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Fertil Steril. 2015 Jun;103(6):1579-86.e1. doi: 10.1016/j.fertnstert.2015.03.014. Epub 2015 Apr 29.

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

Author information

1
Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore" CNR, Naples, Italy.
2
Dipartimento di Scienze Biomediche Avanzate, Università "Federico II," Naples, Italy.
3
Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, Università "Federico II," Naples, Italy.
4
Dipartimento di Scienze Mediche Traslazionali and Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore" CNR, Università "Federico II," Naples, Italy.
5
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università "Federico II," Naples, Italy.
6
Dipartimento di Medicina e Chirurgia, Università di Salerno, Baronissi Campus, Salerno, Italy; IRCCS Multimedica, Milan, Italy.
7
Dipartimento di Scienze Mediche Traslazionali and Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore" CNR, Università "Federico II," Naples, Italy. Electronic address: lulianic@unina.it.

Abstract

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.

KEYWORDS:

Endometrial receptivity; endoplasmic reticulum stress; proinflammatory cytokines; regulatory T cells

[Indexed for MEDLINE]

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