Mitochondrial dysfunction in early life resulted from perinatal bisphenol A exposure contributes to hepatic steatosis in rat offspring.
An emerging literature suggests that bisphenol A (BPA), a widespread endocrine disrupting chemical, when exposure occurs in early life, may increase the risk of metabolic syndrome. In this study, we investigated the hypothesis that perinatal exposure to BPA predisposed offspring to fatty liver disease: the hepatic manifestation of metabolic syndrome, and its possible mechanism. Pregnant Wistar rats were administered with BPA (40μg/kg/day) or vehicle during gestation and lactation. Liver histology, biochemical analysis, transcriptome, and mitochondrial function were examined in male offspring at postnatal 3, 15 and 26 weeks. At 3 weeks of age, abnormal liver morphology and function were not observed in the BPA-exposed offspring, but a decrease in mitochondrial respiratory complex (MRC) activity (I and III) and significant changes in gene expression involved in mitochondrial fatty acid metabolism were observed compared with controls. At 15 weeks, micro-vesicular steatosis in liver, up-regulated genes involved in lipogenesis pathways, increased ROS generation and Cytc release were observed in the BPA-exposed offspring. Then, extensive fatty accumulation in liver and elevated serum ALT were observed in BPA-exposed offspring at 26 weeks. In the longitudinal observation, hepatic mitochondrial function including MRC activity, ATP production, ROS generation and mitochondrial membrane potential were progressively worsened in the BPA-exposed offspring. Perinatal BPA exposure contributes to the development of hepatic steatosis in the offspring of rats, which may be mediated through impaired hepatic mitochondrial function and up-regulated hepatic lipid metabolism.
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Ying
Y
Jiang
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Wei
W
Xia
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Yingshuang
Y
Zhu
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Xiaocui
X
Li
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Danqi
D
Wang
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Juan
J
Liu
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Huailong
H
Chang
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Gengqi
G
Li
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Bing
B
Xu
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Xi
X
Chen
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: liyuanyuan@hust.edu.cn.
Yuanyuan
Y
Li
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: xust@hust.edu.cn.
Shunqing
S
Xu
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001559:Benzhydryl Compounds / Q000009:adverse effects*; D015153:Blotting, Western; D001835:Body Weight; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005234:Fatty Liver / Q000139:chemically induced* / Q000473:pathology; D005260:Female; D022781:Hepatocytes / Q000378:metabolism; D008055:Lipids / Q000096:biosynthesis; D008099:Liver / Q000473:pathology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D028361:Mitochondrial Diseases / Q000139:chemically induced* / Q000473:pathology; D010636:Phenols / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014280:Triglycerides / Q000097:blood; D000098826:Bisphenol A Compounds
D000255:Adenosine Triphosphate; D001559:Benzhydryl Compounds; D045304:Cytochromes c; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D010636:Phenols; D017382:Reactive Oxygen Species; D014280:Triglycerides; C006780:bisphenol A; D000098826:Bisphenol A Compounds
Bisphenol A; Early-life; Mitochondria dysfunction; Nonalcoholic fatty liver disease; Reactive oxygen species