Immunohistochemical localization of advanced glycation end-products (AGEs) and their receptor (RAGE) in polycystic and normal ovaries

Diamanti-Kandarakis, Evanthia; Piperi, Christina; Patsouris, Efstratios; Korkolopoulou, Penelope; Panidis, Dimitrios; Pawełczyk, Leszek; Papavassiliou, Athanasios G.; Dulęba, Antoni J.

doi:10.1007/s00418-006-0265-3

Cited by 164 publications

(126 citation statements)

References 57 publications

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“…Previous observations have shown increased AGE deposition in granulosa cells from human polycystic ovarian tissue compared to controls [18], whereas in the present study, AGEs seem to localize in theca interna cells of H-AGE-fed normal female rats. It is likely that the source of AGEs, being either endogenous or exogenous, may play a role in localization of AGEs in the ovarian as well as in other tissues, as in the previous immunochemistry study of ovarian tissue, the source of these molecules could not be defined and the type of diet was not known in PCOS patients from which the ovarian tissue was obtained.…”

Section: Discussioncontrasting

confidence: 84%

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Accumulation of dietary glycotoxins in the reproductive system of normal female rats

et al. 2007

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The aim of the present study was to investigate whether dietary advanced glycation end-products (AGEs) can be detected in the ovarian tissue of normal female rats and whether they can affect their metabolic or hormonal profile. Sixty normal rats (20 animals in each group) were randomly assigned to regular diet, either high (H-AGE) or low (L-AGE) in AGE content for 6 months. H-AGE rats demonstrated higher levels of fasting glucose (P<0.001), insulin (P< 0.069), and serum AGEs (P< 0.001) than control and L-AGE rats. Additionally, the H-AGE group showed increased AGE localization in the theca interna cells of the ovarian tissue compared to control/L-AGE rats (P= 0.003). Furthermore, increased receptor for AGE (RAGE) staining was also observed in granulosa cells compared to control/L-AGE samples (P=0.038). In the H-AGE group, plasma testosterone was higher than in control rats (P<0.001) and in the L-AGE group (P<0.001). However, H-AGE rats did not exhibit higher body weight compared with normal (P=0.118) and L-AGE-fed rats (P= 0.35). These results demonstrate for the first time that administration of high AGE diet in female rats for a prolonged period is associated with increased deposition of AGEs in the theca cells and of RAGE in the granulosa and theca interna cells of the ovarian tissue compared with the corresponding ovarian compartments of the control and

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Section: Discussioncontrasting

confidence: 84%

“…In addition, increased immunostaining of AGE and RAGE was observed in the different compartments of the ovarian tissue in polycystic ovaries [18]. Furthermore, young women with PCOS demonstrated increased serum levels of AGEs after receiving a high-AGE diet [19].…”

Section: Introductionmentioning

confidence: 94%

Accumulation of dietary glycotoxins in the reproductive system of normal female rats

et al. 2007

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“…AGEs, which are modified proteins, lipids, or nucleic acids that are nonenzymatically glycated and oxidized by glucose, damage cellular structures and have been implicated in a number of diseases [55]. Research has demonstrated a strong association between the AGE-RAGE (receptor for AGEs) system and certain aspects of PCOS, including obesity [56], insulin resistance [57] [58], granulosa cell dysfunction [59], and adipocyte dysfunction [60]. In their studies using a human granulosa cell line, Diamanti-Kandarakis et al [61] have shown that the AGE-RAGE system could be the cause of the ovulation failure commonly seen in PCOS.…”

Section: Polycystic Ovarian Syndromementioning

confidence: 99%

Vitamin D and assisted reproduction: should vitamin D be routinely screened and repleted prior to ART? A systematic review

