戊酸雌二醇对胚胎着床障碍小鼠子宫内膜容受性的调节作用

Regulation of Estradiol Valerate on Endometrial Receptivity in Mice with Embryonic Implantation Dysfunction

目的探讨戊酸雌二醇对胚胎着床障碍小鼠子宫内膜容受性相关分子的调节作用。方法将雌性KM小鼠随机分为阴性对照组、模型组和戊酸雌二醇组，每组33只，建立肾虚胚胎着床障碍小鼠模型，同时戊酸雌二醇组灌胃给予剂量0．2mg＆g体质量戊酸雌二醇，阴性对照组和模型组灌胃给予相同剂量生理盐水，于妊娠第4日上午9点、晚上21点、晚上23点处死小鼠取子宫，分别采用电镜扫描法检测子宫内膜胞饮突、免疫组化方法检测MMP．9、TIMP．3、基质内膜腔上皮和基质细胞的环氧化酶-2（cox-2）、子宫组织前列腺素12（prostaglandin12，POh）的表达。结果模型组子宫内膜表面胞饮突的发育不同步，或大小不一。戊酸雌二醇组子宫内膜表面分布着大量的膜状突起，从形态上看发育略迟后于阴性对照组。模型组与阴性对照组的子宫内膜腺上皮细胞、腔上皮细胞中COX-2和PG12蛋白、MMP-9蛋白表达有显著性差异（P〈0．05）；模型组与阴性对照组的子宫内膜腺上皮细胞、腔上皮细胞中TIMP-3蛋白的表达有显著性差异（Ｐ〈0．01）；戊酸雌二醇组可显著升高子宫内膜COX-2和PG12蛋白、TIMP-3和MMP-9蛋白的表达（P〈O．05）。结论戊酸雌二醇具有改善胚胎着床障碍的作用，可能是通过间接促进胚胎着床障碍小鼠子宫内膜胞饮突的形成，子宫内膜中COX-2和PG12蛋白、TIMP-3和MMP-9蛋白的表达升高，建立子宫内膜容受性状态，从而改善胚胎着床障碍的作用。

Objective To investigate the regulation of estradiol valerate on endometrial receptivity in mice with embryonic implantation dysfunction. Methods The female KM mice were randomized into negative control group,model group and estradiol valerate group ,with 33 mice for each group, to build embryo implantation dysfunction mouse model. Mice in estradiol valerate group were administrated by gastric perfusion of 0.2mg/kg estradiol valerate and mice in negative control group and model group was given by the same dose saline. Mice were sacrificed individually at 9 ： 00, 21：00 and 23 ： 00 in the 4th day after gestation, and uterus were taken out for detecting pinopode by scanning electron microscopy and the expression of MMP-9,TIMP-3,COX-2 and PGI2 by immunohistochemistry. Results The pinopode of endometrium in negative control group was uniform distribution,significantly more prominent than processes on the surface of membrane,with almost same size and clear boundaries, which was the developing pinopode. The pinopode of endometrium in model group was reversible focal expression, with asynchronized development of pinopode, or the inconsistent size of pinopode. There were a large number processes in endometrium with inconsistent size, slightly lower than that in the negative control group：short and thin microvilli on the surface of processes also was the developing pinopode,slightly later development lagged behind than that in the negative control group on morphology. There was significant difference between the model group and negative control group by the expression of COX-2, PGL and MMP-9 protein, protein of endometrial glandular epithelial cells and luminal epithelial cells （P〈0.05）, comparing with the negative control group, the expression of TIMP-3 protein in endometrial glandular epithelial cells and luminal epithelial cells had significant difference in the model group （P〈0.01）, valerate estradiol significantly increased the expression of COX-2, PGI2, TIMP-3 and MMP-9 protein in the endometrium （P〈0.05）. Conclusion Estradiol valerate could improve embryo implantation and it may works by indirectly promoting of pinopode formation in mice with embryonic implantation dysfunction, increasing of the expression of COX-2, PGI2, TIMP-3 and MMP-9 in endometrium, and establishing endometrial receptivity, for improving embryo implantation dysfunction of mice.