Role of glucose transporter 1 during pregnancy
Pregnancy, an important event in reproduction, involves an intricate relationship between mother and fetus. Implantation and decidualization are characteristic features of early pregnancy. Events during early pregnancy are regulated by steroid hormones, estrogen and progesterone. Our recent studies have indicated that Hif2α is induced by estrogen in the rodent uterus and plays an essential role in embryo implantation. Further studies using gene profiling has shown that Hif2α regulates Glucose transporter1 (GLUT1). GLUT1 is the dominant glucose transporter in the uterus and has been linked to human infertility. Based on these points, we chose to investigate the role of GLUT1 in pregnancy by deleting GLUT1 from the uterus using two transgenic models. The first model consisted of a cross between PRP-Cre mice and mice carrying two copies of the Glut1 floxed gene. The second model was a cross between PR-Cre mice and mice carrying two copies of the Glut1 floxed gene. Our studies revealed that the PRP-Cre model did not effectively delete Glut1 while the PR-Cre model resulted in a deletion of Glut1 in the uterus. The PR-Cre x Glut1 cKO mice were found to be subfertile. Mice lacking Glut1 in the uterus were found to have resorption sites and a disorganized placenta on day 15 of pregnancy. Fetuses and placentas on day 15 of pregnancy were also significantly smaller than control fetuses. By birth, pups from PR-Cre x Glut1 cKO mothers had caught up and were comparable in size to pups from control mothers. When investigating day 18 of pregnancy, pups were found to be nearly comparable to control mice. This indicates that PR-Cre x Glut1 cKO pups could be undergoing rapid growth once the placenta is fully functional. PR-Cre x Glut1 cKO mothers were also found to be hyperglycemic on day 15 of pregnancy, indicating a potential model for gestational diabetes. The combined subfertility and effects seen on day 15 of pregnancy provide evidence that GLUT1 could play an important role in pregnancy.
GLUT1, glucose transporter 1, pregnancy, uterus, subfertility, Prolactin-Related Protein, Progesterone Receptor
University of Illinois - Urbana-Champaign
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University of Illinois at Urbana-Champaign