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This Article Full Text Full Text (PDF) All Versions of this Article: 74/1/13    most recent biolreprod.105.044925v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Goldman, S. Articles by Shalev, E. Search for Related Content PubMed PubMed Citation Articles by Goldman, S. Articles by Shalev, E. Agricola Articles by Goldman, S. Articles by Shalev, E.

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

Laboratory for Research in Reproductive Sciences,² Department of Obstetrics and Gynecology, Ha'Emek Medical Center, Afula 18101, Israel Rappaport Faculty of Medicine,³ Technion, Israel Institute of Technology, Haifa 31096, Israel

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.

gene regulation, mechanisms of hormone action, progesterone receptor, steroid hormone receptors, syncytiotrophoblast

¹ Correspondence. FAX: 972 4 649 4032; shaleve{at}tx.technion.ac.il