Effective Mechanism Of Quercetin On Polychlorinated Biphenyls Induced Implantation Dysfunction

Polychlorinated biphenyls (PCBs) are widespread persistent residual environmentalpollutants. As environmental endocrine regulator, PCBs can affect synthesis, secretion,combination and metabolic process of the body by simulating natural hormones orinterfering with the natural hormones, cause damage or toxicity to the target organs, reducethe sensitivity of the target organs to the natural hormone, affect the endocrine function ofanimal, and seriously interfere the growth and development, reproductive function ofanimals. PCBs adversely affect fertilization and cause degeneration of oocytes andabnormality in the early embryo. In this paper, the injured hepatocytes and endometrialcells implantation dysfunction models in the pregnant rats are prepared by typicaldioxin-like polychlorinated biphenyls Aroclor1254induction, the models are treated withquercetin, so as to study the effective mechanism of quercetin on Aroclor1254inducedimplantation dysfunction, to provide a basis on herbal medicine protection for animalreproductive diseases caused by environmental endocrine disruptors.1. Experiments in vitro: The hepatocytes and endometrial cells in the pregnant rats areisolated and cultured, by MTT method,10μg/mL Aroclor1254was the optimalconcentration for inducing the endometrial cells injured model. By RT-PCR, Western blot,and ELISA methods, it showed that the injured hepatocytes swelled, less cytoplasm, evenvacuoles appeared, the profile of some cells was vague. The contents of TNF-α and IL-6increased significantly (P＜0.05); the configuration of the injured hepatocytes turned tonormal with the treatment of10μmol/L quercetin, the expressions of CYP1A1, CYP2B1,and CYP2E1increased gradually with the treatment of the gradient quercetin, the contentsof TNF-α and IL-6decreased significantly (P＜0.05). The injured endometrial cells shrank,some cells swelled or showed less cytoplasm, even the vacuoles appeared inside theendometrial cells, the contents of TNF-α, IL-6, and E2increased and P4decreasedsignificantly (P＜0.05); the configuration of the injured endometrial cells turned to normalwith the treatment of50μmol/L quercetin at24h, the expression of CYP2B1increasedgradually, the contents of TNF-α, IL-6, and E2decreased and P4increased significantly (P＜0.05).2. Experiments in vivo:(1) The rats administered intragastrically the gradient Aroclor1254at days4to7ofgestation, RT-PCR and Western blot analyses were performed to determine the expression levels of CYP1A1, CYP2B1, and CYP2E1. ELISA was used to detect TNF-α, IFN-γ, IL-2,IL-4, IL-6, E2,and P4,the morphology of the liver and uterus was observed under amicroscope. It found that the rate of embryo implantation decreased with the treatment ofgradient Aroclor1254, the ratio of embryo in the development delay and degenerationincreased (P＜0.05). The expression levels of CYP1A1, CYP2B1, and CYP2E1increasedwith the treatment of gradient Aroclor1254. The contents of TNF-α, IFN-γ, IL-2, and IL-6in the livers, uterus, and serum increased, and IL-4decreased significantly (P＜0.05). Thepathomorphology of liver and uterus tissue changed obviously: The hepatic cord damageby Aroclor1254was demonstrated by disorganization, swollen cell parts, decreasedcytoplasm, and the appearance of vacuoles; uterine wall thickening, smooth muscle cellsarranged in spiral shape, uterus glandular epithelial cells appeared vacuolated.1mg/100gBW Aroclor1254was the optimal concentration to establish the embryo implantationdysfunction model.(2)The rats at days4to7of gestation were adminisered Que orally, the rate of embryoimplantation increased with the treatment of gradient Que, the ratio of embryo in thedevelopment delay and degeneration decreased. The expression levels of CYP1A1,CYP2B1, and CYP2E1decreased significantly with the treatment of15mg/100g BW Quein the liver and uterus, there were no changement in other groups. The contents of TNF-α,IFN-γ, IL-2, and IL-6in the liver, uterus, and serum decreased, IL-4increased significantly(P＜0.05). The pathomorphology of liver and uterus tissue tended to normalize. Thehepatic cord arranged radially at the center of the central vein, the profile was clear, thenumber of vacuoles decreased significantly. The endometrium was integrated, intimalthickening, the number of glands increased (P＜0.05). The number of CD4+T celldecreased (P＜0.05)，Que led to a Th2dominant shift in uterusIn conclusion, Aroclor1254can cause rat liver cells and endometrial cells damaged, andpregnant rat embryo implantation dysfunction. Quercetin can antagonize Aroclor1254caused damage, repair the injured liver, improve the uterus immune balance, and regulatethe hormone secretion in animal body.