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.


METHODS
Case-control study.


METHODS
Academic center.


METHODS
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).


METHODS
Endometrial biopsy and collection of peripheral blood during the midsecretory phase of menstrual cycle.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Women with RM and RIF showed an increase of circulating proinflammatory cytokines, altered endometrial T lymphocytes subsets, and signs of endometrial ER stress.
Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore" CNR, Naples, Italy.
Mario
M
Galgani
Dipartimento di Scienze Biomediche Avanzate, Università "Federico II," Naples, Italy.
Luigi
L
Insabato
Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore" CNR, Naples, Italy.
Gaetano
G
Calì
Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, Università "Federico II," Naples, Italy.
Anna Nunzia
AN
Della Gatta
Dipartimento di Scienze Mediche Traslazionali and Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore" CNR, Università "Federico II," Naples, Italy.
Paola
P
Mirra
Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore" CNR, Naples, Italy.
Federica
F
Papaccio
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università "Federico II," Naples, Italy.
Marianna
M
Santopaolo
Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, Università "Federico II," Naples, Italy.
Carlo
C
Alviggi
Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, Università "Federico II," Naples, Italy.
Antonio
A
Mollo
Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, Università "Federico II," Naples, Italy.
Ida
I
Strina
Dipartimento di Medicina e Chirurgia, Università di Salerno, Baronissi Campus, Salerno, Italy; IRCCS Multimedica, Milan, Italy.
Giuseppe
G
Matarese
Dipartimento di Scienze Mediche Traslazionali and Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore" CNR, Università "Federico II," Naples, Italy.
Francesco
F
Beguinot
Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, Università "Federico II," Naples, Italy.
Giuseppe
G
De Placido
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.
Luca
L
Ulianich
D000328:Adult; D016022:Case-Control Studies; D010064:Embryo Implantation / Q000276:immunology*; D004721:Endoplasmic Reticulum / Q000276:immunology* / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000276:immunology* / Q000473:pathology; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D008597:Menstrual Cycle / Q000276:immunology; D008875:Middle Aged; D018384:Oxidative Stress / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology*; D055815:Young Adult
D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D017382:Reactive Oxygen Species
Endometrial receptivity; endoplasmic reticulum stress; proinflammatory cytokines; regulatory T cells