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      Ovarian Aging-Like Phenotype in the Hyperandrogenism-Induced Murine Model of Polycystic Ovary

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          Abstract

          There are prominently similar symptoms, effectors, and commonalities in the majority of characteristics between ovarian aging and polycystic ovarian syndrome (PCOS). Despite the approved role of oxidative stress in the pathogenesis of PCOS and aging, to our knowledge, the link between the PCO(S) and aging has not been investigated yet. In this study we investigated the possible exhibition of ovarian aging phenotype in murine model of PCO induced by daily oral administration of letrozole (1 mg/kg body weight) for 21 consecutive days in the female Wistar rats. Hyperandrogenization showed irregular cycles and histopathological characteristics of PCO which was associated with a significant increase in lipid peroxidation (LPO) and reactive oxygen species (ROS) and decrease in total antioxidant capacity (TAC) in serum and ovary. Moreover, serum testosterone, insulin and tumor necrosis factor-alpha (TNF- α ) levels, and ovarian matrix metalloproteinase-2 (MMP-2) were increased in PCO rats compared with healthy controls, while estradiol and progesterone diminished. Almost all of these findings are interestingly found to be common with the characteristics identified with (ovarian) aging showing that hyperandrogenism-induced PCO in rat is associated with ovarian aging-like phenotypes. To our knowledge, this is the first report that provides evidence regarding the phenomenon of aging in PCO.

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          Oxidative Stress, Mitochondrial Dysfunction, and Aging

          Hang Cui, Yahui Kong, Hong-Hong Zhang (2011)
          Aging is an intricate phenomenon characterized by progressive decline in physiological functions and increase in mortality that is often accompanied by many pathological diseases. Although aging is almost universally conserved among all organisms, the underlying molecular mechanisms of aging remain largely elusive. Many theories of aging have been proposed, including the free-radical and mitochondrial theories of aging. Both theories speculate that cumulative damage to mitochondria and mitochondrial DNA (mtDNA) caused by reactive oxygen species (ROS) is one of the causes of aging. Oxidative damage affects replication and transcription of mtDNA and results in a decline in mitochondrial function which in turn leads to enhanced ROS production and further damage to mtDNA. In this paper, we will present the current understanding of the interplay between ROS and mitochondria and will discuss their potential impact on aging and age-related diseases.
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            Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis.

            Lisa J. Moran, Marie L Misso, Robert Wild … (2010)
            BACKGROUND Polycystic ovary syndrome (PCOS) is a common condition in reproductive-aged women associated with impaired glucose tolerance (IGT), type 2 diabetes mellitus (DM2) and the metabolic syndrome. METHODS A literature search was conducted (MEDLINE, CINAHL, EMBASE, clinical trial registries and hand-searching) identifying studies reporting prevalence or incidence of IGT, DM2 or metabolic syndrome in women with and without PCOS. Data were presented as odds ratio (OR) [95% confidence interval (CI)] with fixed- and random-effects meta-analysis by Mantel-Haenszel methods. Quality testing was based on Newcastle-Ottawa Scaling and The Cochrane Collaboration's risk of bias assessment tool. Literature searching, data abstraction and quality appraisal were performed by two investigators. RESULTS A total of 2192 studies were reviewed and 35 were selected for final analysis. Women with PCOS had increased prevalence of IGT (OR 2.48, 95% CI 1.63, 3.77; BMI-matched studies OR 2.54, 95% CI 1.44, 4.47), DM2 (OR 4.43, 95% CI 4.06, 4.82; BMI-matched studies OR 4.00, 95% CI 1.97, 8.10) and metabolic syndrome (OR 2.88, 95% CI 2.40, 3.45; BMI-matched studies OR 2.20, 95% CI 1.36, 3.56). One study assessed IGT/DM2 incidence and reported no significant differences in DM2 incidence (OR 2.07, 95% CI 0.68, 6.30). One study assessed conversion from normal glucose tolerance to IGT/DM2 (OR 2.4, 95% CI 0.7, 8.0). No studies reported metabolic syndrome incidence. CONCLUSIONS Women with PCOS had an elevated prevalence of IGT, DM2 and metabolic syndrome in both BMI and non-BMI-matched studies. Few studies have determined IGT/DM2 or metabolic syndrome incidence in women with and without PCOS and further research is required.
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              The effects of oxidative stress on female reproduction: a review

              Ashok Agarwal, Anamar Aponte-Mellado, Beena J Premkumar … (2012)
              Oxidative stress (OS), a state characterized by an imbalance between pro-oxidant molecules including reactive oxygen and nitrogen species, and antioxidant defenses, has been identified to play a key role in the pathogenesis of subfertility in both males and females. The adverse effects of OS on sperm quality and functions have been well documented. In females, on the other hand, the impact of OS on oocytes and reproductive functions remains unclear. This imbalance between pro-oxidants and antioxidants can lead to a number of reproductive diseases such as endometriosis, polycystic ovary syndrome (PCOS), and unexplained infertility. Pregnancy complications such as spontaneous abortion, recurrent pregnancy loss, and preeclampsia, can also develop in response to OS. Studies have shown that extremes of body weight and lifestyle factors such as cigarette smoking, alcohol use, and recreational drug use can promote excess free radical production, which could affect fertility. Exposures to environmental pollutants are of increasing concern, as they too have been found to trigger oxidative states, possibly contributing to female infertility. This article will review the currently available literature on the roles of reactive species and OS in both normal and abnormal reproductive physiological processes. Antioxidant supplementation may be effective in controlling the production of ROS and continues to be explored as a potential strategy to overcome reproductive disorders associated with infertility. However, investigations conducted to date have been through animal or in vitro studies, which have produced largely conflicting results. The impact of OS on assisted reproductive techniques (ART) will be addressed, in addition to the possible benefits of antioxidant supplementation of ART culture media to increase the likelihood for ART success. Future randomized controlled clinical trials on humans are necessary to elucidate the precise mechanisms through which OS affects female reproductive abilities, and will facilitate further explorations of the possible benefits of antioxidants to treat infertility.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Oxid Med Cell Longev
                Journal ID (iso-abbrev): Oxid Med Cell Longev
                Journal ID (publisher-id): OMCL
                Title: Oxidative Medicine and Cellular Longevity
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 1942-0900
                ISSN (Electronic): 1942-0994
                Publication date (Print): 2014
                Publication date (Electronic): 19 February 2014
                Volume: 2014
                Electronic Location Identifier: 948951
                Affiliations
                1Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran
                2Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 1417614411, Iran
                3Centre de Recherche en Biologie de la Reproduction, Université Laval, Québec City, QC, Canada G1V 0A6
                4Faculty of Medicine, Tehran University of Medical Sciences, Tehran 1417614411, Iran
                5Pharmacology and Applied Medicine Department of Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Alborz 141554364, Iran
                6International Campus, Tehran University of Medical Sciences (ICTUMS), Tehran 1417653861, Iran
                Author notes
                *Mohammad Abdollahi: mohammad@ 123456tums.ac.ir

                Academic Editor: Sara Mostafalou

                Article
                DOI: 10.1155/2014/948951
                PMC ID: 3945218
                PubMed ID: 24693338
                SO-VID: de690b3e-cedd-44e2-b30f-605bd67f283f
                Copyright © Copyright © 2014 Mohammad Amin Rezvanfar et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 28 November 2013
                Date accepted : 2 January 2014
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Molecular medicine
                Data availability:
                ScienceOpen disciplines: Molecular medicine

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