Perfluorooctanoic acid exposure in early pregnancy induces oxidative stress in mice uterus and liver

Zhang, Yan; Zhang, Linchao; Bao, Jialu; Liu, Liantao; Wang, Xiaodan

Perfluorooctanoic acid exposure in early pregnancy induces oxidative stress in mice uterus and liver

2021

Zhang, Yan | Zhang, Linchao | Bao, Jialu | Liu, Liantao | Wang, Xiaodan

This study aimed to explore the mechanism of perfluorooctanoic acid (PFOA) toxicity on the uterus and liver of mice during early pregnancy. Pregnant mice were given 0, 1, 5, 10, 20, and 40 mg/kg PFOA daily by gavage from gestational day (GD) 1–7 and sacrificed on GD 9. Subsequently, several toxicity parameters were evaluated, including the uterus and liver weights, liver and uterine indexes, histopathological changes of the liver and uterus, and levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in the liver. We also determined the expressions of FAS, FASL, Bax, Bcl-2, and Caspase-3 in decidual cells by immunohistochemistry and the TUNEL assay to detect apoptosis uterine cells. The results showed that PFOA increased the liver weights and reduced the uterus index in a dose-dependent manner. With increasing doses of PFOA, the levels of SOD and GSH-Px were significantly decreased, and MDA increased substantially in liver tissue. 20 mg/kg and 40 mg/kg of PFOA caused more substantial harm to the uterus, thus a higher probability for congestion and resorption. The expression of FAS, FASL, Bax, and Caspase-3 in decidual cells of the uterus in the PFOA treatment groups significantly increased in a dose-dependent manner. The expression of Bcl-2 was downregulated, decreasing the Bcl-2/Bax ratio. At gestation day 9, the control group had significantly fewer apoptotic cells in the uterus and shallower staining than the 40 mg/kg PFOA group. The findings of this study suggest that oxidative damage may be one of the mechanisms by which PFOA induces liver toxicity, and a subsequent increase in uterine cell apoptosis may cause embryo loss or damage.

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