Paternal deficiency of complement component C1q leads to a preeclampsia-like pregnancy in wild-Type female mice and vascular adaptations postpartum. Am J Physiol Regul Integr Comp Physiol 318: R1047-R1057, 2020. First published May 6, 2020; doi:10.1152/ ajpregu.00353.2019. Preeclampsia is a spontaneously occurring, pregnancy-specific syndrome that is clinically diagnosed by new onset hypertension and proteinuria. Epidemiological evidence describes an association between a history of preeclampsia and increased risk for cardiovascular disease in later life; however, the mechanism(s) driving this relationship are unclear. Our study aims to leverage a novel preeclampsia-like mouse model, the C1q/ model, to help elucidate the acute and persistent vascular changes during and following a preeclampsia-like pregnancy. Female C57BL/6J mice were mated to C1q/ male mice to model a preeclampsia-like pregnancy ("PElike"), and the maternal cardiovascular phenotype (blood pressure, renal function, systemic glycocalyx, and ex vivo vascular function) was assessed in late pregnancy and postpartum at 6 and 10 mo of age. Uncomplicated, normotensive pregnancies (female C57BL/6J bred to male C57BL/6J mice) served as age-matched controls. In pregnancy, PE-like dams exhibited increased systolic and diastolic pressure during mid-and late gestation, renal dysfunction, fetal growth restriction, and reduced placental efficiency. Ex vivo wire myography studies of mesenteric arteries revealed severe pregnancy-specific endothelial-dependent and-independent vascular dysfunction. At 3 and 7 mo postpartum (6 and 10 mo old, respectively), hypertension resolved in PE-like dams, whereas mild vascular dysfunction persisted at 3 mo postpartum. In conclusion, the female C57BL/6J-by-male C57BL/6J C1q/ model recapitulates many aspects of the human preeclampsia syndrome in a low-risk, wild-Type female mouse. The pregnancy-specific phenotype results in systemic maternal endothelial-dependent and-independent vascular dysfunction that persists postpartum.
|Journal||American Journal of Physiology - Regulatory Integrative and Comparative Physiology|
|Publication status||Published - 28 May 2020|
- vascular function