Endometrial TGF-β, IL-10, IL-17 and autophagy are dysregulated in women with recurrent implantation failure with chronic endometritis

Abstract

Background: Chronic endometritis (CE) is a condition which results in reduced receptivity of embryos by dysregulated lymphocyte subsets, abnormal expression of cytokines, chemokines and other regulatory molecules in the endometrium (EM). Macroautophagy (autophagy), the highly conserved cellular homeostasis pathway, plays an essential role in the development and function of T lymphocytes, and supports T cell lineage stability and survival fitness. The possible relationships between autophagy and local cytokine milieus in repeated implantation failure (RIF) with CE have not been elucidated yet. Methods: This case-control study was performed at a large reproductive medicine center between February 2015 and July 2016. Seventy-five recurrent implantation falliure women with CE who had "strawberry aspect" and 75 women with male factor infertility were included. In this study, endometrial expressions of IL-17, IL-10, TGF-β and autophagy related molecules, including LC3-II and mTORC1 were investigated by qRT-PCR, Western blot, immunofluorescence and immunohistochemistry assays. Results: The expression of IL-17 was significantly higher in patients with CE compared to women with male factor infertility, while the expressions of IL-10 and TGF-β were significantly lower. Moreover, the expression of autophagy (LC3-II) is increased, while the expression of mTORC1 was impaired. Conclusions: CE is associated with shifted cytokine milieu towards Th17 over Treg immunity in endometrium through impaired autophagy by decreased mTORC1.