Gut microbiota-derived endotoxin enhanced the incidence of cardia bifida during cardiogenesis

Jing Zhang, Guang Wang, Jia Liu, Lin-rui Gao, Meng Liu, Chao-Jie Wang, Manli Chuai, Yongping Bao, Ge Li, Rui-Man Li, Yu Zhang, Xuesong Yang (Lead / Corresponding author)

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    Background: Cytotoxicity and inflammation-associated toxic responses could be induced by bacterial lipopolysaccharides (LPS) in vitro and in vivo respectively. However, the mechanism involved in LPS-induced cardiac malformation in prenatal fetus is still unknown.

    Methods and results: In this study, we demonstrated that LPS was induced in gut microbiota imbalance mice, and next, LPS exposure during gastrulation in the chick embryo increased the incidence of cardia bifida. Gene transfection and tissue transplantation trajectory indicated that LPS exposure restricted the cell migration of cardiac progenitors to primary heart field in gastrula chick embryos. In vitro explant allograft of GFP-labeled anterior primitive streak demonstrated that LPS treatments could inhibit cell migration. A similar observation was also obtained from the cell migration assay of scratch wounds using primary culture of cardiomyocytes or H9c2 cells. In the embryos exposed to LPS, expressions of Nkx2.5 and GATA5 were disturbed. These genes are associated with cardiomyocyte differentiation when heart tube fusion occurs. Furthermore, pHIS3, C-caspase3 immunohistological staining indicated that cell proliferation decreased, cell apoptosis increased in the heart tube of chick embryo. Meanwhile, in vivo, pHIS3 immunohistological staining and Hochest/PI staining also draw the similar conclusions. The LPS exposure also caused the production of excess ROS, which might damage the cardiac precursor cells of developing embryos. At last, we showed that LPS-induced cardia bifida could be partially rescued through the addition of antioxidants.

    Conclusions: Together, these results reveal that excess ROS generation is involved in the LPS-induced defects in heart tube during chick embryo development. This article is protected by copyright. All rights reserved.

    Original languageEnglish
    Pages (from-to)9271-9283
    Number of pages13
    JournalJournal of Cellular Physiology
    Issue number12
    Early online date8 Sept 2017
    Publication statusPublished - Dec 2018


    • Lipopolysaccharides
    • Chick Embryo
    • Reactive oxygen species
    • Heart Tube


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