+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Decreased ovarian reserve, dysregulation of mitochondrial biogenesis, and increased lipid peroxidation in female mouse offspring exposed to an obesogenic maternal diet


      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Maternal diet during pregnancy influences the later life reproductive potential of female offspring. We investigate the molecular mechanisms underlying the depletion of ovarian follicular reserve in young adult females following exposure to obesogenic diet in early life. Furthermore, we explore the interaction between adverse maternal diet and postweaning diet in generating reduced ovarian reserve. Female mice were exposed to either maternal obesogenic (high fat/high sugar) or maternal control diet in utero and during lactation, then weaned onto either obesogenic or control diet. At 12 wk of age, the offspring ovarian reserve was depleted following exposure to maternal obesogenic diet ( P < 0.05), but not postweaning obesogenic diet. Maternal obesogenic diet was associated with increased mitochondrial DNA biogenesis (copy number P < 0.05; transcription factor A, mitochondrial expression P < 0.05), increased mitochondrial antioxidant defenses [manganese superoxide dismutase ( MnSOD) P < 0.05; copper/zinc superoxide dismutase P < 0.05; glutathione peroxidase 4 P < 0.01] and increased lipoxygenase expression (arachidonate 12-lipoxygenase P < 0.05; arachidonate 15-lipoxygenase P < 0.05) in the ovary. There was also significantly increased expression of the transcriptional regulator NF-κB ( P < 0.05). There was no effect of postweaning diet on any measured ovarian parameters. Maternal diet thus plays a central role in determining follicular reserve in adult female offspring. Our observations suggest that lipid peroxidation and mitochondrial biogenesis are the key intracellular pathways involved in programming of ovarian reserve.—Aiken, C. E., Tarry-Adkins, J. L., Penfold, N. C., Dearden, L., Ozanne, S. E. Decreased ovarian reserve, dysregulation of mitochondrial biogenesis, and increased lipid peroxidation in female mouse offspring exposed to an obesogenic maternal diet.

          Related collections

          Most cited references38

          • Record: found
          • Abstract: found
          • Article: not found

          Lipid peroxidation: physiological levels and dual biological effects.

          Etsuo Niki (2009)
          Lipid peroxidation (LPO) has been shown to induce disturbance of membrane organization and functional loss and modification of proteins and DNA bases, and it has been implicated in the pathogenesis of various diseases. At the same time, LPO products have been shown to act as redox signaling mediators. Free and ester forms of both polyunsaturated fatty acids and cholesterol are important substrates for LPO in vivo and they are oxidized by both enzymatic and nonenzymatic mechanisms to give a variety of products. The results of numerous studies reported in the literatures show that the levels of LPO products in plasma of healthy human subjects are below 1 muM and that the molar ratios of LPO products to the respective parent lipids are below 1/1000, that is, below 0.1%. The levels of LPO products in human erythrocytes were found to be higher than those in plasma. Considerable levels of cholesterol oxidation products were observed. Although many LPO products exert cytotoxicity, sublethal concentrations of LPO products induce cellular adaptive responses and enhance tolerance against subsequent oxidative stress through upregulation of antioxidant compounds and enzymes. This adaptive response is observed not only for chemically reactive alpha,beta-unsaturated carbonyl compounds such as 4-hydroxy-2-nonenal and 15-deoxy-delta-12,14-prostaglandin J(2) but also for chemically stable compounds such as hydroxyoctadecadienoic acid, hydroxylcholesterol, and lysophosphatidylcholine. Such opposite dual functions of LPO products imply that LPO, and probably oxidative stress in general, may exert both deleterious and beneficial effects in vivo. LPO as well as reactive oxygen and nitrogen species has been shown to play an important role as a regulator of gene expression and cellular signaling messenger. In order to exert physiologically important functions as a regulator of gene expression and mediator of cellular signaling, the formation of LPO products must be strictly controlled and programmed. In contrast to LPO products by enzymatic oxidation, it appears difficult to regulate the formation of free radical-mediated LPO products. Even such unregulated LPO products may exert beneficial effects at low levels, but excessive unregulated LPO may lead to pathological disorders and diseases.
            • Record: found
            • Abstract: found
            • Article: not found

            Maternal body mass index and the risk of fetal death, stillbirth, and infant death: a systematic review and meta-analysis.

