Language
English
Publication Date
6-3-2026
Journal
Hypertension
DOI
10.1161/HYPERTENSIONAHA.125.26158
PMID
42233183
PMCID
PMC13240661
PubMedCentral® Posted Date
6-6-2026
PubMedCentral® Full Text Version
Author MSS
Abstract
Background: Preeclampsia is a multifactorial, pregnancy-related disorder characterized by new-onset hypertension and proteinuria, with distinct early- and late-onset forms. Although complement dysregulation has been implicated in the pathogenesis of preeclampsia, its causal role remains unclear. In mice, Crry (complement receptor 1-related protein Y) functions as a critical complement regulator at the fetal-maternal interface. Because complete Crry deficiency is embryonically lethal, direct in vivo investigation of complement activation in pregnancy has been challenging.
Methods: We generated a placenta-specific, doxycycline-inducible short hairpin RNA mouse model in which Crry expression can be downregulated in a dose-dependent manner. This system employs Cyp19-driven Cre recombinase and a tetracycline-inducible gene expression system regulatory cassette, enabling precise temporal and spatial control of Crry suppression and restricting complement activation specifically to the placenta.
Results: We found that early gestation placental complement activation impairs maternal cardiac and hepatic adaptation, reduces placental efficiency, and causes fetal growth restriction-features consistent with early-onset preeclampsia. Delayed complement activation produces a phenotype resembling late-onset preeclampsia, characterized by maternal hypertension without placental pathology. In the early-onset-like phenotype, fetal growth restriction is accompanied by placental glycogen storage deficiency and impaired endocrine function. Maternal glucose metabolism remains intact; however, compensatory changes in lipid metabolism occur, although these adaptations are insufficient to prevent fetal growth restriction.
Conclusions: This model demonstrates that the timing of placental complement activation determines whether pregnancy develops early- or late-onset-like features. These findings provide mechanistic insight into how complement dysregulation contributes to the spectrum of preeclampsia pathology and establish a powerful experimental platform for studying disease mechanisms and evaluating therapeutic strategies.
Keywords
Preeclampsia, Complement, Placenta, Pregnancy, Hypertension
Published Open-Access
yes
Recommended Citation
Banadakoppa, Manu T; Chauhan, Madhulatha S; Tacam, Moises J; et al., "Complement Activation in Maternal and Placental Pathology of Preeclampsia" (2026). Faculty, Staff and Students Publications. 7374.
https://digitalcommons.library.tmc.edu/baylor_docs/7374
Graphical Abstract