CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
artículos
Título:
Systemic inflammation, cellular influx and up-regulation of ovarian VCAM-1 expression in a mouse model of polycystic ovary syndrome (PCOS)
Autor/es:
MARIA EMILIA SOLANO; VALERIA SANDER; HO HOANG; PETRA ARCK ; ALICIA BEATRIZ MOTTA
Revista:
JOURNAL OF REPRODUCTIVE IMMUNOLOGY.
Editorial:
ELSEVIER IRELAND LTD
Referencias:
Año: 2011 vol. 92 p. 33 - 44
ISSN:
0165-0378
Resumen:
PCOS, a major cause for anovulatory sterility, is associated with obesity, insulin resistanceand chronic inflammation. New evidence suggests that immune system aggravates the clinical features of PCOS. Therefore, our aim was to study immune, metabolic and endocrine features in a mouse model of PCOS by androgenisation using dehydroepiandrosterone (DHEA).We observed a significant weight gain and insulin resistance in DHEA-androgenized mice, couple with the formation of ovarian follicular cysts. Further, 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 the 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-androgenization induced the activation of CD4+ cells both in vivo and in vitro, and their expression of the respective ligand for VCAM-1 and ICAM-1, VLA-4 and LFA-1, as assessed in vitro. We could further confirm that CD4+ cells were present in androgenized ovaries, especially in the GCL of cysts with high VCAM-1 expression. Herein, we present novel evidence that the immune system is activated on systemic and local levels 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.