| Widely used in various fields related to human lives, perfluorooctane acid(PFOA) is considered to be one of the persistent organic pollutants. Recently, the toxicity of PFOA to the liver and reproductive system to humans and animals has aroused highly attention. As one of the natural carotenoids, Lycopene has super antioxidant capacity, but also has the ability to protect liver and kidney from damage, anti-tumor, enhance immunity, and many other effects. This study, divided into three parts, was designed to investigate the toxic effects and mechanisms of PFOA to the liver and uterus of pregnant mice and mitigative effect of lycopene.First, toxic effect of PFOA on the uterus and liver of the mouse during early pregnancy. Pregnant 0 d mice were divided into six groups randomly, each group of 10. Group A was the control group, mice in group A were gavaged with 10 mg/kg of distilled water, other groups were given 1, 5, 10, 20, 40 mg/kg PFOA(distilled water as the solvent) by gavage respectively. All mice were gavaged on gestational day 1-7, and sacrificed on day 9. Body weight of each mouse was monitored during the experiment. Liver index, uterine index, average uterine weight and average number of embryo implantation were counted; histopathological changes of the liver and uterus were observed by preparing paraffin sections and HE staining; superoxide dismutase(SOD), glutathione peroxidase(GSH-Px) and malondialdehyde(MDA), in liver were detected by spectrophotometric method. Results showed that 20, 40 mg/kg PFOA exposed to pregnant mice led to weight loss; the liver index of PFOA treated groups were significantly increased dose-dependently; significant pathological changes were observed in the liver; with increasing doses of PFOA, SOD and GSH-Px were significantly decreased, and MDA increased significantly in liver tissue; abortion or embryonic absorption happened to mice in the 40 mg/kg group, with significant pathological changes; uterus index, average uterine weight and average number of embryo implantation in the uterus were reduced significantly at 40mg/kg compared to the controls. The results in this part suggested that oxidative damage may be one of the mechanism liver toxicity and exposed to high dose of PFOA during early pregnancy may lead to congestion and embryo resorption.Second, reproductive toxicity of PFOA in mice during late pregnancy. Pregnant 0 d mice were divided into six groups randomly, each group of 10. Group A was the control group, mice in group A were gavaged with 10 mg/kg of distilled water, other groups were given 1, 5, 10, 20, 40 mg/kg PFOA by gavage respectively. All mice were gavaged on gestational day 1-17, and sacrificed on day 18. Body weights of the maternal were recorded everyday. Liver index, uterine index, average weight of the uterine and fetus were counted; expression of Fas, Fas L, Bax, Bcl-2 and Caspase-3 in uterine cells by the method of immunohistochemistry were detected; apoptosis of cells in the uterus were detected with the method of TUNEL. As is shown in the results, in the 1, 5 mg/kg PFOA groups and the control group body weight of the maternals increased continuously, in the 10, 20 mg/kg PFOA groups body weight of pregnant mice showed a slow upward trend, while in the 40 mg/kg group, all embryos were aborted, leading to the maternal weight decreased; the PFOA exposed groups increased liver index significantly and decreased uterine index, average weight of the uterine and fetus significantly except 1 mg/kg group; moreover, PFOA up-regulated expression of Fas, Fas L, Bax and Caspase-3, down-regulated the expression of Bcl-2, and reduced the ratio of Bcl-2/Bax dose-dependently; PFOA increased the number of apoptotic cells in uterus, dose-dependently. It is suggested that PFOA could up-regulate expression of Fas, Fas L, Bax and Caspase-3, and down-regulate expression of Bcl-2 in uterine cells, leading to excessive apoptosis of uterine cells, this may induce embryo loss and a slow embryonic development.Last, mitigation effect of lycopene on PFOA-induced liver and uterine damage. Pregnant 0 d mice were randomly divided into 5 groups, each group of 10. Group A was the control group, mice in group A were given soybean oil every morning on gestational day 1-8, 0.1 m L for each, and 10 mg/kg of distilled water by gavage in the afternoon of gestational day 1-7; group B was the PFOA-treated group, pregnant mice were given soybean oil in the morning of gestational day 1-8, 0.1 m L for each, and 20 mg/kg of PFOA in the afternoon of gestational day 1-7; group C for a low dose of lycopene(10 mg/kg), group D for a moderate dose of lycopene(20 mg/kg), group E for a high dose of lycopene(40 mg/kg), mice in group C, D and E were given lycopene every morning on gestational day 1-8, 0.1 m L for each, and 20 mg/kg of PFOA in the afternoon of gestational day 1-7. The maternal body weight was monitored everyday, and all mice were sacrificed on gestational day 9. Liver index was counted, and 0.2 g liver tissue were collected to prepare liver homogenates for the detecting of SOD, GSH-Px and MDA; intact uterus was removed, uterine index and average uterine weight were recorded. The results showed that lycopene relieved the decrease trend of mater weight; high dose of lycopene decreased liver index significantly; moderate dose and high dose of lycopene increased uterine index, average weight of uterus significantly; high dose of lycopene significantly improved contents of SOD and GSH-Px compared with the PFOA-treated group; all lycopene groups decreased MDA level significantly, and had no significant difference with the control group. Results of this part suggested that lycopene could improve the antioxidant capacity of the liver, and this may be one of the mechanisms of lycopene to protect liver from damage by PFOA.The results showed that continuous exposed to PFOA during early pregnancy could cause significant liver toxicity, in a dose-dependent manner, characterized by increased liver index, obvious pathological changes in liver, decreased enzyme activity of SOD and GAH-PX, and increased content of MDA. Exposed to high dose of PFOA lead to abortion in early pregnancy, and continuous exposed to PFOA could cause embryo lost and slow growth of the fetus during pregnancy. PFOA up-regulated the expression of Fas, Fas L, Bax and Caspase-3 in uterus, and down-regulated the expression of Bcl-2, leading to excessive apoptosis of uterine cells, dose-dependently. Lycopene alleviated the the toxic effects of PFOA on liver and uterus of pregnant mice, effectively improved SOD and GSH-Px enzyme activity, and decreased MDA level, thus, lycopene has the effect of protecting liver. |
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