Lalitkumar P G L, Lalitkumar S, Meng C X, Stavreus-Evers A, Hambiliki F, Bentin-Ley U, Gemzell-Danielsson Kristina
Division of Obstetrics and Gynecology, Department of Woman and Child Health, Karolinska Institutet, Karolinska University Hospital, S-171 76, Stockholm, Sweden.
Hum Reprod. 2007 Nov;22(11):3031-7. doi: 10.1093/humrep/dem297. Epub 2007 Sep 21.
The use of fertility regulating drugs is limited among various socio-ethnic groups due to limited knowledge about their mechanism of action. This study investigates the effect of levonorgestrel and mifepristone on attachment of human embryos to an in vitro endometrial construct.
Three-dimensional endometrial constructs were established by co-culturing early luteal phase human endometrial stromal and epithelial cells. Expression of endometrial receptivity markers in this construct were examined by immunohistochemistry. Effects of mifepristone and levonorgestrel on viability and attachment of human blastocysts were investigated.
Endometrial constructs expressed the factors involved in endometrial receptivity: estrogen receptor, progesterone receptor, vascular endothelial growth factor, leukemia inhibitory factor, interleukin-1, COX-2, MUC-1 and integrin-alpha(V)beta(3). None of the 15 embryos cultured with mifepristone attached to the endometrial construct (P < 0.01), whereas 10/17 in control, and 6/14 in levonorgestrel, groups attached. The attachment was confirmed by the positive expression of cytokeratin 7 at the attachment site.
Mifepristone inhibits blastocyst attachment. Levonorgestrel did not impair the attachment of human embryos to the in vitro endometrial construct. This model could be used to understand endometrial receptivity and embryo-endometrial dialog and to develop new fertility regulating substances.
由于对生育调节药物作用机制的了解有限，其在不同社会种族群体中的使用受到限制。本研究调查左炔诺孕酮和米非司酮对人胚胎附着于体外子宫内膜构建体的影响。
通过共培养黄体早期人子宫内膜基质细胞和上皮细胞建立三维子宫内膜构建体。通过免疫组织化学检查该构建体中子宫内膜容受性标志物的表达。研究米非司酮和左炔诺孕酮对人囊胚活力和附着的影响。
子宫内膜构建体表达参与子宫内膜容受性的因子：雌激素受体、孕激素受体、血管内皮生长因子、白血病抑制因子、白细胞介素 -1、COX -2、MUC -1和整合素α(V)β(3)。用米非司酮培养的15个胚胎中无一附着于子宫内膜构建体（P < 0.01），而对照组17个中有10个附着，左炔诺孕酮组14个中有6个附着。通过附着部位细胞角蛋白7的阳性表达证实了附着。
米非司酮抑制囊胚附着。左炔诺孕酮不损害人胚胎附着于体外子宫内膜构建体。该模型可用于理解子宫内膜容受性以及胚胎 - 子宫内膜对话，并开发新的生育调节物质。
