Objective To investigate the effect of quercetin (Que) administration during pregnancy on bisphenol A (BPA)-induced hepatic lipid accumulation in littermates and its mechanism. Methods Fifteen female SD rats (12 w) were randomly divided into three groups: control group (saline gavage), BPA [1 μg/(kg·d) BPA solution by gavage], and BPA+Que group [1 μg/(kg·d) BPA solution + 120 mg/(kg·d) quercetin solution by gavage]. Mothers were treated by gavage separately from two weeks before conception, and the intervention was continued until the end of lactation (3 w after delivery). The sex of the offspring was identified, and the body weight of the female and male offspring was measured every 1 day during the experiment. After weaning, the male offspring were anesthetized and killed, and the serum and liver tissues were collected, and Western blot was used to detect adenosine 5'-monophosphate-activated protein kinase (AMPK), sterol-regulatory element binding protein 1 (SREBP1), fatty acid synthase (FAS), and fatty acid synthase (FAS). AMPK- SREBP1- FAS/acetyl-coenzyme A carboxylase (ACC) were detected by Western blot. The expression of AMPK, SREBP1, FAS and ACC mRNA was detected by q-PCR. Results Compared with the control group, the offspring male rats in the BPA group had a significant increase in body weight at the 17th d of birth, and the offspring rats had a significant increase in liver weight, liver-to-body ratio, and serum ALT, AST, TC, and TG contents (P<0.05). Compared with the BPA group, the BPA+Que group had a decrease in body weight at the 7th d, and in the third week after weaning, the BPA+Que group had a decrease in liver weight, liver-to-body ratio, and serum ALT, AST, TG, and TC contents (P<0.05). Compared with the control group, the oil red O staining in the BPA group showed an increase in the number of lipid droplets in the liver tissues of the offspring male rats. The HE staining showed an increase in the number of fat vacuoles in the hepatocytes of the offspring male rats, while the accumulation of lipid droplets as well as fat vacuoles was reduced in the BPA+Que group compared with the BPA group after quercetin treatment. Western blot and q-PCR results showed that exposure to BPA during pregnancy resulted in decreased expression of p-AMPK/AMPK protein and AMPK mRNA and increased expression of SREBP1, FAS, and ACC proteins and mRNA in the BPA group compared to the control group (P<0.05). Quercetin up-regulated the expression of p-AMPK/AMPK protein and AMPK mRNA in the livers of offspring male rats compared to the BPA group, while reversing the up-regulated levels of SREBP1, FAS, ACC protein and mRNA (P<0.05). Conclusion Low-dose BPA exposure during pregnancy and lactation resulted in body weight gain and increased expression of fat synthesis-related regulatory factors in offspring male rats, and quercetin ameliorated BPA-induced hepatic lipid accumulation. It provides an important implication for exploring the prevention of the hepatic lipid accumulation in the offspring by quercetin in response to prenatal BPA exposure.
Key words
bisphenol A /
quercetin /
liver lipid accumulation /
male rat offspring
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