The study investigated the effect of normal and supraphysiological (resulting from gonadotropin-dependent ovarian stimulation) levels of estradiol (E2) and progesterone (P4) on mouse uterine aquaporin gene/protein (Aqp/AQP) expression on Day 1 (D1) and D4 of pregnancy. The study also examined the effect of ovarian stimulation on uterine luminal closure and uterine receptivity on D4 of pregnancy and embryo implantation on D5 and D7 of pregnancy. These analyses revealed that the expression of Aqp3, Aqp4, Aqp5 and Aqp8 is induced by E2 while the expression of Aqp1 and Aqp11 is induced by P4. Additionally, P4 inhibits E2 induction of Aqp3 and Aqp4 expression while E2 inhibits Aqp1 and Aqp11 expression. Aqp9, however, is constitutively expressed. Ovarian stimulation disrupts Aqp3, Aqp5 and Aqp8 expression on D4 and AQP1, AQP3 and AQP5 spatial expression on both D1 and D4, strikingly so in the myometrium. Interestingly, while ovarian stimulation has no overt effect on luminal closure and uterine receptivity, it reduces implantation events, likely through a disruption in myometrial activity and embryo development. The wider implication of this study is that ovarian stimulation, which results in supraphysiological levels of E2 and P4 and changes (depending on the degree of stimulation) in the E2:P4 ratio, triggers abnormal expression of uterine AQP during pregnancy, and this is associated with implantation failure. These findings lead us to recognize that abnormal expression would also occur under any pathological state (such as endometriosis) that is associated with changes in the normal E2:P4 ratio. Thus, infertility among these patients might in part be linked to abnormal uterine AQP expression.

中文翻译：

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子宫水通道蛋白的表达受到雌二醇和黄体酮的动态调节，卵巢刺激会破坏胚胎植入而不影响管腔闭合。


该研究调查了正常和超生理（由促性腺激素依赖性卵巢刺激引起）雌二醇 (E2) 和黄体酮 (P4) 水平对第 1 天 (D1) 和 D4 小鼠子宫水通道蛋白基因/蛋白 (Aqp/AQP) 表达的影响怀孕的。该研究还考察了卵巢刺激对妊娠第 4 天子宫腔闭合和子宫容受性以及妊娠第 5 和第 7 天胚胎植入的影响。这些分析表明，E2 诱导 Aqp3、Aqp4、Aqp5 和 Aqp8 的表达，而 P4 诱导 Aqp1 和 Aqp11 的表达。此外，P4 抑制 E2 诱导 Aqp3 和 Aqp4 表达，而 E2 抑制 Aqp1 和 Aqp11 表达。然而，Aqp9 是组成型表达的。卵巢刺激会破坏 D4 上的 Aqp3、Aqp5 和 Aqp8 表达，以及 D1 和 D4 上的 AQP1、AQP3 和 AQP5 空间表达，在子宫肌层中尤其如此。有趣的是，虽然卵巢刺激对管腔闭合和子宫容受性没有明显影响，但它可能通过破坏子宫肌层活动和胚胎发育来减少着床事件。这项研究更广泛的意义是，卵巢刺激会导致 E2 和 P4 的超生理水平以及 E2:P4 比例的变化（取决于刺激程度），从而引发妊娠期间子宫 AQP 的异常表达，这与并伴有植入失败。这些发现使我们认识到，在任何与正常 E2:P4 比率变化相关的病理状态（例如子宫内膜异位症）下也会发生异常表达。因此，这些患者的不孕可能部分与子宫 AQP 表达异常有关。