Developmental regulation of the intestinal FGF19 system in domestic pigs
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Authors: Gavalda-Navarro, Aleix; Pastor, Jose J.; Mereu, Alessandro; Villarroya, Francesc; Ipharraguerre, Ignacio R.
Abstract
Fibroblast growth factor-19 (FGF19) is an emerging endocrine factor involved in the regulation ol bile acid Homeostasis and energy metabolism in rodents and humans. In pigs, however, the FGF19 system remains largely unexplored. This study was designed to investigate the developmental regulation of the FGF19 system in domestic pigs. Samples of intestinal sections, liver, and plasma were collected from 24 pigs (n = 6) at four developmental stages (birth, preweaning, postweaning, and adulthood). In the intestine, expression of the farnesoid X receptor (FXR) and FGF19 showed a congruent time- and region-dependent regulation, beginning soon after birth to achieve maximal expression in ileum during adulthood. The same temporal pattern was followed by the circulating concentration of FGF19, and these changes were accompanied by a time-related increase in the ileal proportion of bile acids that potently activate FXR. Conversely, genes belonging to the FGF19 signaling machinery achieved maximal expression in the small intestine at birth to decrease sharply afterward. In the liver, gene expression of FGF19 receptors and enzymes involved in bile acid biosynthesis paralleled after-birth changes in plasma concentration of this enterokine and attained a maximum during postweaning when plasma FGF19 was the lowest. Although detectable at birth, the hepatic expression of genes belonging to the bile acid-FXR-FGF 19 pathway was low before the onset of enteral feeding. In summary, the porcine FGF19 system is present from birth, operative before the onset of enteral feeding, and regulated in a temporal and section-specific manner. NEW & NOTEWORTHY Fibroblast growth factor-19 (FGF19) is an emerging endocrine factor. The domestic pig is a translational model of value in biomedical research. We show for the first time that in pigs the intestinal FGF19 system is present from birth, operative before the onset of enteral feeding, and regulated in a temporal and section-specific manner. This work identifies pigs as a suitable model for investigating the implications of FGF19 signaling within and beyond the gut-liver axis.
Exposure to prothioconazole induces developmental toxicity and cardiovascular effects on zebrafish embryo
CHEMOSPHERE
Authors: Sun, Yongqi; Cao, Yi; Tong, Lili; Tao, Fangyi; Wang, Xiaonan; Wu, Huiming; Wang, Mengcen
Abstract
Prothioconazole is a fungicide that has been widely used in general agriculture and livestock husbandry. This study evaluated the acute toxicity of prothioconazole to zebrafish embryos by assessing their hatching rate and malformation when exposed to different concentrations of prothioconazole. The 96 h-LC50 value of zebrafish embryos was 1.70 mg/L. Upon exposure to 0.85 mg/L, the mortality rate of the embryos significantly increased while their hatching rate decreased significantly. At prothioconazole concentrations higher than 0.43 mg/L, developmental morphologic abnormalities such as heart and yolksac edema, spine curvature, tail deformity, shortened body length and decreased eye area were observed. The heart rate of embryos decreased in a dose-dependent fashion during the exposure time. Prothioconazole exposure also resulted in increased rates of cardiac malformation detected by significant increase in the distance between the sinus venosus and bulbus arteriosus and the pericardium area. Moreover, the expression levels of genes related to cardiac development (amhc, vmhc, fli1, hand2, gata4, nkx2.5, tbx5 and atp2a2a) were significantly altered after exposure to prothioconazole. Indeed, this study revealed the adverse effects on the developmental and cardiovascular system of zebrafish embryo caused by prothioconazole. It further elucidated the risk of prothioconazole exposure to vertebrate cardiovascular toxicity. As such, it provides a theoretical foundation for pesticide risk management measures. (C) 2020 Elsevier Ltd. All rights reserved.