Regulatory T cells, inflammation, and endoplasmic reticulum stress in women with defective endometrial receptivity

Objective To investigate immunologic parameters and endoplasmic reticulum (ER) stress associated with unexplained infertility. Design Case-control study. Setting Academic center. Patient(s) Women with no fertility problems (FS) (n = 13), women with recurrent miscarriage (RM) (n = 15) and women with repeated in vitro fertilization failure (RIF) (n = 15). Intervention(s) Endometrial biopsy and collection of peripheral blood during the midsecretory phase of menstrual cycle. Main Outcome Measure(s) Leptin, resistin, soluble tumor necrosis factor receptor (sTNF-R), myeloperoxidase (MPO), soluble intercellular adhesion molecule 1 (sICAM-1), and interleukin 22 (IL-22) concentration in peripheral blood, endometrial CD3+, CD4+, CD5+, CD8+, and FoxP3+ T lymphocytes, and endometrial expression of HSPA5, a specific marker of ER stress. Result(s) We found an increase of proinflammatory molecules such as resistin, leptin, and IL-22 in both RM and RIF patients; sTNF-R and MPO only in RIF patients when compared with the FS women. We also found in endometria of infertile women a statistically significant increase of CD3+, CD4+, CD8+ in both RM and RIF patients and CD5+ in RM patients when compared with FS women. This was paralleled by a statistically significant reduction of infiltrating FoxP3+ regulatory T cells. Finally, endometrial HSPA5 expression levels were statistically significantly up-regulated in both RM and RIF patients. Conclusion(s) Women with RM and RIF showed an increase of circulating proinflammatory cytokines, altered endometrial T lymphocytes subsets, and signs of endometrial ER stress.