Systemic inflammation, cellular influx and up-regulation of ovarian VCAM-1 expression in a mouse model of polycystic ovary syndrome (PCOS).
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Systemic inflammation, cellular influx and up-regulation of ovarian VCAM-1 expression in a mouse model of polycystic ovary syndrome (PCOS). / Solano, Maria Emilia; Sander, Valeria Analía; Ho, Hoang; Motta, Alicia Beatriz; Arck, Petra.
In: J REPROD IMMUNOL, Vol. 92, No. 1-2, 1-2, 2011, p. 33-44.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Systemic inflammation, cellular influx and up-regulation of ovarian VCAM-1 expression in a mouse model of polycystic ovary syndrome (PCOS).
AU - Solano, Maria Emilia
AU - Sander, Valeria Analía
AU - Ho, Hoang
AU - Motta, Alicia Beatriz
AU - Arck, Petra
PY - 2011
Y1 - 2011
N2 - PCOS, a major cause of anovulatory sterility, is associated with obesity, insulin resistance and chronic inflammation. New evidence suggests that the immune system aggravates the clinical features of PCOS. Our aim was to study the immune, metabolic and endocrine features of a mouse model of PCOS elicited by androgenisation using dehydroepiandrosterone (DHEA). We observed a significant weight gain and insulin resistance in DHEA-androgenised mice, coupled with the formation of ovarian follicular cysts. DHEA up-regulated the expression of vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 in the granulosa cell layer of the majority of cysts, and VCAM-1 expression in the theca cell layer of all follicles and cysts. The expression of these markers was low in control tissue. Peritoneal cells from PCOS-mice showed enhanced production of inflammatory cytokines, suggesting an association between chronic inflammation and PCOS. In addition, DHEA-androgenisation induced the activation of CD4(+) cells both in vivo and in vitro, and their expression of the respective ligands for VCAM-1 and ICAM-1, VLA-4 and LFA-1, as assessed in vitro. CD4(+) cells were present in androgenised ovaries, especially in the granulosa cell layer of cysts with high VCAM-1 expression. Herein, we present novel evidence that the immune system is activated systemically and locally in a mouse model for PCOS. We propose that VCAM-1 is involved in aggravating PCOS symptoms by promoting leukocyte recruitment to the ovaries and perpetuating local inflammation. These findings offer novel therapeutic opportunities for PCOS, such as blockage of VCAM-1 expression.
AB - PCOS, a major cause of anovulatory sterility, is associated with obesity, insulin resistance and chronic inflammation. New evidence suggests that the immune system aggravates the clinical features of PCOS. Our aim was to study the immune, metabolic and endocrine features of a mouse model of PCOS elicited by androgenisation using dehydroepiandrosterone (DHEA). We observed a significant weight gain and insulin resistance in DHEA-androgenised mice, coupled with the formation of ovarian follicular cysts. DHEA up-regulated the expression of vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 in the granulosa cell layer of the majority of cysts, and VCAM-1 expression in the theca cell layer of all follicles and cysts. The expression of these markers was low in control tissue. Peritoneal cells from PCOS-mice showed enhanced production of inflammatory cytokines, suggesting an association between chronic inflammation and PCOS. In addition, DHEA-androgenisation induced the activation of CD4(+) cells both in vivo and in vitro, and their expression of the respective ligands for VCAM-1 and ICAM-1, VLA-4 and LFA-1, as assessed in vitro. CD4(+) cells were present in androgenised ovaries, especially in the granulosa cell layer of cysts with high VCAM-1 expression. Herein, we present novel evidence that the immune system is activated systemically and locally in a mouse model for PCOS. We propose that VCAM-1 is involved in aggravating PCOS symptoms by promoting leukocyte recruitment to the ovaries and perpetuating local inflammation. These findings offer novel therapeutic opportunities for PCOS, such as blockage of VCAM-1 expression.
KW - Animals
KW - Humans
KW - Female
KW - Cells, Cultured
KW - Disease Models, Animal
KW - Mice
KW - Mice, Inbred BALB C
KW - Gene Expression Regulation/drug effects
KW - CD4-Positive T-Lymphocytes/drug effects/metabolism/pathology
KW - Cell Movement/drug effects
KW - Cytokines/genetics/metabolism
KW - Dehydroepiandrosterone/administration & dosage
KW - Inflammation Mediators/metabolism
KW - Integrin alpha4beta1/genetics/metabolism
KW - Intercellular Adhesion Molecule-1/genetics/metabolism
KW - Lymphocyte Function-Associated Antigen-1/genetics/metabolism
KW - Ovary/pathology
KW - Peritoneum/drug effects/metabolism/pathology
KW - Polycystic Ovary Syndrome/immunology
KW - Vascular Cell Adhesion Molecule-1/genetics/metabolism
KW - Animals
KW - Humans
KW - Female
KW - Cells, Cultured
KW - Disease Models, Animal
KW - Mice
KW - Mice, Inbred BALB C
KW - Gene Expression Regulation/drug effects
KW - CD4-Positive T-Lymphocytes/drug effects/metabolism/pathology
KW - Cell Movement/drug effects
KW - Cytokines/genetics/metabolism
KW - Dehydroepiandrosterone/administration & dosage
KW - Inflammation Mediators/metabolism
KW - Integrin alpha4beta1/genetics/metabolism
KW - Intercellular Adhesion Molecule-1/genetics/metabolism
KW - Lymphocyte Function-Associated Antigen-1/genetics/metabolism
KW - Ovary/pathology
KW - Peritoneum/drug effects/metabolism/pathology
KW - Polycystic Ovary Syndrome/immunology
KW - Vascular Cell Adhesion Molecule-1/genetics/metabolism
U2 - 10.1016/j.jri.2011.09.003
DO - 10.1016/j.jri.2011.09.003
M3 - SCORING: Journal article
VL - 92
SP - 33
EP - 44
JO - J REPROD IMMUNOL
JF - J REPROD IMMUNOL
SN - 0165-0378
IS - 1-2
M1 - 1-2
ER -