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目的建立双酚A(BPA)暴露的昆明雌鼠动物模型,研究暴露后子宫内膜胞饮突的形态学改变以及HOXA-10基因在mRNA水平和蛋白水平表达的改变,探讨BPA对子宫内膜容受性的影响及可能机制。方法将昆明雌鼠随机分成4组:高剂量暴露组、中剂量暴露组、低剂量暴露组和空白对照组。每组以花生油为溶剂,分别按250 mg/(kg·d),50 mg/(kg·d),10 mg/(kg·d),0 mg/(kg·d)进行BPA灌胃染毒,共28 d,第29天腹腔注射人绝经期促性腺激素(HMG)7.5 IU,48 h后腹腔注射h CG 10 IU,于当晚雌雄昆明小鼠1∶1合笼,次日可见阴道栓者为孕0 d,孕5 d后断椎处死,取出子宫,采用扫描电镜观察子宫内膜表面的胞饮突的形态学表现,应用Western Blot、免疫组化和荧光定量PCR测定HOXA-10的表达情况。结果扫描电镜结果提示,各剂量BPA干预组着床期胞饮突的数目均比对照组少,分布松散且不均,形态不一。HE染色显示,BPA干预组子宫宫腔均较对照组大,子宫内膜上皮细胞的高度较低,排列紧密,间质细胞连接紧密,腺体数量较少。荧光定量PCR、免疫组化和Western Blot结果提示,BPA干预组HOXA-10基因在mRNA及蛋白水平的表达量均较对照组降低(P<0.05)。结论通过对昆明雌鼠进行BPA的慢性暴露发现,BPA对小鼠胚胎着床期胞饮突的形成表现为抑制作用,同时抑制HOXA-10基因的表达。BPA可能通过改变子宫内膜容受性干扰胚胎着床。
OBJECTIVE: To establish animal model of Kunming female rats exposed to BPA and study the morphological changes of endometriosis and the expression of HOXA-10 mRNA and protein in the exposed endometrium. Tolerance and possible mechanisms. Methods Kunming female rats were randomly divided into 4 groups: high dose exposure group, medium dose exposure group, low dose exposure group and blank control group. The rats in each group were treated with 250 mg / (kg · d), 50 mg / (kg · d), 10 mg / (kg · d) and 0 mg / (kg · d) of peanut oil for intragastric administration , A total of 28 days, the first 29 days of human menopause gonadotropin (HMG) 7.5 IU, 48 h after intraperitoneal injection of h CG 10 IU, that male and female Kunming mice that day 1: 1 cage, the next day visible vaginal suppository For 0 d, 5 d after pregnancy, the vertebrae were sacrificed and the uterus was taken out. Morphology of the pinopodes on the endometrium was observed by scanning electron microscopy. The expression of HOXA-10 was detected by Western Blot, immunohistochemistry and real-time PCR Happening. Results The results of scanning electron microscopy suggested that the numbers of pinopodes in each dose of BPA intervention group were less than those in control group, with loose distribution and uneven distribution. HE staining showed that the uterine cavity in the BPA intervention group was larger than that in the control group, the height of the endometrial epithelial cells was lower, the arrangement was close, the interstitial cells were closely connected, and the number of glands was less. Fluorescent quantitative PCR, immunohistochemistry and Western Blot suggested that HOXA-10 mRNA and protein levels in BPA intervention group were significantly lower than those in control group (P <0.05). Conclusion The chronic exposure of BPA to Kunming female rats showed that BPA could inhibit the formation of the pinopodes and inhibit the expression of HOXA-10 gene. BPA may interfere with embryo implantation by altering endometrial receptivity.