File talk:Human placenta SERPINE2 expression 01.jpg

Spatiotemporal expression of SERPINE2 in the human placenta and its role in extravillous trophoblast migration and invasion

Reprod Biol Endocrinol. 2011 Aug 2;9:106. doi: 10.1186/1477-7827-9-106.

Chern SR1, Li SH, Chiu CL, Chang HH, Chen CP, Tsuen Chen EI. Author information

Abstract BACKGROUND: SERPINE2, one of the potent serpins belonging to the plasminogen activator (PA) system, is involved in the tissue remodeling. We previously demonstrated the expression patterns of Serpine2 in the mouse placenta and uterus, indicating that Serpine2 is a major PA inhibitor in the placenta and uterus during the estrous cycle, pregnancy, and lactation. In this study, we further investigated the expression pattern of SERPINE2 in the human placenta and explored possible functional roles of SERPINE2 in regulating trophoblast activity. METHODS: Placental tissues from various trimesters were collected for real-time reverse-transcription polymerase chain reaction quantification. Immunohistochemical staining was performed in placental tissues to assure localization of SERPINE2. SERPINE2 small interfering (si) RNA was applied to suppress its expression in villous explants and extravillous trophoblast-like 3A cells. Subsequent experiments to evaluate SERPINE2 levels, villous outgrowth, trophoblast invasion, and tube formation were performed. RESULTS: SERPINE2 messenger RNA was detected in the human placenta during pregnancy with the highest levels in the third trimester. The SERPINE2 protein was present in villous syncytiotrophoblasts and trophoblasts of chorionic villi for anti-SERPINE2 immunostaining. Extravillous trophoblasts in the chorionic plate and basal plate confronting the invasive face of anchoring villi were also positive. In most decidual cells, SERPINE2 was observed in the cytoplasm. In addition, fibrinoid deposit was weakly immunoreactive. Introduction of SERPINE2 siRNA into villous explants and trophoblast cells led to significantly reduced villous outgrowth, and trophoblastic migration and invasion. Moreover, capillary-like network formation of 3A cells in Matrigel was greatly attenuated by SERPINE2 siRNA and SERPINE2 antiserum. CONCLUSIONS: These data identify the temporal and spatial SERPINE2 distribution in the human placenta and suggest its possible role in modulating tissue remodeling of extravillous trophoblasts in the placenta during pregnancy.

PMID 21806836

(A) Expression of SERPINE2 mRNA in human placentas in different trimesters. Levels of SERPINE2 mRNA were determined by real-time quantitative PCR in 19 placental tissues collected in three gestational trimesters (T1, T2, and T3; n = 5, 4, and 10, respectively). For each sample, the SERPINE2 expression level was normalized to the expression level of the RPLPO gene in the same sample. Data are presented as the mean ± SEM. * p < 0.05. Immunohistochemical staining showed the distribution of the SERPINE2 protein in the human placenta at gestational week 15. (B) Moderate staining of extravillous trophoblasts (arrow) and decidual cells (arrowhead) in the chorionic plate, and very low staining in the chorionic mesoderm and fibrinoid deposits. (C) Positive immunostaining was extensively detected in decidual cells (dc), cytotrophoblasts, extravillous trophoblasts at the junction zone of the cell column (cc) and anchoring villi (av), and the endothelia of the spiral artery (sa); and weak staining was found in fibrinoids (f) and the villous mesenchyme. (D) The dashed-lined region in 1C was magnified to show intense staining in syncytiotrophoblasts and cytotrophoblasts in floating villi. The invaded extravillous trophoblasts (arrow) and decidual cells (arrowhead) at the basal plate were strongly stained. (E) Positive staining of cytokeratin (CK)-7 was confirmed in syncytiotrophoblasts and cytotrophoblasts in floating villi, and invading trophoblasts (arrow). (F) Upper panels, dashed-lined rectangle regions in D and E were magnified to show strong staining of SERPINE2 (left) and CK-7 (right) in syncytiotrophoblasts (st) and cytotrophoblasts (ct) in floating villi. Lower panels, most of the endothelia of spiral arteries were positively stained with anti-SERPINE2 (left), and anti-CK-7 (right) antibodies. (G) Negative staining of control antiserum. Scale bars represent 200 μm (B, C), and 50 μm (D, E, G).