Department of Physiology I, Eberhard-Karls Universität Tübingen, Tübingen, D-72076, Germany.
Obstetrics, Gynecology, Eberhard-Karls Universität Tübingen, Tübingen, D-72076, Germany.
Sci Rep. 2017 Oct 3;7(1):12612. doi: 10.1038/s41598-017-11674-3.
Embryo implantation requires a hospitable uterine environment. A key metabolic change that occurs during the peri-implantation period, and throughout early pregnancy, is the rise in endometrial glycogen content. Glycogen accumulation requires prior cellular uptake of glucose. Here we show that both human and murine endometrial epithelial cells express the high affinity Na-coupled glucose carrier SGLT1. Ussing chamber experiments revealed electrogenic glucose transport across the endometrium in wild type (Slc5a1 ) but not in SGLT1 deficient (Slc5a1 ) mice. Endometrial glycogen content, litter size and weight of offspring at birth were significantly lower in Slc5a1 mice. In humans, SLC5A1 expression was upregulated upon decidualization of primary endometrial stromal cells. Endometrial SLC5A1 expression during the implantation window was attenuated in patients with recurrent pregnancy loss when compared with control subjects. Our findings reveal a novel mechanism establishing adequate endometrial glycogen stores for pregnancy. Disruption of this histiotrophic pathway leads to adverse pregnancy outcome.
胚胎着床需要一个适宜的子宫环境。在着床期和整个早孕期间，发生的一个关键代谢变化是子宫内膜糖原含量的增加。糖原的积累需要细胞先摄取葡萄糖。在这里，我们表明人源和鼠源的子宫内膜上皮细胞均表达高亲和力 Na 偶联葡萄糖载体 SGLT1。Ussing 室实验表明，在野生型（Slc5a1 ）而非 SGLT1 缺陷型（Slc5a1 ）小鼠中，葡萄糖可通过子宫内膜进行电活性转运。SLC5A1 缺陷型小鼠的子宫内膜糖原含量、产仔数和仔鼠出生体重均显著降低。在人类中，主要子宫内膜基质细胞发生蜕膜化时 SLC5A1 的表达上调。与对照组相比，复发性流产患者着床窗口期的子宫内膜 SLC5A1 表达减弱。我们的研究结果揭示了一种为妊娠建立足够的子宫内膜糖原储备的新机制。这种滋养途径的破坏会导致不良的妊娠结局。
