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      Prenatal methamphetamine exposure causes dysfunction in glucose metabolism and low birthweight

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          Abstract

          Methamphetamine (METH) is a psychostimulant drug that induces addiction. Previous epidemiological studies have demonstrated that maternal METH abuse during pregnancy causes low birthweight (LBW) in the offspring. As a source of essential nutrients, in particular glucose, the placenta plays a key role in fetal development. LBW leads to health problems such as obesity, diabetes, and neurodevelopmental disorders (NDDs). However, the detailed mechanism underlying offspring’s LBW and health hazards caused by METH are not fully understood. Therefore, we investigated the effects of prenatal METH exposure on LBW and fetal-placental relationship by focusing on metabolism. We found dysfunction of insulin production in the pancreas of fetuses exposed to METH. We also found a reduction of the glycogen cells (GCs) storing glycogens in the junctional zone of placenta, all of which suggest abnormal glucose metabolism affects the fetal development. These results suggest that dysfunction in fetal glucose metabolism may cause LBW and future health hazards. Our findings provide novel insights into the cause of LBW via the fetal-placental crosstalk.

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          Most cited references32

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          Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales.

          Although the rise in ischaemic heart disease in England and Wales has been associated with increasing prosperity, mortality rates are highest in the least affluent areas. On division of the country into two hundred and twelve local authority areas a strong geographical relation was found between ischaemic heart disease mortality rates in 1968-78 and infant mortality in 1921-25. Of the twenty-four other common causes of death only bronchitis, stomach cancer, and rheumatic heart disease were similarly related to infant mortality. These diseases are associated with poor living conditions and mortality from them is declining. Ischaemic heart disease is strongly correlated with both neonatal and postneonatal mortality. It is suggested that poor nutrition in early life increases susceptibility to the effects of an affluent diet.
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            The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring.

            Viral infection during pregnancy has been correlated with increased frequency of autism spectrum disorder (ASD) in offspring. This observation has been modeled in rodents subjected to maternal immune activation (MIA). The immune cell populations critical in the MIA model have not been identified. Using both genetic mutants and blocking antibodies in mice, we show that retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt)-dependent effector T lymphocytes [for example, T helper 17 (TH17) cells] and the effector cytokine interleukin-17a (IL-17a) are required in mothers for MIA-induced behavioral abnormalities in offspring. We find that MIA induces an abnormal cortical phenotype, which is also dependent on maternal IL-17a, in the fetal brain. Our data suggest that therapeutic targeting of TH17 cells in susceptible pregnant mothers may reduce the likelihood of bearing children with inflammation-induced ASD-like phenotypes.
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              Growth and function of the normal human placenta.

              The placenta is the highly specialised organ of pregnancy that supports the normal growth and development of the fetus. Growth and function of the placenta are precisely regulated and coordinated to ensure the exchange of nutrients and waste products between the maternal and fetal circulatory systems operates at maximal efficiency. The main functional units of the placenta are the chorionic villi within which fetal blood is separated by only three or four cell layers (placental membrane) from maternal blood in the surrounding intervillous space. After implantation, trophoblast cells proliferate and differentiate along two pathways described as villous and extravillous. Non-migratory, villous cytotrophoblast cells fuse to form the multinucleated syncytiotrophoblast, which forms the outer epithelial layer of the chorionic villi. It is at the terminal branches of the chorionic villi that the majority of fetal/maternal exchange occurs. Extravillous trophoblast cells migrate into the decidua and remodel uterine arteries. This facilitates blood flow to the placenta via dilated, compliant vessels, unresponsive to maternal vasomotor control. The placenta acts to provide oxygen and nutrients to the fetus, whilst removing carbon dioxide and other waste products. It metabolises a number of substances and can release metabolic products into maternal and/or fetal circulations. The placenta can help to protect the fetus against certain xenobiotic molecules, infections and maternal diseases. In addition, it releases hormones into both the maternal and fetal circulations to affect pregnancy, metabolism, fetal growth, parturition and other functions. Many placental functional changes occur that accommodate the increasing metabolic demands of the developing fetus throughout gestation.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                24 October 2022
                2022
                : 13
                : 1023984
                Affiliations
                [1] 1 Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University , Suita, Japan
                [2] 2 Addiction Research Unit, Osaka Psychiatric Research Center, Osaka Psychiatric Medical Center , Osaka, Japan
                [3] 3 Department of Cell Biology, Graduate School of Medicine, Osaka University , Osaka, Japan
                [4] 4 United Graduate School of Child Development, Osaka University , Suita, Japan
                [5] 5 Global Center for Medical Engineering and Informatics, Osaka University , Suita, Japan
                Author notes

                Edited by: Hiroaki Itohm, Hamamatsu University School of Medicine, Japan

                Reviewed by: Yoshitsugu Chigusa, Kyoto University, Japan; Keiichi Matsubara, Ehime University, Japan; Satoru Ikenoue, Keio University School of Medicine, Japan; Akio Nakamura, Jissen Women’s University, Japan

                *Correspondence: Noriyoshi Usui, usui@ 123456anat1.med.osaka-u.ac.jp

                This article was submitted to Experimental Endocrinology, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2022.1023984
                9637823
                a2a5b1ff-9b6b-49c8-8567-43ce066696c2
                Copyright © 2022 Doi, Nakama, Sumi, Usui and Shimada

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 August 2022
                : 13 October 2022
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 32, Pages: 8, Words: 3350
                Funding
                Funded by: Japan Society for the Promotion of Science , doi 10.13039/501100001691;
                Award ID: 20K06872, 20K21654
                Funded by: Osaka Medical Research Foundation for Intractable Diseases , doi 10.13039/501100008665;
                Categories
                Endocrinology
                Original Research

                Endocrinology & Diabetes
                methamphetamine,addiction,drug abuse,low birthweight (lbw),metabolism,placenta,embryonic development

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