            Evidence suggests that maternal obesity increases the risk of fetal death, stillbirth, and infant death; however, the optimal body mass index (BMI) for prevention is not known. To conduct a systematic review and meta-analysis of cohort studies of maternal BMI and risk of fetal death, stillbirth, and infant death. The PubMed and Embase databases were searched from inception to January 23, 2014. Cohort studies reporting adjusted relative risk (RR) estimates for fetal death, stillbirth, or infant death by at least 3 categories of maternal BMI were included. Data were extracted by 1 reviewer and checked by the remaining reviewers for accuracy. Summary RRs were estimated using a random-effects model. Fetal death, stillbirth, and neonatal, perinatal, and infant death. Thirty eight studies (44 publications) with more than 10,147 fetal deaths, more than 16,274 stillbirths, more than 4311 perinatal deaths, 11,294 neonatal deaths, and 4983 infant deaths were included. The summary RR per 5-unit increase in maternal BMI for fetal death was 1.21 (95% CI, 1.09-1.35; I2 = 77.6%; n = 7 studies); for stillbirth, 1.24 (95% CI, 1.18-1.30; I2 = 80%; n = 18 studies); for perinatal death, 1.16 (95% CI, 1.00-1.35; I2 = 93.7%; n = 11 studies); for neonatal death, 1.15 (95% CI, 1.07-1.23; I2 = 78.5%; n = 12 studies); and for infant death, 1.18 (95% CI, 1.09-1.28; I2 = 79%; n = 4 studies). The test for nonlinearity was significant in all analyses but was most pronounced for fetal death. For women with a BMI of 20 (reference standard for all outcomes), 25, and 30, absolute risks per 10,000 pregnancies for fetal death were 76, 82 (95% CI, 76-88), and 102 (95% CI, 93-112); for stillbirth, 40, 48 (95% CI, 46-51), and 59 (95% CI, 55-63); for perinatal death, 66, 73 (95% CI, 67-81), and 86 (95% CI, 76-98); for neonatal death, 20, 21 (95% CI, 19-23), and 24 (95% CI, 22-27); and for infant death, 33, 37 (95% CI, 34-39), and 43 (95% CI, 40-47), respectively. Even modest increases in maternal BMI were associated with increased risk of fetal death, stillbirth, and neonatal, perinatal, and infant death. Weight management guidelines for women who plan pregnancies should take these findings into consideration to reduce the burden of fetal death, stillbirth, and infant death.
              • Record: found
              • Abstract: found
              • Article: not found

              Mammalian lipoxygenases and their biological relevance.

              Lipoxygenases (LOXs) form a heterogeneous class of lipid peroxidizing enzymes, which have been implicated not only in cell proliferation and differentiation but also in the pathogenesis of various diseases with major public health relevance. As other fatty acid dioxygenases LOXs oxidize polyunsaturated fatty acids to their corresponding hydroperoxy derivatives, which are further transformed to bioactive lipid mediators (eicosanoids and related substances). On the other hand, lipoxygenases are key players in the regulation of the cellular redox homeostasis, which is an important element in gene expression regulation. Although the first mammalian lipoxygenases were discovered 40 years ago and although the enzymes have been well characterized with respect to their structural and functional properties the biological roles of the different lipoxygenase isoforms are not completely understood. This review is aimed at summarizing the current knowledge on the physiological roles of different mammalian LOX-isoforms and their patho-physiological function in inflammatory, metabolic, hyperproliferative, neurodegenerative and infectious disorders. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance".

                Author and article information

                FASEB J
                FASEB J
                The FASEB Journal
                Federation of American Societies for Experimental Biology (Bethesda, MD, USA )
                April 2016
                23 December 2015
                23 December 2015
                : 30
                : 4
                : 1548-1556
                University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital and National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre, Cambridge, United Kingdom
                Author notes
                [1 ]Correspondence: University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, Level 4, Box 289, Addenbrooke’s Treatment Centre, Addenbrooke’s Hospital, Hills Rd., Cambridge, CB2 OQQ, United Kingdom. E-mail: cema2@ 123456cam.ac.uk
                © The Author(s)

                This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) ( http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                : 02 October 2015
                : 08 December 2015
                Page count
                Pages: 9
                Research Communication
                Custom metadata

                Molecular biology
                developmental programming,reproductive potential,primordial follicle,lipoxygenase


                Comment on this article