Constitutive Androstane Receptor Agonist, TCPOBOP: Maternal Exposure Impairs the Growth and Development of Female Offspring in Mice

被引:2
|
作者
Pan, Shijia [1 ,2 ]
Guo, Yuan [1 ,2 ]
Yu, Wen [1 ,2 ]
Zhang, Jia [1 ,2 ]
Qiao, Xiaoxiao [1 ,2 ]
Li, Letong [1 ,2 ]
Xu, Pengfei [3 ,4 ,5 ]
Zhai, Yonggong [1 ,2 ]
机构
[1] Beijing Normal Univ, Coll Life Sci, Beijing Key Lab Gene Resource & Mol Dev, Beijing 100875, Peoples R China
[2] Beijing Normal Univ, Coll Life Sci, Key Lab Cell Proliferat & Regulat Biol State Educ, Beijing 100875, Peoples R China
[3] Wuhan Univ, Sch Pharmaceut Sci, Wuhan 430071, Peoples R China
[4] Univ Pittsburgh, Ctr Pharmacogenet, Pittsburgh, PA 15261 USA
[5] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA
基金
中国国家自然科学基金;
关键词
maternal exposure; offspring health; constitutive androstane receptor; TCPOBOP; growth inhibition; lipid absorption; OXIDATIVE STRESS; INTESTINAL INJURY; NUCLEAR RECEPTORS; ACTIVATION; LIVER; CAR; INDUCTION; MODEL; INFLAMMATION; MICROBIOTA;
D O I
10.3390/ijms24032602
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Environmental chemicals, which are known to impact offspring health, have become a public concern. Constitutive activated receptor (CAR) is activated by various environmental chemicals and participates in xenobiotic metabolism. Here, we described the effects of maternal exposure to the CAR-specific ligand 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP, TC) on offspring health outcomes. Maternal TC exposure exhibited a stronger inhibition of body weight in 3-week-old and 8-week-old first-generation (F1) offspring female mice compared to controls. Further, maternal TC exposure obtained a strong increase in hepatic drug-metabolizing enzyme expression in 3-week-old female mice that persisted into 8-week-old adulthood. Interestingly, we observed distorted intestinal morphological features in 8-week-old F1 female mice in the TC-exposed group. Moreover, maternal TC exposure triggered a loss of intestinal barrier integrity by reducing the expression of intestinal tight junction proteins. Accordingly, maternal exposure to TC down-regulated serum triglyceride levels as well as decreased the expression of intestinal lipid uptake and transport marker genes. Mechanistically, maternal TC exposure activated the intestinal inflammatory response and disrupted the antioxidant system in the offspring female mice, thereby impeding the intestinal absorption of nutrients and seriously threatening offspring health. Altogether, these findings highlight that the effects of maternal TC exposure on offspring toxicity could not be ignored.
引用
收藏
页数:19
相关论文
共 30 条
  • [1] Off-target lipid metabolism disruption by the mouse constitutive androstane receptor ligand TCPOBOP in humanized mice
    Skoda, Josef
    Dohnalova, Klara
    Chalupsky, Karel
    Stahl, Aaron
    Templin, Markus
    Maixnerova, Jana
    Micuda, Stanislav
    Grontved, Lars
    Braeuning, Albert
    Pavek, Petr
    BIOCHEMICAL PHARMACOLOGY, 2022, 197
  • [2] Environmental chemical TCPOBOP exposure alters milk liposomes and offspring growth trajectories in mice
    Pan, Shijia
    Yu, Wen
    Zhang, Jia
    Guo, Yuan
    Qiao, Xiaoxiao
    Xu, Pengfei
    Zhai, Yonggong
    ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY, 2024, 272
  • [3] Constitutive androstane receptor agonist, TCPOBOP,attenuates steatohepatitis in the methionine choline-deficientdiet-fed mouse
    Edwina S Baskin-Bey
    Akira Anan
    Hajime Isomoto
    Steven F Bronk
    Gregory J Gores
    World Journal of Gastroenterology, 2007, (42) : 5635 - 5641
  • [4] Effects of Absence of Constitutive Androstane Receptor (CAR) on Bile Acid Homeostasis in Male and Female Mice
    Lickteig, Andrew J.
    Zhang, Youcai
    Klaassen, Curtis D.
    Csanaky, Ivan L.
    TOXICOLOGICAL SCIENCES, 2019, 171 (01) : 132 - 145
  • [5] Constitutive androstane receptor agonist, TCPOBOP, attenuates steatohepatitis in the methionine choline-deficient diet-fed mouse
    Baskin-Bey, Edwina S.
    Anan, Akira
    Isomoto, Hajime
    Bronk, Steven F.
    Gores, Gregory J.
    WORLD JOURNAL OF GASTROENTEROLOGY, 2007, 13 (42) : 5635 - 5641
  • [6] Constitutive androstane receptor agonist CITCO inhibits growth and expansion of brain tumour stem cells
    Chakraborty, S.
    Kanakasabai, S.
    Bright, J. J.
    BRITISH JOURNAL OF CANCER, 2011, 104 (03) : 448 - 459
  • [7] A crucial role of constitutive androstane receptor (CAR) in liver tumor development by imazalil in mice
    Tamura, Kei
    Inoue, Kaoru
    Takahashi, Miwa
    Matsuo, Saori
    Kodama, Yukio
    Yoshida, Midori
    JOURNAL OF TOXICOLOGICAL SCIENCES, 2016, 41 (06) : 801 - 811
  • [8] Maternal Benzophenone Exposure Impairs Hippocampus Development and Cognitive Function in Mouse Offspring
    Cui, Fengzhen
    Pan, Qingfei
    Wang, Siyi
    Zhao, Faming
    Wang, Runxin
    Zhang, Tingting
    Song, Yaying
    He, Jun
    Zhang, Haolin
    Weng, Qiang
    Jin, Yang
    Xia, Wei
    Li, Yuanyuan
    Yang, Guo-Yuan
    De Vos, Winnok H.
    Timmermans, Jean-Pierre
    Xu, Shunqing
    Tang, Yaohui
    Sheng, Xia
    ADVANCED SCIENCE, 2021, 8 (23)
  • [9] Disrupted serotonin system development via early life antidepressant exposure impairs maternal care and increases serotonin receptor expression in adult female offspring
    Unroe, Keaton A.
    Maltman, Jessica L.
    Shupe, Elizabeth A.
    Clinton, Sarah M.
    DEVELOPMENTAL PSYCHOBIOLOGY, 2022, 64 (06)
  • [10] Maternal Smoke Exposure Impairs the Long-Term Fertility of Female Offspring in a Murine Model
    Camlin, Nicole J.
    Sobinoff, Alexander P.
    Sutherland, Jessie M.
    Beckett, Emma L.
    Jarnicki, Andrew G.
    Vanders, Rebecca L.
    Hansbro, Philip M.
    McLaughlin, Eileen A.
    Holt, Janet E.
    BIOLOGY OF REPRODUCTION, 2016, 94 (02)