Complement Component 1q Deficiency Impairs Maternal Hemodynamic Adaptations to Pregnancy, Decidual Vascular...

Pregnancy complications such as preeclampsia and fetal growth restriction are caused by compromised placentation associated with impaired maternal cardiovascular and immune adaptation to pregnancy, but the pathophysiological pathways underlying these impairments are not fully defined. C1q (complement component 1q) plays a central role in immune cell recruitment, functional regulation, and immune tolerance. In this study, we investigated the impact of maternal C1q deficiency on maternal uterine and systemic cardiovascular parameters in pregnancy.

C1q null mutant (C1qa^-/-) and C57BL/6 wild-type control female mice were mated with BALB/c males. Cardiovascular adaptations were investigated by echocardiography and wire myography, as well as uterine artery ultrasound and decidual spiral artery assessment.

C1qa^-/- dams exhibited increased fetal loss (↑3.6-fold; P=0.011) and late gestation fetal growth restriction, notably among male fetuses (P=0.002). Mesenteric arteries from C1qa^-/- dams displayed heightened vasoconstriction ex vivo (area under the curve ↑34%; P=0.018). In midpregnancy, C1qa^-/- dams exhibited uterine artery dysfunction (resistance index ↑23%; P=0.014), defective decidual spiral artery remodeling (vessel wall thickness: ↑16%; P=0.010), and reduced decidual perivascular macrophages surrounding spiral arteries (↓28%; P=0.050) compared with control dams.

These findings indicate that maternal C1q deficiency disrupts key cardiovascular adaptations to pregnancy, likely contributing to poor fetal outcomes via impaired maternal hemodynamics and constrained placental function. This study identifies maternal C1q as a critical regulator of pregnancy-induced vascular adaptation and supports mounting evidence for C1q relevance in pregnancy complications involving placental insufficiency.