Immunohistochemical localization of advanced glycation end-products (AGEs) and their receptor (RAGE) in polycystic and normal ovaries |
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Authors: | Evanthia Diamanti-Kandarakis Christina Piperi Efstratios Patsouris Penelope Korkolopoulou Dimitrios Panidis Leszek Pawelczyk Athanasios G Papavassiliou Antoni J Duleba |
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Institution: | (1) First Department of Internal Medicine, Endocrine section, University of Athens Medical School, 75, M. Asias Str., 11527 Athens, Greece;(2) Department of Biological Chemistry, University of Athens Medical School, 75, M. Asias Str., 11527 Athens, Greece;(3) Department of Pathology, University of Athens Medical School, 75, M. Asias Str., 11527 Athens, Greece;(4) Division of Endocrinology and Human Reproduction, Second Department of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece;(5) Division of Infertility and Reproductive Endocrinology, Department of Gynecology and Obstetrics, Karol Marcinkowski University of Medical Sciences, Poznan, Poland;(6) Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT, USA;(7) 1A Zefyrou Str., Ekali, 17562 Athens, Greece |
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Abstract: | The aim of the present study was to investigate the localization/immunohistochemical distribution of AGEs and RAGE, as well
as their putative signalling mediator NF-κB in ovaries of women with polycystic ovary syndrome (PCOS) compared to normal.
Archival ovarian-tissue samples from biopsies of six women with PCOS and from six healthy of similar age women, were examined
immunohistochemically with monoclonal anti-AGEs, anti-RAGE and anti-NF-κB(p50/p65) specific antibodies. In healthy women,
AGE immunoreactivity was observed in follicular cell layers (granulosa and theca) and luteinized cells, but not in endothelial
cells. PCOS specimens displayed AGE immunoexpression in theca interna and granulosa cells as well as in endothelial cells,
but staining of granulosa cells was stronger than in that of normal ovaries. RAGE was highly expressed in normal and PCOS
tissues. Normal tissue exhibited no staining differences between granulosa cell layer and theca interna. However, in PCOS
ovaries, granulosa cells displayed stronger RAGE expression compared to theca interna cells in comparison to controls. NF-κB(p50/p65)
was expressed in the cytoplasm of theca interna and granulosa cells of both normal and PCOS ovaries; whereas the NF-κB p65
subunit was only observed in granulosa cells nuclei in PCOS tissue. In conclusion, these findings demonstrate for the first
time that RAGE and AGE-modified proteins with activated NF-κB are expressed in human ovarian tissue. Furthermore, a differential
qualitative distribution of AGE, RAGE and NF-κB p65 subunit was observed in women with PCOS compared to healthy controls,
where a stronger localization of both AGE and RAGE was observed in the granulosa cell layer of PCOS ovaries. |
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Keywords: | Advanced glycation end-products NF-κ B Ovaries PCOS RAGE |
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