Expression of interleukin-22 in decidua of patients with early pregnancy and unexplained recurrent pregnancy loss

Abstract

Purpose Researchers have hypothesized that an imbalance of immune cells in the uterine decidua and a dysfunction in cytokines they produce may contribute to recurrent pregnancy loss (RPL). The objective of this study was to determine if IL-22, IL-23 and IL-17 are expressed abnormally in the decidua of patients with RPL compared to those women with a normal pregnancy. We also sought to confirm that uterine natural killer (uNK) cells are lower in the decidua of patients with RPL, as well as identify IL-22 expression by uNK cells. Methods After meeting strict inclusion criteria, maternal decidua of nine patients with unexplained RPL and a confirmed euploid fetal loss, and 11 gestational age-matched patients undergoing elective pregnancy termination were included in our analysis. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to quantify RNA expression, Western blot was performed to quantify protein expression and immunohistochemistry (IHC) was performed to identify IL-22 and uNK cells. Results We found that women with unexplained RPL and a euploid fetal loss had significantly less gene and protein expression of IL-22 in the decidua. Additionally, we found that IL-22 is primarily expressed by uNK cells in the decidua. Conclusions In conclusion, our results suggest that lower levels of IL-22 in the uterine decidua in patients with unexplained RPL may contribute to a disruption of decidual homeostasis and ultimately lead to early pregnancy loss.

VEGF may contribute to macrophage recruitment and M2 polarization in the decidua

“…Tissue samples were collected after obtaining informed consent under protocols approved by the Wayne State University and Stanford University IRBs on the use of Human Subjects in Medical Research for our previous studies [ 22 , 30 , 31 ]. Briefly, secretory phase endometrium was obtained from subjects undergoing hysterectomy for benign indications, such as fibroids or chronic pelvic pain, in the age group between 28 and 39 years during the secretory phase of the cycle, as described previously [ 31 ].…”

“…Full-thickness endometrial OCT blocks (2–3 mm) and cryosections (10μm) were prepared for in situ hybridization studies and RNA extracted for qPCR analysis as described below (n = 5). Decidual samples from early pregnancy (5–9 weeks) were collected from subjects undergoing elective termination of pregnancy following the same procedures as described previously [ 30 , 32 ]. After dilation and curettage, deciduas were separated from chorionic villi and other fetal tissues under a dissecting microscope and processed for RNA extraction and preparation of OCT blocks.…”

Endometrial Immune Dysfunction in Recurrent Pregnancy Loss

“…An increase in the proportion of NK22 cells has been detected in the endometrium, as well as in the peripheral blood, of women with unexplained RPL compared with women with unexplained infertility [136,137]. However, uNK cells in the decidua of women with unexplained RPL have a significantly lesser gene and protein expression of IL-22 than normal women [138]. Further investigation is needed to fully clarify the role of endometrial IL-22 and NK22 in RPL.…”

Are neutrophil to lymphocyte ratio and platelet to lymphocyte ratio clinically useful for the prediction of early pregnancy loss?

“…In several studies, it was reported that the cytokine levels are different in women with recurrent miscarriages. In the study of O'Hern Perfetto et al [12], it was suggested that the lower levels of IL-22 in the uterine decidua in patients with unexplained recurrent pregnancy loss. However, there are conflicting results in the literature about the status of the systemic inflammatory response in spontaneous miscarriage.…”