Preeclampsia is a spontaneously occurring pregnancy complication diagnosed by new onset hypertension and end-organ dysfunction with or without proteinuria. This pregnancy-specific syndrome contributes to maternal morbidity and mortality and can have detrimental effects on fetal outcome. Preeclampsia is also linked to increased risk of maternal cardiovascular disease throughout life. Despite intense investigation of this disorder, few treatment options are available. The aim of this study was to investigate the potential therapeutic effects of maternal L-citrulline supplementation on pregnancy-specific vascular dysfunction in the ♀ C57BL/6J x ♂ C57BL/6J C1q-/- preeclampsia-like mouse model. L-citrulline is a non-essential amino acid that is converted to L-arginine to promote smooth muscle and blood vessel relaxation and improve nitric oxide (NO) mediated vascular function. To model a preeclampsia-like pregnancy, female C57BL/6J mice were mated to C1q-/- male mice, and a subset of dams were supplemented with L-citrulline throughout pregnancy. Blood pressure, systemic vascular glycocalyx, and ex-vivo vascular function were investigated in late pregnancy, and postpartum at 6 and 10 months of age. Main findings show that L-citrulline reduced blood pressure, increased vascular glycocalyx volume and rescued ex-vivo vascular function at gestation day 17.5 in this preeclampsia-like model. The vascular benefit of L-citrulline also extended postpartum, with improved vascular function and glycocalyx measures at 6 and 10 months of age. L-citrulline mediated vascular improvements appear, in part, attributable to NO pathway signaling. Taken together, L-citrulline supplementation during pregnancy appears to have beneficial effects on maternal vascular health which may have translational implications for improved maternal cardiovascular health.

Preeclampsia, a pregnancy specific syndrome characterized by new onset hypertension and proteinuria, is a leading cause of maternal and neonatal morbidity and mortality. While no animal model perfectly mimics the human syndrome, breeding C1q-/- (male) to C57 (female) mice results in a preeclampsia-like pregnancy including pregnancy-specific hypertension, vascular dysfunction and altering placental phenotype. As the placental genotype is primarily paternally driven, lack of paternal C1q is likely driving this preeclampsia-like phenotype. However, more work is needed to investigate whether a lack of maternal C1q also contributes to this preeclampsia-like phenotype. The aim of this study was to investigate the pregnancy phenotype of genetic control (C1q-/- female bred to C57 male) mice. Blood pressure was monitored during pregnancy and vascular function assessed during late pregnancy (gestation day 17.5) in genetic control females. These data were compared to similar data obtained from control (C57 male bred to C57 female) and preeclampsia-like (C1q-/- male bred to C57 female) pregnant mice. Genetic control blood pressure and vascular function data were similar to that of the control pregnancy group, indicating no significant effect of maternal C1q deficiency on the “preeclampsia-like” pregnancy phenotype. As understanding preeclampsia and its effect on women’s health is critical, the work presented is important to confirm the C1q-/- x C57 mouse model as a useful model for studying this syndrome further.

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