Purpose: We have previously demonstrated that C1q, the first component of the classic complement cascade, is involved in the placentation process acting as a molecular bridge between endovascular trophoblast and decidual endothelial cell1 and promoting trophoblast interstitial invasion2. We observed also a deficient trophoblast invasion in implantation sites of C1q-/- mice if compared to WT animals; so we hypothesized that C1q could had a role in the onset of pre-eclampsia, a multisystem syndrome characterized by a defect of placentation. Methods: Placental mRNA derived from 7 pre-eclamptic (PE) patients and 6 healthy matched controls were analyzed by qPCR for C1q expression. PE sections were stained for C1q and cytokeratin 7 to identify trophoblast. The expression of MMP12 by on freshly isolated trophoblast cells adhering to C1q, FN or poly-L-Lysine was detected by qPCR and immunofluorescence. Results: C1q expression was found to be significantly lower in PE placentae compared to healthy women. Histological evidences on PE decidual sections showed that trophoblast cells surrounding non-remodelled spiral artery do not express C1q in comparison to non pathological placentae. In vitro studies on trophoblast cells demonstrated that the expression of MMP-12, a marker of vascular remodelling3, is upregulated in response to C1q interaction. Discussion: The defective staining of C1q by PE perivascular trophoblast seems to be directly related to absence of vascular remodelling. The upregulation of MMP-12 expression by trophoblast cells in response to C1q indicated a functional role of C1q in trophoblast vascular remodelling. Conclusions: Collectively, these data support the pivotal role played by C1q in placental development. The importance of this component at the placental level is evidenced by its involvement in pregnancy disorders such as pre-eclampsia, characterized by poor trophoblast invasion.
Pre-eclampsia is associated with defective production of C1q by invasive trophoblast
Chiara Agostinis;Fleur Bossi;Oriano Radillo;Giuseppe Ricci;Tamara Stampalija;Leila Lo Bello;Romana Vidergar;Leonardo Amadio;Francesco Tedesco;Roberta Bulla
2017-01-01
Abstract
Purpose: We have previously demonstrated that C1q, the first component of the classic complement cascade, is involved in the placentation process acting as a molecular bridge between endovascular trophoblast and decidual endothelial cell1 and promoting trophoblast interstitial invasion2. We observed also a deficient trophoblast invasion in implantation sites of C1q-/- mice if compared to WT animals; so we hypothesized that C1q could had a role in the onset of pre-eclampsia, a multisystem syndrome characterized by a defect of placentation. Methods: Placental mRNA derived from 7 pre-eclamptic (PE) patients and 6 healthy matched controls were analyzed by qPCR for C1q expression. PE sections were stained for C1q and cytokeratin 7 to identify trophoblast. The expression of MMP12 by on freshly isolated trophoblast cells adhering to C1q, FN or poly-L-Lysine was detected by qPCR and immunofluorescence. Results: C1q expression was found to be significantly lower in PE placentae compared to healthy women. Histological evidences on PE decidual sections showed that trophoblast cells surrounding non-remodelled spiral artery do not express C1q in comparison to non pathological placentae. In vitro studies on trophoblast cells demonstrated that the expression of MMP-12, a marker of vascular remodelling3, is upregulated in response to C1q interaction. Discussion: The defective staining of C1q by PE perivascular trophoblast seems to be directly related to absence of vascular remodelling. The upregulation of MMP-12 expression by trophoblast cells in response to C1q indicated a functional role of C1q in trophoblast vascular remodelling. Conclusions: Collectively, these data support the pivotal role played by C1q in placental development. The importance of this component at the placental level is evidenced by its involvement in pregnancy disorders such as pre-eclampsia, characterized by poor trophoblast invasion.File | Dimensione | Formato | |
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