MBL Interferes with Endovascular Trophoblast Invasion in Pre-Eclampsia

Abstract

The spiral arteries undergo physiologic changes during pregnancy, and the failure of this process may lead to a spectrum of pregnancy disorders, including pre-eclampsia. Our recent data indicate that decidual endothelial cells (DECs), covering the inner side of the spiral arteries, acquire the ability to synthesize C1q, which acts as a link between endovascular trophoblast and DECs favouring the process of vascular remodelling. In this study, we have shown that sera obtained from pre-eclamptic patients strongly inhibit the interaction between extravillous trophoblast (EVT) and DECs, preventing endovascular invasion of trophoblast cells. We further demonstrated that mannose-binding lectin (MBL), one of the factor increased in pre-eclamptic patient sera, strongly inhibits the interaction of EVT with C1q interfering with the process of EVT adhesion to and migration through DECs. These data suggest that the increased level of MBL in pre-eclampsia may contribute to the failure of the endovascular invasion of trophoblast cells.

The Complement System and Preeclampsia

“…MBL is also increased in women with preeclampsia compared to normal pregnancy [58]. MBL, an initiating factor for the lectin pathway of complement activation, is reported to interfere with the bridging ability of C1q [59]. Collectively these data suggest that the presence of C1q is important in the development of a normal placenta, irrespective of its role in initiation of the classical complement pathway.…”

The complement system and adverse pregnancy outcomes

“…In vitro studies suggest that C1q is likely a bridge allowing adherence of decidual endothelial cells and the endovascular trophoblast. MBL is known to inhibit this interaction (Agostinis et al, 2012). Moreover, MBL is increased in normal pregnancy compared to non-pregnant women (van de Geijn et al, 2007) suggesting it may play a role in limiting endovascular trophoblast invasion of spiral arteries.…”

Differential levels of surfactant protein A, surfactant protein D, and progesterone to estradiol ratio in maternal serum before and after the onset of severe early‐onset preeclampsia

“…In total, 35 It is to be noted that the hospitals involved in the present study are tertiary referral hospitals and many participants discontinue their subsequent visits and prefer to visit the local hospitals. A total of 922 healthy pregnant women in the age group of 21-35 years were recruited in the prospective study at their first antenatal care (ANC) visit (≤20 weeks of gestation).…”

“…To the best of our knowledge, reasons for the elevated levels of E2 at 10-20 weeks of gestation in the women with severe EOPE are not known. Role of elevated levels of MBL in the immunopathogenesis of PE has been documented previously in Caucasian population [33][34][35]. Also, increased serum E2 levels in the first trimester in human IVF studies have been associated with impaired placentation and pregnancy complications, including preeclampsia (PE) and low birthweight 52,53.…”

“…16,[25][26][27][28] In addition to their role in host defense and parturition in pregnancy, differential expression of collectins has been associated with various inflammation-driven pregnancy complications. [33][34][35] These reports enticed us to investigate whether collectin expression is dysregulated in PE. 29 Decreased maternal serum MBL levels are associated with recurrent spontaneous abortions.…”