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      Mechanisms of Adiponectin Action in Fertility: An Overview from Gametogenesis to Gestation in Humans and Animal Models in Normal and Pathological Conditions

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          Abstract

          Adiponectin is the most abundant plasma adipokine. It mainly derives from white adipose tissue and plays a key role in the control of energy metabolism thanks to its insulin-sensitising, anti-inflammatory, and antiatherogenic properties. In vitro and in vivo evidence shows that adiponectin could also be one of the hormones controlling the interaction between energy balance and fertility in several species, including humans. Indeed, its two receptors—AdipoR1 and AdipoR2—are expressed in hypothalamic–pituitary–gonadal axis and their activation regulates Kiss, GnRH and gonadotropin expression and/or secretion. In male gonads, adiponectin modulates several functions of both somatic and germ cells, such as steroidogenesis, proliferation, apoptosis, and oxidative stress. In females, it controls steroidogenesis of ovarian granulosa and theca cells, oocyte maturation, and embryo development. Adiponectin receptors were also found in placental and endometrial cells, suggesting that this adipokine might play a crucial role in embryo implantation, trophoblast invasion and foetal growth. The aim of this review is to characterise adiponectin expression and its mechanism of action in male and female reproductive tract. Further, since features of metabolic syndrome are associated with some reproductive diseases, such as polycystic ovary syndrome, gestational diabetes mellitus, preeclampsia, endometriosis, foetal growth restriction and ovarian and endometrial cancers, evidence regarding the emerging role of adiponectin in these disorders is also discussed.

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          Global and regional estimates of preeclampsia and eclampsia: a systematic review.

          Reduction of maternal mortality is a target within the Millennium Development Goals. Data on the incidence of preeclampsia and eclampsia, one of the main causes of maternal deaths, are required at both national and regional levels to inform policies. We conducted a systematic review of the incidence of hypertensive disorders of pregnancy (HDP) with the objective of evaluating its magnitude globally and in different regions and settings. We selected studies using pre-specified criteria, recorded database characteristics and assessed methodological quality of the eligible studies reporting incidence of any HDP during the period 2002-2010. A logistic model was then developed to estimate the global and regional incidence of HDP using pre-specified predictor variables where empiric data were not available. We found 129 studies meeting the inclusion criteria, from which 74 reports with 78 datasets reporting HDP were analysed. This represents nearly 39 million women from 40 countries. When the model was applied, the overall estimates are 4.6% (95% uncertainty range 2.7-8.2), and 1.4% (95% uncertainty range 1.0-2.0) of all deliveries for preeclampsia and eclampsia respectively, with a wide variation across regions. The figures we obtained give a general idea of the magnitude of the problem and suggest that some regional variations might exist. The absence of data in many countries is of concern, however, and efforts should be made to implement data collection and reporting for substantial statistics. The implementation of large scale surveys conducted during a short period of time could provide more reliable and up-to-date estimations to inform policy. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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            The Pathophysiology of Gestational Diabetes Mellitus

            Gestational diabetes mellitus (GDM) is a serious pregnancy complication, in which women without previously diagnosed diabetes develop chronic hyperglycemia during gestation. In most cases, this hyperglycemia is the result of impaired glucose tolerance due to pancreatic β-cell dysfunction on a background of chronic insulin resistance. Risk factors for GDM include overweight and obesity, advanced maternal age, and a family history or any form of diabetes. Consequences of GDM include increased risk of maternal cardiovascular disease and type 2 diabetes and macrosomia and birth complications in the infant. There is also a longer-term risk of obesity, type 2 diabetes, and cardiovascular disease in the child. GDM affects approximately 16.5% of pregnancies worldwide, and this number is set to increase with the escalating obesity epidemic. While several management strategies exist—including insulin and lifestyle interventions—there is not yet a cure or an efficacious prevention strategy. One reason for this is that the molecular mechanisms underlying GDM are poorly defined. This review discusses what is known about the pathophysiology of GDM, and where there are gaps in the literature that warrant further exploration.
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              Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ.

              The traditional role attributed to white adipose tissue is energy storage, fatty acids being released when fuel is required. The metabolic role of white fat is, however, complex. For example, the tissue is needed for normal glucose homeostasis and a role in inflammatory processes has been proposed. A radical change in perspective followed the discovery of leptin; this critical hormone in energy balance is produced principally by white fat, giving the tissue an endocrine function. Leptin is one of a number of proteins secreted from white adipocytes, which include angiotensinogen, adipsin, acylation-stimulating protein, adiponectin, retinol-binding protein, tumour neorosis factor a, interleukin 6, plasminogen activator inhibitor-1 and tissue factor. Some of these proteins are inflammatory cytokines, some play a role in lipid metabolism, while others are involved in vascular haemostasis or the complement system. The effects of specific proteins maybe autocrine or paracrine, or the site of action maybe distant from adipose tissue. The most recently described adipocyte secretory proteins are fasting-induced adipose factor, a fibrinogen-angiopoietin-related protein, metallothionein and resistin. Resistin is an adipose tissue-specific factor which is reported to induce insulin resistance, linking diabetes to obesity. Metallothionein is a metal-binding and stress-response protein which may have an antioxidant role. The key challenges in establishing the secretory functions of white fat are to identify the complement of secreted proteins, to establish the role of each secreted protein, and to assess the pathophysiological consequences of changes in adipocyte protein production with alterations in adiposity (obesity, fasting, cachexia). There is already considerable evidence of links between increased production of some adipocyte factors and the metabolic and cardiovascular complications of obesity. In essence, white adipose tissue is a major secretory and endocrine organ involved in a range of functions beyond simple fat storage.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                27 March 2019
                April 2019
                : 20
                : 7
                : 1526
                Affiliations
                [1 ]INRA UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; alix.barbe@ 123456inra.fr (A.B.); alice.bongrani@ 123456inra.fr (A.B.); namya.mellouk@ 123456inra.fr (N.M.); anthony.estienne@ 123456inra.fr (A.E.); jeremy.grandhaye@ 123456inra.fr (J.G.); pascal.froment@ 123456inra.fr (P.F.)
                [2 ]CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; agnieszka.rak@ 123456uj.edu.pl
                [3 ]Université François Rabelais de Tours, F-37041 Tours, France
                [4 ]Department of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University, 31-007 Krakow, Poland; patrycja.kurowska@ 123456doctoral.uj.edu.pl
                [5 ]Assistance Publique des Hôpitaux de Paris, Hôpital Tenon, Service de Biologie de la Reproduction, F-75020 Paris, France; yaelle.elfassy@ 123456hotmail.fr (Y.E.); rachel.levy@ 123456orange.fr (R.L.)
                [6 ]Université Pierre et Marie Curie Paris 6, F-75005 Paris, France
                [7 ]INSERM UMRS_938, Centre de Recherche Saint-Antoine, F-75571 Paris, France
                Author notes
                [* ]Correspondence: Joelle.dupont@ 123456inra.fr ; Tel.: 33-2-4742-7789; Fax: 33-2-4742-7743
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-9572-7151
                Article
                ijms-20-01526
                10.3390/ijms20071526
                6479753
                30934676
                05f67821-59b2-42c5-9cb9-425bbf65601c
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 28 February 2019
                : 22 March 2019
                Categories
                Review

                Molecular biology
                fertility,adipose tissue,reproductive tract,adipokines,cell signaling
                Molecular biology
                fertility, adipose tissue, reproductive tract, adipokines, cell signaling

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