Hypertension (Dallas, Tex. : 1979) · 2026
Complement Activation in Maternal and Placental Pathology of Preeclampsia.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Banadakoppa Manu T, Chauhan Madhu S, Tacam Moises J, Nevins Allyson W, Ruano Antonio H, Ruano Simone H, Fuson Jon A, Yallampalli Chandra
Аннотация
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.
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.