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      The Role of Leptin in Fetal Growth during Pre-Eclampsia

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          Abstract

          Leptin is secreted by the placenta and has a multi-facetted role in the regulation of functions related to pregnancy. Metabolic disorders and insufficient homeostatic compensatory mechanisms involving leptin during pregnancy play a decisive role in the development of pre-eclampsia (PE) and give rise to compromised intrauterine growth conditions and aberrant birth weight of offspring. This review was compiled to elucidate the metabolic background of PE and its relationship with adverse intrauterine growth conditions through the examination of leptin as well as to describe possible mechanisms linking leptin to fetal growth restriction. This review illustrates that leptin in PE is dysregulated in maternal, fetal, and placental compartments. There is no single set of unifying mechanisms within the spectrum of PE, and regulatory mechanisms involving leptin are specific to each situation. We conclude that dysregulated leptin is involved in fetal growth at many levels through complex interactions with parallel pregnancy systems and probably throughout the entirety of pregnancy.

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          Most cited references113

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          Positional cloning of the mouse obese gene and its human homologue.

          The mechanisms that balance food intake and energy expenditure determine who will be obese and who will be lean. One of the molecules that regulates energy balance in the mouse is the obese (ob) gene. Mutation of ob results in profound obesity and type II diabetes as part of a syndrome that resembles morbid obesity in humans. The ob gene product may function as part of a signalling pathway from adipose tissue that acts to regulate the size of the body fat depot.
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            Hypertensive Disorders of Pregnancy

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              Pre-eclampsia.

              Pre-eclampsia affects 3-5% of pregnancies and is traditionally diagnosed by the combined presentation of high blood pressure and proteinuria. New definitions also include maternal organ dysfunction, such as renal insufficiency, liver involvement, neurological or haematological complications, uteroplacental dysfunction, or fetal growth restriction. When left untreated, pre-eclampsia can be lethal, and in low-resource settings, this disorder is one of the main causes of maternal and child mortality. In the absence of curative treatment, the management of pre-eclampsia involves stabilisation of the mother and fetus, followed by delivery at an optimal time. Although algorithms to predict pre-eclampsia are promising, they have yet to become validated. Simple preventive measures, such as low-dose aspirin, calcium, and diet and lifestyle interventions, show potential but small benefit. Because pre-eclampsia predisposes mothers to cardiovascular disease later in life, pregnancy is also a window for future health. A collaborative approach to discovery and assessment of the available treatments will hasten our understanding of pre-eclampsia and is an effort much needed by the women and babies affected by its complications.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                27 April 2021
                May 2021
                : 22
                : 9
                : 4569
                Affiliations
                [1 ]Department for Congenital Disorders, Danish National Biobank and Biomarkers, Statens Serum Institute, Artillerivej 5, 2300 Copenhagen, Denmark; PHY@ 123456ssi.dk (P.L.H.); MIC@ 123456ssi.dk (M.C.)
                [2 ]Laboratory of Experimental Cardiology, Department of Biomedical Science, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark; jkanters@ 123456sund.ku.dk
                [3 ]Department of Gynecology and Obstetrics, Copenhagen University Hospital Slagelse, Ingemannsvej 18, 4200 Slagelse, Denmark; idanaeslund@ 123456gmail.com
                [4 ]Department of Obstetrics and Gynecology, University Hospital Hvidovre, Kettegård Alle 30, 2650 Hvidovre, Denmark; lone.krebs@ 123456regionh.dk
                [5 ]Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
                [6 ]Department of Neonatology, University Hospital Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark; ulrik.lausten-thomsen@ 123456regionh.dk
                Author notes
                [* ]Correspondence: victoriadeknegt@ 123456gmail.com ; Tel.: +45-50469429
                Author information
                https://orcid.org/0000-0001-5801-960X
                https://orcid.org/0000-0002-3267-4910
                https://orcid.org/0000-0001-5433-4776
                Article
                ijms-22-04569
                10.3390/ijms22094569
                8123779
                33925454
                cd10eb5a-da19-416b-8ec4-4bf1c2a74c78
                © 2021 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 ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 31 March 2021
                : 26 April 2021
                Categories
                Review

                Molecular biology
                anthropometry,birth weight,fetal development,fetal growth restriction,infant growth,leptin,pre-eclampsia,prenatal growth

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