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.
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页数:19
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