Quantitative analysis of glucose transporter mRNAs in endometrial stromal cells reveals critical role of GLUT1 in uterine receptivity

Recurrent miscarriages affect about 1-2% of couples trying to conceive; however, mechanisms leading to this complication are largely unknown. Most studies focus on the early embryo, but proper development and implantation of the blastocyst are also dependent on optimal endometrial progression into a receptive state. One of the key steps in the uterine preparation for embryo receptivity, known as decidualization, is the differentiation of endometrial stromal cells (ESCs) into decidual cells. During this transition, the ESCs undergoadrastic changeinglucose metabolism. The efficiency of glucose uptake is determined by a family of facilitative glucose transporters (GLUTs), and many have been identified in the stroma. The primary focus of this work was to quantify the absolute amount of GLUT mRNAs in this cell type before and after decidualization. We used primary ESCs isolated from murine and human uteri. We developed and validated cDNA-based calibration curves for each GLUT and used these primers to arrive at absolute mRNA copy numbers. Here, we report all the GLUT mRNAs that are present in the ESCs and their abundance under both conditions, control and decidualized. GLUT1 mRNA is the most abundant and critical transporter in ESCs of both species, because knocking down this GLUT with sort hairpin RNA leads to dramatically reduced decidualization. These findings suggest that GLUT1 mRNA expression is essential for decidualization and we are the first to determine apossiblemechanism toexplainhow maternal conditionsof abnormal glucose utilization may impair implantation at the level of the ESCs.