Interleukin-1 beta induced lewis X alteration in unexplained recurrent miscarriage
JOURNAL OF REPRODUCTIVE IMMUNOLOGY(2023)
Abstract
Interleukin-1 beta (IL-1β) exhibits significant functions during implantation and placenta development, while increased level of IL-1β was observed in the endometrium as well as decidua of unexplained recurrent miscarriage (uRM) patients. Lewis X (LeX) is one of the commonest carbohydrate cell adhesion molecules that play pivotal roles in human embryogenesis and cell-cell interactions, it is also abundant at the endometrium during implantation stage. IL-1β has been reported to facilitate the upregulation of lewis antigens in many types of cancer cells. Currently there is no reports related to LeX expression in the decidua of uRM patients, and its potential linkage with aberrantly elevated IL-1β in the pathogenesis of uRM remains enigmatic. Paraffin-embedded slides originating from placental tissue were collected from patients experiencing a miscarriage early in their pregnancy (6–13 weeks). Tissues collected from recurrent (RM, n = 15) miscarriages and legally terminated normal pregnancies (NC, n = 10), considered as control group, were analyzed using immunohistochemical (IHC) staining. The expression of LeX and potentially associated glycosyltransferase genes FUT1/3/4 and ST3GAL3/4/6 in RL95-2 cells in response to IL-1β treatment were measured by flow cytometry, immunocytochemical staining, and real-time quantitative polymerase chain reaction (RT-qPCR). IHC staining revealed that LeX was mainly expressed in the luminal and glandular epithelium, FUTs and ST3GALs located in both stromal and epithelial cells. Expression of LeX, FUT3/4, and ST3GAL3/4 were significantly upregulated in RM group, while FUT1 was downregulated. ST3GAL6 showed no significant differences between groups. Treatment of RL95-2 cells with IL-1β induced significantly increased the expression of LeX. The transcript level of glycosyltransferase gene FUT3 was significantly elevated and that of FUT4 and ST3GAL3/4 were slightly suppressed by the treatment. LeX and pertinent glycosyltransferase genes FUT1/3/4 and ST3GAL3/4 are notably dysregulated in the decidua of uRM patients. Aberrantly elevated IL-1β in uRM may facilitate the inappropriate implantation through enhancing the expression of LeX and FUT3.
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Key words
unexplained recurrent miscarriage
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