Next Article in Journal
Hippocampal Neurogenesis Is Enhanced in Adult Tau Deficient Mice
Previous Article in Journal
Androgen Receptor and Its Splicing Variant 7 Expression in Peripheral Blood Mononuclear Cells and in Circulating Tumor Cells in Metastatic Castration-Resistant Prostate Cancer
Previous Article in Special Issue
Effect of High Glucose-Induced Oxidative Stress on Paraoxonase 2 Expression and Activity in Caco-2 Cells
Open AccessArticle

Methylglyoxal-Dependent Glycative Stress and Deregulation of SIRT1 Functional Network in the Ovary of PCOS Mice

1
Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
2
Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, 00161 Roma, Italy
*
Author to whom correspondence should be addressed.
Cells 2020, 9(1), 209; https://doi.org/10.3390/cells9010209 (registering DOI)
Received: 30 September 2019 / Revised: 10 January 2020 / Accepted: 12 January 2020 / Published: 14 January 2020
(This article belongs to the Special Issue Glycation and Dicarbonyl Stress in Aging and Disease)
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 (PGC1α), 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. View Full-Text
Keywords: PCOS; advanced glycation end-products; methylglyoxal; glycative stress; glyoxalases; SIRT1; SIRT3; oocyte quality; mitochondria; oxidative stress PCOS; advanced glycation end-products; methylglyoxal; glycative stress; glyoxalases; SIRT1; SIRT3; oocyte quality; mitochondria; oxidative stress
Show Figures

Figure 1

MDPI and ACS Style

Di Emidio, G.; Placidi, M.; Rea, F.; Rossi, G.; Falone, S.; Cristiano, L.; Nottola, S.; D’Alessandro, A.M.; Amicarelli, F.; Palmerini, M.G.; Tatone, C. Methylglyoxal-Dependent Glycative Stress and Deregulation of SIRT1 Functional Network in the Ovary of PCOS Mice. Cells 2020, 9, 209.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop