Difference in Progesterone-Receptor Isoforms Ratio Between Early and Late First-Trimester Human Trophoblast Is Associated with Differential Cell Invasion and Matrix Metalloproteinase 2 Expression

Abstract

The expression profile of the progesterone-receptor isoforms and progesterone regulation of matrix metalloproteinase 2 (MMP2) were investigated in early and late first-trimester trophoblast cells. Human trophoblast cells were obtained from legal abortions (6-12 wk of gestation). Purity of 95-98% was verified using immunohistochemistry with specific antibodies. Evaluation of cell count was performed with XTT Reagent kit, and invasion was tested using Matrigel invasion assay. Zymography was used to detect proteolytic activity, and Western blot immunoassay was used to study protein concentration. Gene expression of PGRB, PGR, and MMP2 was studied using reverse transcription-polymerase chain reaction with the housekeeping gene GAPDH used for normalization. Promoter activity was determined using luciferase reporter assay. Differential progesterone-receptor profile was documented with the dominance of PGRB in early trophoblast and the dominance of PGRA in late trophoblast. This differential profile is compatible with the inverse effect of progesterone on the two cell populations, decreasing invasion and gelatinase expression in the early first-trimester trophoblast and increasing invasion and gelatinase expression in the late first-trimester trophoblast. A decrease in MMP2 promoter activity in early trophoblast cells exposed to progesterone suggests that MMP2 expression is regulated by progesterone at the transcriptional level as well. Early trophoblast cells transfected with expressing vector for PGR encoding PGRA revealed less MMP2 activity and reversal of its response to progesterone similar to the effect observed in late trophoblast cells.

The DSCs-Expressed CD82 Controls the Invasiveness of Trophoblast Cells via Integrinbeta1/MAPK/MAPK3/1 Signaling Pathway in Human First-Trimester Pregnancy1

“…Human CG can stimulate trophoblast migration through IGF2 [38] and MMP9 [39]. Progesterone may decrease invasion and gelatinase expression in trophoblast cells of the first trimester, but increase the invasion and MMP2 expression in trophoblast cells of the late pregnancy [40]. We have demonstrated that hCG attenuates CD82 expression in DSCs, but estrogen or progesterone has no effect on the CD82 expression.…”

The Effects of Decidual Injury on the Invasion Potential of Trophoblastic Cells

“…Our group and others have described this quality in previous reports. [13][14][15] This may explain why more than half of trophoblast cells in model 1 migrated through the porous membrane of the upper well into the lower well without a target tissue. In contrast, decidual explants in this study were retrieved from term pregnancy.…”

Impact of silencing MMP9 gene on the biological behaviors of trophoblasts

“…MMPs can regulate the dynamic equilibrium between the decomposition and reconstruction of ECM by breaking down the components of ECM, in order to remove some special signals, reveal some hidden signals, even help to release or activate some bio-active substances found in the matrix, thereby contributing to the structural and functional changes of cells, tissues or organs [8] . In the process of embryo implantation, trophoblasts release large amounts of MMP1, MMP2 and MMP9 [9][10][11] . In MMPs family, MMP9 belongs to collagenase subgroup and is predominantly responsible for the cleavage of basement membrane of cells [12] , thereby promoting the infiltration of trophoblasts into the uterine endometrial stroma and spiral arteries of the placental bed and helping to establish good feto-placental circulation.…”