engleski

Type 1 Diabetes Is Associated with Impaired Placental MMP Expression in Early Pregnancy

Results: In the first trimester of pregnancy placental trophoblast cells invade the maternal uterine wall in order to anchor the placenta and to establish adequate utero-placental blood flow by remodelling of the uterine arteries. Therefore, trophoblasts are well equipped with matrix degrading enzymes i.e. matrix metalloproteinases (MMPs). Maternal T1D is associated with a higher risk for early pregnancy loss, pre-eclampsia and fetal growth restriction. As underlying reason we hypothesise impaired trophoblast invasion. Because placental changes in early gestation are difficult to determine, indirect evidence is needed to demonstrate changes in trophoblast invasion. The aim of the present study was to identify changes in MMP expression in first trimester placentas from healthy vs. T1D pregnancies. Additionally, the effect of low oxygen on MMP expression was determined in a first trimester trophoblast cell line (ACH-3P). First trimester placentas from normal (n=15) vs. T1D (n=12) pregnancies between gestational week 6 and 10 were obtained after pregnancy interruption for psycho-social reasons and immediately frozen in liquid nitrogen. Total RNA was isolated and mRNA expression of all 23 human MMPs was measured using sqRT-PCR and analyzed according to the gestational weeks. Expression signals were normalized to the trophoblast marker cytokeratin 7. ACH-3P cells were cultured under various oxygen concentrations (2.5, 5, 12, 21) for seven days and expression of MMPs was measured similarly. In the first trimester, the placenta expresses 14 MMPs. T1D was associated with a reduced expression of 11 MMPs in weeks 8-10. Hypoxia reduced expression of various MMPs in ACH-3P cells. This is the first study to demonstrate altered placental MMP expression during early human pregnancy as a result of maternal T1D. T1D is associated with a decrease of MMP expression which may hence impair the process of trophoblast invasion. Lower uterine oxygen concentrations as a result of diabetes may be involved in the impaired MMP expression. These results may explain the higher incidence of spontaneous abortions in T1D women and their higher risk for pre-eclampsia and IUGR in late pregnancy.

Type 1 diabetes mellitus; MMP; pregnancy

nije evidentirano