Recurrent implantation failure (RIF) is defined as the failed pregnancy after good embryo transfer over 3 cycles during in vitro fertilization (IVF).The human endometrium plays a vital role in providing the site for embryo implantation, with several factors implicated in unsatisfactory endometrial receptivity in RIF. Our present results revealed that women with pregnancy loss or infertility have a higher serum epinephrine level, indicating a potential correlation between psychological stress and pregnancy failure. RNA-sequencing of the tissues collected at the endometrial receptive phase in normal and RIF women showed that stress hormones could affect the functional status of endometrial receptivity. Subsequent analysis revealed that the epinephrine signaling acts as an important regulator of endometrial receptivity through the PI3K-AKT and FOXO1 signaling pathways. We also found that patients with RIF show attenuated expression of the alpha-2C-adrenergic receptor (ADRA2C) and that its down regulation induced by high level epinephrine could inhibit the decidualization. Early pregnant mice treated with stress showed high serum epinephrine levels, defective uterine adrenergic receptor expression, and low pregnancy rates. Altogether, our findings indicate that mental stress during early pregnancy can alter the functional status of endometrial receptivity.

复发性植入失败 (RIF) 定义为在体外受精 (IVF) 过程中经过 3 个周期的良好胚胎移植后失败的妊娠。人类子宫内膜在提供胚胎植入部位方面起着至关重要的作用，其中有几个因素与子宫内膜容受性不满意有关在 RIF 中。我们目前的结果显示，流产或不孕的女性血清肾上腺素水平较高，表明心理压力与妊娠失败之间存在潜在相关性。对正常和 RIF 女性子宫内膜容受期收集的组织进行 RNA 测序表明，应激激素可能影响子宫内膜容受性的功能状态。随后的分析表明，肾上腺素信号通过 PI3K-AKT 和 FOXO1 信号通路作为子宫内膜容受性的重要调节剂。我们还发现，RIF 患者的 α-2C-肾上腺素能受体 (ADRA2C) 表达减弱，高水平肾上腺素诱导其下调可抑制蜕膜化。接受压力治疗的早孕小鼠表现出高血清肾上腺素水平、子宫肾上腺素能受体表达缺陷和低妊娠率。总之，我们的研究结果表明，妊娠早期的精神压力可以改变子宫内膜容受性的功能状态。我们还发现，RIF 患者的 α-2C-肾上腺素能受体 (ADRA2C) 表达减弱，高水平肾上腺素诱导其下调可抑制蜕膜化。接受压力治疗的早孕小鼠表现出高血清肾上腺素水平、子宫肾上腺素能受体表达缺陷和低妊娠率。总之，我们的研究结果表明，妊娠早期的精神压力可以改变子宫内膜容受性的功能状态。我们还发现，RIF 患者的 α-2C-肾上腺素能受体 (ADRA2C) 表达减弱，高水平肾上腺素诱导其下调可抑制蜕膜化。接受压力治疗的早孕小鼠表现出高血清肾上腺素水平、子宫肾上腺素能受体表达缺陷和低妊娠率。总之，我们的研究结果表明，妊娠早期的精神压力可以改变子宫内膜容受性的功能状态。