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Title: In Utero Exposure to Mercury Is Associated With Increased Susceptibility to Liver Injury and Inflammation in Childhood.

Authors: Stratakis, Nikos; Golden-Mason, Lucy; Margetaki, Katerina; Zhao, Yinqi; Valvi, Damaskini; Garcia, Erika; Maitre, Léa; Andrusaityte, Sandra; Basagana, Xavier; Borràs, Eva; Bustamante, Mariona; Casas, Maribel; Fossati, Serena; Grazuleviciene, Regina; Haug, Line Småstuen; Heude, Barbara; McEachan, Rosemary R C; Meltzer, Helle Margrete; Papadopoulou, Eleni; Roumeliotaki, Theano; Robinson, Oliver; Sabidó, Eduard; Urquiza, Jose; Vafeiadi, Marina; Varo, Nerea; Wright, John; Vos, Miriam B; Hu, Howard; Vrijheid, Martine; Berhane, Kiros T; Conti, David V; McConnell, Rob; Rosen, Hugo R; Chatzi, Lida

Published In Hepatology, (2021 Sep)

Abstract: BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of liver disease in children. Mercury (Hg), a ubiquitous toxic metal, has been proposed as an environmental factor contributing to toxicant-associated fatty liver disease. APPROACH AND RESULTS: We investigated the effect of prenatal exposure to Hg on childhood liver injury by combining epidemiological results from a multicenter mother-child cohort with complementary in vitro experiments on monocyte cells that are known to play a key role in liver immune homeostasis and NAFLD. We used data from 872 mothers and their children (median age, 8.1 years; interquartile range [IQR], 6.5-8.7) from the European Human Early-Life Exposome cohort. We measured Hg concentration in maternal blood during pregnancy (median, 2.0 μg/L; IQR, 1.1-3.6). We also assessed serum levels of alanine aminotransferase (ALT), a common screening tool for pediatric NAFLD, and plasma concentrations of inflammation-related cytokines in children. We found that prenatal Hg exposure was associated with a phenotype in children that was characterized by elevated ALT (≥22.1 U/L for females and ≥25.8 U/L for males) and increased concentrations of circulating IL-1β, IL-6, IL-8, and TNF-α. Consistently, inflammatory monocytes exposed in vitro to a physiologically relevant dose of Hg demonstrated significant up-regulation of genes encoding these four cytokines and increased concentrations of IL-8 and TNF-α in the supernatants. CONCLUSIONS: These findings suggest that developmental exposure to Hg can contribute to inflammation and increased NAFLD risk in early life.

PubMed ID: 33730435 Exiting the NIEHS site

MeSH Terms: Adult; Alanine Transaminase; Child; Cohort Studies; Cytokines; Disease Susceptibility; Exposome; Female; Humans; Inflammation; Interleukin-1beta/genetics; Interleukin-1beta/metabolism; Interleukin-6/genetics; Interleukin-6/metabolism; Interleukin-8/genetics; Interleukin-8/metabolism; Male; Maternal Exposure; Mercury/blood*; Non-alcoholic Fatty Liver Disease/epidemiology*; Non-alcoholic Fatty Liver Disease/genetics; Non-alcoholic Fatty Liver Disease/metabolism; Pregnancy; Prenatal Exposure Delayed Effects/epidemiology*; Prenatal Exposure Delayed Effects/genetics; Prenatal Exposure Delayed Effects/metabolism; Tumor Necrosis Factor-alpha/genetics; Tumor Necrosis Factor-alpha/metabolism

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