Effect of progranulin on embryo implantation and placental angiogenesis

Abstract:

Objective：To investigate the effect of progranulin（PGRN） on placental angiogenesis in mice. Methods：Placenta tissue samples were collected from 10 patients with preeclampsia（PE） who underwent caesarean section in The First Affiliated Hospital of Chongqing Medical University from January to April，2017（PE group） and 12 normal controls（NC group）. PCR and Western blot were used to compare the expression of PGRN in the placenta between the PE group and the NC group. Immunofluorescence assay and immunohistochemistry were used to compare angiogenesis in the embryo on day 6.5 of pregnancy and in the placenta on day 17.5 of pregnancy between PGRN-/- mice and normal mice. HE staining was used to compare the diameter and wall thickness of the uterine artery on day 6.5 of pregnancy between groups. Results：The PE group had significantly higher PGRN expression in placenta than the NC group（1.420±0.255 vs. 0.726±0.192，t=4.118，P=0.001）. On day 6.5 of pregnancy，the PGRN-/- mice had a significantly lower number of embryos than the normal mice（5.333±1.154 vs. 9.333±1.527，t=3.618，P=0.022）. The PGRN-/- mice had significantly lower expression of the vascular marker SMA protein than the normal mice in early pregnancy（25 396.600±2 413.606 vs. 17 484.980±1 606.019，t=4.727，P=0.009）. Compared with the normal mice，the PGRN-/- mice had significant reductions in the diameter of the uterine artery（675.844±147.635 vs. 1 022.234±133.902，t=3.010，P=0.039） and muscular thickness of the uterine artery（10.136±1.634 vs. 18.214±2.899，t=4.204，P=0.013）. On day 17.5 of pregnancy，the PGRN-/- mice had significantly lower expression of the vascular markers SMA，COX2，and Tie2 than the normal mice（SMA：626.467±114.744 vs. 5 288.375±871.319，t=9.188，P=0.001；COX2：828.298±29.192 vs. 1169.734±43.490，t=11.290，P=0.000；Tie2：335.766±125.570 vs. 2 415.752±579.038，t=6.080，P=0.003）. Conclusion：PGRN may play a role in the development of pregnancy-related complications by participating in angio－genesis of the embryo and the placenta.