Methylglyoxal-dependent glycative stress and deregulation of SIRT1 functional network in the ovary of PCOS mice

Advanced glycation end-products (AGEs) are involved in the pathogenesis and consequences of polycystic ovary syndrome (PCOS), a complex metabolic disorder associated with female infertility. The most powerful AGE precursor is methylglyoxal (MG), a byproduct of glycolysis, that is detoxified by the glyoxalase system. By using a PCOS mouse model induced by administration of dehydroepiandrosterone (DHEA), we investigated whether MG-dependent glycative stress contributes to ovarian PCOS phenotype and explored changes in the Sirtuin 1 (SIRT1) functional network regulating mitochondrial functions and cell survival. In addition to anovulation and reduced oocyte quality, DHEA ovaries revealed altered collagen deposition, increased vascularization, lipid droplets accumulation and altered steroidogenesis. Here we observed increased intraovarian MG-AGE levels in association with enhanced expression of receptor for AGEs (RAGEs) and deregulation of the glyoxalase system, hallmarks of glycative stress. Moreover, DHEA mice exhibited enhanced ovarian expression of SIRT1 along with increased protein levels of SIRT3 and superoxide dismutase 2 (SOD2), and decreased peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC1 alpha), mitochondrial transcriptional factor A (mtTFA) and translocase of outer mitochondrial membrane 20 (TOMM20). Finally, the presence of autophagy protein markers and increased AMP-activated protein kinase (AMPK) suggested the involvement of SIRT1/AMPK axis in autophagy activation. Overall, present findings demonstrate that MG-dependent glycative stress is involved in ovarian dysfunctions associated to PCOS and support the hypothesis of a SIRT1-dependent adaptive response

A meta-analysis of the impacts of genetically modified crops.

BACKGROUND: Despite the rapid adoption of genetically modified (GM) crops by farmers in many countries, controversies about this technology continue. Uncertainty about GM crop impacts is one reason for widespread public suspicion. OBJECTIVE: We carry out a meta-analysis of the agronomic and economic impacts of GM crops to consolidate the evidence. DATA SOURCES: Original studies for inclusion were identified through keyword searches in ISI Web of Knowledge, Google Scholar, EconLit, and AgEcon Search. STUDY ELIGIBILITY CRITERIA: Studies were included when they build on primary data from farm surveys or field trials anywhere in the world, and when they report impacts of GM soybean, maize, or cotton on crop yields, pesticide use, and/or farmer profits. In total, 147 original studies were included. SYNTHESIS METHODS: Analysis of mean impacts and meta-regressions to examine factors that influence outcomes. RESULTS: On average, GM technology adoption has reduced chemical pesticide use by 37%, increased crop yields by 22%, and increased farmer profits by 68%. Yield gains and pesticide reductions are larger for insect-resistant crops than for herbicide-tolerant crops. Yield and profit gains are higher in developing countries than in developed countries. LIMITATIONS: Several of the original studies did not report sample sizes and measures of variance. CONCLUSION: The meta-analysis reveals robust evidence of GM crop benefits for farmers in developed and developing countries. Such evidence may help to gradually increase public trust in this technology.Open Access Publikationsfonds 2014peerReviewe