In vitro fertilization has overcome infertility issues for many couples. However, achieving implantation of a viable embryo into the maternal endometrium remains a limiting step in optimizing pregnancy success. The molecular mechanisms which characterize the transient state of endometrial receptivity, critical in enabling embryo-endometrial interactions, and proteins which underpin adhesion at the implantation interface, are limited in humans despite these temporally regulated processes fundamental to life. Hence, failure of implantation remains the "final frontier" in infertility. A human coculture model is utilized utilizing spheroids of a trophectoderm (trophoblast stem) cell line, derived from pre-implantation human embryos, and primary human endometrial epithelial cells, to functionally identify "fertile" versus "infertile" endometrial epithelium based on adhesion between these cell types. Quantitative proteomics identified proteins associated with human endometrial epithelial receptivity ("epithelial receptome") and trophectoderm adhesion ("adhesome"). As validation, key "epithelial receptome" proteins (MAGT-1/CDA/LGMN/KYNU/PC4) localized to the epithelium of receptive phase (mid-secretory) endometrium obtained from fertile, normally cycling women but is largely absent from non-receptive (proliferative) phase tissues. Factors involved in embryo-epithelium interaction in successive temporal stages of endometrial receptivity and implantation are demonstrated and potential targets for improving fertility are provided, enhancing potential to become pregnant either naturally or in a clinical setting.

中文翻译：

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蛋白质组学对子宫内膜容受性和胚胎-子宫内膜上皮相互作用的植入揭示了生育力的关键决定因素。

体外受精已经克服了许多夫妻的不育问题。然而，实现将可行的胚胎植入母体子宫内膜仍然是优化妊娠成功的限制步骤。尽管这些对生命至关重要的时间调控过程，但在人类中，表征子宫内膜接受性瞬态状态的分子机制（在实现胚胎与子宫内膜相互作用中起关键作用的蛋白质）以及在植入界面处支持粘附的蛋白质受到限制。因此，植入失败仍然是不孕症的“最后领域”。利用人类共培养模型，利用来自植入前人类胚胎和原代人子宫内膜上皮细胞的滋养外胚层（滋养细胞干）细胞系的球状体，从功能上识别“受精”与“可育” 子宫内膜上皮基于这些细胞类型之间的粘附。定量蛋白质组学鉴定了与人子宫内膜上皮接受性（“上皮受体”）和滋养外胚层粘附（“ adhesome”）相关的蛋白质。作为验证，关键的“上皮受体组”蛋白（MAGT-1 / CDA / LGMN / KYNU / PC4）定位于可育的正常骑自行车妇女的接受相（分泌中）子宫内膜的上皮，但非接受性受体则基本缺失（增生）相组织。证明了在子宫内膜接受性和植入的连续时间阶段中涉及胚胎-上皮相互作用的因素，并提供了提高生育力的潜在目标，从而增强了自然怀孕或在临床环境中怀孕的可能性。子宫内膜上皮基于这些细胞类型之间的粘附。定量蛋白质组学鉴定了与人子宫内膜上皮接受性（“上皮受体”）和滋养外胚层粘附（“ adhesome”）相关的蛋白质。作为验证，关键的“上皮受体组”蛋白（MAGT-1 / CDA / LGMN / KYNU / PC4）定位于可育的正常骑自行车妇女的接受相（分泌中）子宫内膜的上皮，但非接受性受体则基本缺失（增生）相组织。证明了在子宫内膜容受性和植入的连续时间阶段中涉及胚胎-上皮相互作用的因素，并提供了提高生育力的潜在目标，从而增强了自然怀孕或在临床环境中怀孕的可能性。