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

We discuss a series of immunologic alterations are associated with endoplasmic reticulum stress during the window of implantation in the endometrium of infertile women.


Mario Galgani, Ph.D., Luigi Insabato, M.D., Gaetano Cal├Č, Ph.D., Anna Nunzia Della Gatta, M.D., Paola Mirra, Ph.D., Federica Papaccio, B.Sc., Marianna Santopaolo, B.Sc., Carlo Alviggi, M.D., Antonio Mollo, M.D., Ida Strina, M.D., Giuseppe Matarese, M.D., Francesco Beguinot, M.D., Giuseppe De Placido, M.D., Luca Ulianich, Ph.D.

Volume 103, Issue 6, Pages 1579-1586



To investigate immunologic parameters and endoplasmic reticulum (ER) stress associated with unexplained infertility.


Case-control study.


Academic center.


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).


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.


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.


Women with RM and RIF showed an increase of circulating proinflammatory cytokines, altered endometrial T lymphocytes subsets, and signs of endometrial ER stress.

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