Pacis

Fortin

Zarek

et al. 2014

J Assist Reprod Genet

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Purpose To review the current literature regarding the role of vitamin D status in pregnancy outcomes in women undergoing assisted reproductive technology (ART) and to assess cost-effectiveness of routine vitamin D deficiency screening and repletion prior to initiation of ART.Methods A systematic literature review was conducted using PubMed. Relevant study outcomes were compared among the selected studies. A cost-benefit analysis was performed using a decision tree mathematical model with sensitivity analyses from the perspective of direct societal cost. Published data were used to estimate probabilities and costs in 2014 US dollars. Results Thirty-four articles were retrieved, of which eight met inclusion criteria. One study demonstrated a negative relationship between vitamin D status and ART outcomes, while two studies showed no association. The remaining five studies concluded that ART outcomes improved after vitamin D repletion. Conclusion The majority of reviewed studies reported a decrement in ART outcomes in patients with vitamin D deficiency. Cost-benefit analyses suggested that screening and supplementing vitamin D prior to ART might be cost effective, but further evidence is needed. Given the absence of Level I evidence regarding vitamin D status and ART outcomes, full endorsement of routine vitamin D screening and supplementation prior to ART is premature.

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“…NFkB may contribute to the development of a pro-inflammatory and pro-oxidative state by stimulating the expression of numerous target genes, such as tissue factor, vascular cell adhesion molecule-1 (VCAM1), p21Ras, ERK1/2 (MAPK3/1) and RAGE itself (Tanaka et al 2000, Mukhopadhyay & Mukherjee 2005. Furthermore, AGE-RAGE signalling through the activation of NFkB has been reported to regulate the expression of inflammatory cytokines (such as tumour necrosis factor a (TNFa) and interleukin 1), PAI-1 and endothelin-1, contributing to the development of several inflammationrelated conditions and diseases such as atherosclerosis, diabetic nephropathy and retinopathy (Murphy et al 2005, Diamanti-Kandarakis et al 2007b.…”

Section: Introductionmentioning

confidence: 99%

Dietary glycotoxins affect scavenger receptor expression and the hormonal profile of female rats

Chatzigeorgiou¹,

Kandaraki²,

Piperi³

et al. 2013

Journal of Endocrinology

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The levels of advanced glycation end products (AGEs) are increased under conditions of impaired glucose metabolism and/or oxidative stress, promoting insulin resistance and other endocrine abnormalities. AGEs play a major role in the pathogenesis of several diseases such as diabetes, atherosclerosis, polycystic ovary syndrome and Alzheimer's disease, contributing to progressive ageing. Receptor-based clearance of AGEs by the receptor for AGE (RAGE) and/or the macrophage scavenger receptor A (SR-A) is considered as a main factor for the regulation of the concentration of AGEs under these conditions. This study aimed to investigate the expression of RAGE (AGER) and SR-A (MSR1) under high/low-dietary AGE conditions in vivo and their potential contribution to the metabolic and sex hormonal profile of female rats. Female Wistar rats were fed a low-AGE or high-AGE diet for 3 months. Serum samples were collected at baseline and at the completion of the 3-month period for the measurements of metabolic and hormonal parameters. Peripheral blood mononuclear cells (PBMCs) were isolated for the determination of the expression of RAGE and SR-A. The high-AGE diet-fed rats exhibited increased glucose, insulin and testosterone levels as well as decreased oestradiol and progesterone levels compared with the low-AGE diet-fed ones, thus indicating a metabolic and hormonal dysregulation attributed to high-AGE dietary exposure. The expression of RAGE was significantly down-regulated in the PBMCs of the high-AGE diet-fed rats (PZ0.041), and it was correlated negatively with insulin and testosterone levels and positively with progesterone levels. The expression of SR-A was also decreased in the high-AGE diet-fed rats to marginal significance. Decreased monocytic expression of scavenger receptors such as RAGE and SR-A may result in a higher deposition of AGEs in peripheral endocrine tissues, thus promoting endocrine-related abnormalities and diseases.

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Immunohistochemical localization of advanced glycation end-products (AGEs) and their receptor (RAGE) in polycystic and normal ovaries

Cited by 164 publications

References 57 publications

Accumulation of dietary glycotoxins in the reproductive system of normal female rats

Accumulation of dietary glycotoxins in the reproductive system of normal female rats

Vitamin D and assisted reproduction: should vitamin D be routinely screened and repleted prior to ART? A systematic review

Dietary glycotoxins affect scavenger receptor expression and the hormonal profile of female rats

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