v/v.…”

Prednisone may rebuild the immunologic homeostasis: Alteration of Th17 and Treg cells in the lymphocytes from rats' spleens after treated with prednisone‐containing serum

“…In inflammatory bowel disease mice, there was a reduction of CD4 + T cells producing IFN‐γ, an increased frequency of the putative regulatory population of T cells producing IL‐10, and an increment in the frequency of the regulatory markers GITR, CTLA‐4, PD‐1, CD73, and FoxP3, after treating with glucocorticoid (Sales‐Campos et al, ). We have found that the serum concentration of IL‐10 in patients with URSA is much lower than that in healthy controls, whereas the expression of IL‐17 is at a higher level (Cai, Li, Huang, Fu, & Wu, ). It was reported by a recent study that the patients with URSA who received immunotherapy got an increment of Treg cells and an reduction of IL‐2 level.…”