Maternal exposure to perfluorooctanoic acid (PFOA) causes liver toxicity through PPAR-α pathway and lowered histone acetylation in female offspring mice

2019 ◽  
Vol 26 (18) ◽  
pp. 18866-18875 ◽  
Author(s):  
Danyang Li ◽  
Linchao Zhang ◽  
Yan Zhang ◽  
Shuo Guan ◽  
Xincheng Gong ◽  
...  
2021 ◽  
Author(s):  
Yan Zhang ◽  
Linchao Zhang ◽  
JiaLu Bao ◽  
LianTao Liu ◽  
Xiaodan Wang

Abstract To investigate the mechanism perfluorooctanoic acid (PFOA)’s toxicity on the uterus and liver of the mice during early pregnancy, pregnant mice were given 0, 1, 5, 10, 20, 40 mg/kg PFOA daily by gavage from gestational day (GD) 1-7, and sacrificed on GD 9. Uterus and liver weight were recorded, liver and uterine indexes were calculated, histopathological changes of the liver and uterus were examined, and levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) in liver were detected by spectrophotometric method. Expression of FAS, FASL, Bax, Bcl-2, and Caspase-3 in decidual cells were detected by immunohistochemistry and the TUNEL method was used to detect apoptotic uterine cells. Results showed that liver weight increased, and the uterus index was significantly reduced at 40 mg/kg compared with the control group. With increasing doses of PFOA, levels of SOD and GSH-PX were significantly decreased, and MDA significantly increased in liver tissue. 20 mg/kg and 40 mg/kg of PFOA caused greater harm to the uterus and congestion and resorption may occur. Expression of FAS, FASL, Bax, and Caspase-3 in decidual cells of the uterus in PFOA treatment groups significantly increased in a dose-dependent manner. The expression of Bcl-2 was down-regulated, which decreased the ratio of Bcl-2/Bax. It is therefore proposed that oxidative damage may be one of the mechanisms by which PFOA induces liver toxicity, and a subsequent increase in uterine cell apoptosis may induce embryo loss or damage.


2010 ◽  
Vol 21 (4) ◽  
pp. 283-291 ◽  
Author(s):  
Chengjun Yu ◽  
Fadao Tai ◽  
Ruiyong Wu ◽  
Zhenzhen Song ◽  
Xia Zhang ◽  
...  

2020 ◽  
Vol 94 ◽  
pp. 84-91
Author(s):  
Ryan Gillies ◽  
Kendrick Lee ◽  
Sebastian Vanin ◽  
Steven R. Laviolette ◽  
Alison C. Holloway ◽  
...  

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Josephine Bou Dagher ◽  
Maryam Al Mansi ◽  
Amrita Kaimal ◽  
Katarzyna Rzepka ◽  
Kryzystof Czaja ◽  
...  

2010 ◽  
Vol 30 (2) ◽  
pp. 216-224 ◽  
Author(s):  
Emilija Makaji ◽  
Shirley H. Y. Ho ◽  
Alison C. Holloway ◽  
Denis J. Crankshaw

The goal of our study was to determine whether maternal exposure to red raspberry leaf (RRL) and its constituents can permanently alter biotransformation of fluorogenic substrates by cytochrome P450 (CYP) in the livers of male and female offspring. Nulliparous female rats received vehicle, raspberry leaf, kaempferol, quercetin, or ellagic acid orally once breeding had been confirmed until parturition. Hepatic microsomes were prepared from animals at birth (postnatal day 1 [PND1]), weaning (PND21), PND65, and PND120 to determine the biotransformation of 8 fluorogenic substrates. The pattern of biotransformation of all but 2 of the substrates was gender specific. Maternal consumption of RRL increased biotransformation of 3 substrates by female offspring at PND120 resulting in a more masculine profile. Kaempferol and quercetin had a similar effect to RRL. These results suggest that maternal consumption of either RRL or some of its constituents leads to long-term alterations of CYP activity in female offspring.


2018 ◽  
Vol 9 (11) ◽  
pp. 5768-5777 ◽  
Author(s):  
Jiaomei Li ◽  
Kelei Li ◽  
Jinlong Gao ◽  
Xiaofei Guo ◽  
Mengqing Lu ◽  
...  

Maternal exposure to n-3 PUFAs has a protective effect on mammary tumor risk of female offspring in later life by influencing epigenetics.


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