Ji Yeon Lee1, Na E Shin2, Quan Na2, Jie Dong2, Anna Chudnovets2, Su Li2, Christopher M Novak2, Michael W McLane2, Jun Lei2, Irina Burd3. 1. Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Obstetrics and Gynecology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Gyeonggi, Republic of Korea. 2. Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 3. Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: iburd@jhmi.edu.
Abstract
PROBLEM: Exposure to systemic maternal inflammation (i.e., maternal sepsis, influenza, human immunodeficiency virus, or pyelonephritis) and intrauterine (IU) inflammation (i.e., chorioamnionitis or preterm labor) have been associated with adverse perinatal sequelae. Whether systemic and localized inflammation leading to adverse outcomes have similar placental mechanisms remain unclear. METHOD OF STUDY: We conducted a study by murine modeling systemic and localized IU inflammation with injections of either intraperitoneal (IP) or IU interleukin-1β (IL-1β) and compared fetoplacental hemodynamic changes, cytokine/chemokine expression, and fetal loss. RESULTS: IU IL-1β exposure reduced offspring survival by 31.1% and IP IL-1β exposure by 34.5% when compared with control pups. Despite this similar outcome in offspring survival, Doppler analysis revealed a stark difference: IU group displayed worsened fetoplacental hemodynamic changes while no differences were found between IP and control groups. While both IU and IP groups had increases in pro-inflammatory cytokines and chemokines, specific gene expression trends differed between the two groups, once again highlighting their mechanistic differences. CONCLUSION: While both IP and IU IL-1β exposure similarly affected pup survival, only IU inflammation resulted in fetoplacental hemodynamic changes. We speculate that exposure to maternal systemic and IU inflammation plays a key role in fetal injury by utilizing different placental inflammatory pathways and mechanisms.
PROBLEM: Exposure to systemic maternal inflammation (i.e., maternal sepsis, influenza, human immunodeficiency virus, or pyelonephritis) and intrauterine (IU) inflammation (i.e., chorioamnionitis or preterm labor) have been associated with adverse perinatal sequelae. Whether systemic and localized inflammation leading to adverse outcomes have similar placental mechanisms remain unclear. METHOD OF STUDY: We conducted a study by murine modeling systemic and localized IU inflammation with injections of either intraperitoneal (IP) or IU interleukin-1β (IL-1β) and compared fetoplacental hemodynamic changes, cytokine/chemokine expression, and fetal loss. RESULTS: IU IL-1β exposure reduced offspring survival by 31.1% and IP IL-1β exposure by 34.5% when compared with control pups. Despite this similar outcome in offspring survival, Doppler analysis revealed a stark difference: IU group displayed worsened fetoplacental hemodynamic changes while no differences were found between IP and control groups. While both IU and IP groups had increases in pro-inflammatory cytokines and chemokines, specific gene expression trends differed between the two groups, once again highlighting their mechanistic differences. CONCLUSION: While both IP and IU IL-1β exposure similarly affected pup survival, only IU inflammation resulted in fetoplacental hemodynamic changes. We speculate that exposure to maternal systemic and IU inflammation plays a key role in fetal injury by utilizing different placental inflammatory pathways and mechanisms.
Authors: Anna Chudnovets; Jun Lei; Quan Na; Jie Dong; Harish Narasimhan; Sabra L Klein; Irina Burd Journal: Am J Reprod Immunol Date: 2020-05-22 Impact factor: 3.886
Authors: Yang Liu; Quan Na; Jin Liu; Anguo Liu; Akosua Oppong; Ji Yeon Lee; Anna Chudnovets; Jun Lei; Rishi Sharma; Sujatha Kannan; Rangaramanujam M Kannan; Irina Burd Journal: Front Bioeng Biotechnol Date: 2022-01-28