Anna Chudnovets1, Jun Lei1, Quan Na1, Jie Dong1, Harish Narasimhan2, Sabra L Klein2, Irina Burd1. 1. Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 2. W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Abstract
PROBLEM: Systemic maternal inflammation is associated with adverse neonatal sequelae. We tested the hypothesis that IL-1β is a key inflammatory regulator of adverse pregnancy outcomes. METHOD OF STUDY: Pregnant mice were treated with intraperitoneal injections of IL-1β (0, 0.1, 0.5, or 1 μg) from embryonic day (E)14 to E17. Placenta and fetal brains were harvested and analyzed for morphologic changes and IL-1β signaling markers. RESULTS: As compared with non-treated dams, maternal injections with IL-1β resulted in increased p-NF-κB and caspase-1 in placentas and fetal brains, but not consistently in spleens, suggesting induction of intrinsic IL-1β production. These findings were confirmed by increased levels of IL-1β in the placentas of the IL-1β-treated dams. Systemic treatment of dams with IL-1β suppressed Stat1 signaling. Maternal inflammation caused by IL-1β treatment reduced fetal viability to 80.6% and 58.9%, in dams treated with either 0.5 or 1 μg of IL-1β, respectively. In the placentas, there was an IL-1β dose-dependent distortion of the labyrinth structure, decreased numbers of mononuclear trophoblast giant cells, and reduced proportions of endothelial cells as compared to placentas from control dams. In fetal brains collected at E17, there was an IL-1β dose-dependent reduction in cortical neuronal morphology. CONCLUSION: This work demonstrates that systemic IL-1β injection causes dose-dependent structural and functional changes in the placenta and fetal brain.
PROBLEM: Systemic maternal inflammation is associated with adverse neonatal sequelae. We tested the hypothesis that IL-1β is a key inflammatory regulator of adverse pregnancy outcomes. METHOD OF STUDY: Pregnant mice were treated with intraperitoneal injections of IL-1β (0, 0.1, 0.5, or 1 μg) from embryonic day (E)14 to E17. Placenta and fetal brains were harvested and analyzed for morphologic changes and IL-1β signaling markers. RESULTS: As compared with non-treated dams, maternal injections with IL-1β resulted in increased p-NF-κB and caspase-1 in placentas and fetal brains, but not consistently in spleens, suggesting induction of intrinsic IL-1β production. These findings were confirmed by increased levels of IL-1β in the placentas of the IL-1β-treated dams. Systemic treatment of dams with IL-1β suppressed Stat1 signaling. Maternal inflammation caused by IL-1β treatment reduced fetal viability to 80.6% and 58.9%, in dams treated with either 0.5 or 1 μg of IL-1β, respectively. In the placentas, there was an IL-1β dose-dependent distortion of the labyrinth structure, decreased numbers of mononuclear trophoblast giant cells, and reduced proportions of endothelial cells as compared to placentas from control dams. In fetal brains collected at E17, there was an IL-1β dose-dependent reduction in cortical neuronal morphology. CONCLUSION: This work demonstrates that systemic IL-1β injection causes dose-dependent structural and functional changes in the placenta and fetal brain.
Authors: Michael E Tsimis; Jun Lei; Jason M Rosenzweig; Hattan Arif; Yahya Shabi; Wael Alshehri; Connie C Talbot; K Maravet Baig-Ward; James Segars; Ernest M Graham; Irina Burd Journal: Biol Reprod Date: 2017-08-01 Impact factor: 4.285
Authors: Patrick S Creisher; Jun Lei; Morgan L Sherer; Amanda Dziedzic; Anne E Jedlicka; Harish Narasimhan; Anna Chudnovets; Ariana D Campbell; Anguo Liu; Andrew Pekosz; Irina Burd; Sabra L Klein Journal: Front Virol Date: 2022-02-22
Authors: Morgan L Sherer; Jun Lei; Patrick S Creisher; Minyoung Jang; Ramya Reddy; Kristin Voegtline; Sarah Olson; Kirsten Littlefield; Han-Sol Park; Rebecca L Ursin; Abhinaya Ganesan; Theresa Boyer; Nada Elsayed; Diane M Brown; Samantha N Walch; Annukka A R Antar; Yukari C Manabe; Kimberly Jones-Beatty; William Christopher Golden; Andrew J Satin; Jeanne S Sheffield; Andrew Pekosz; Sabra L Klein; Irina Burd Journal: Am J Obstet Gynecol Date: 2021-03-30 Impact factor: 8.661
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