title: Intrauterine growth restriction is a direct consequence of localized maternal uropathogenic Escherichia coli cystitis.
abstract: Despite the continually increasing rates of adverse perinatal outcomes across the globe, the molecular mechanisms that underlie adverse perinatal outcomes are not completely understood. Clinical studies report that 10% of pregnant women will experience a urinary tract infection (UTI) and there is an association of UTIs with adverse perinatal outcomes. We introduced bacterial cystitis into successfully outbred female mice at gestational day 14 to follow pregnancy outcomes and immunological responses to determine the mechanisms that underlie UTI-mediated adverse outcomes. Outbred fetuses from mothers experiencing localized cystitis displayed intrauterine growth restriction (20-80%) as early as 48 hours post-infection and throughout the remainder of normal gestation. Robust infiltration of cellular innate immune effectors was observed in the uteroplacental tissue following introduction of UTI despite absence of viable bacteria. The magnitude of serum proinflammatory cytokines is elevated in the maternal serum during UTI. This study demonstrates that a localized infection can dramatically impact the immunological status as well as the function of non-infected distal organs and tissues. This model can be used as a platform to determine the mechanism(s) by which proinflammatory changes occur between non-contiguous genitourinary organs.
authors.affiliation: Section of Infectious Diseases, Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Bolton
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Horvath
authors.forename: Birong
authors.initials: B
authors.lastname: Li
authors.forename: Hanna
authors.initials: H
authors.lastname: Cortado
authors.forename: David
authors.initials: D
authors.lastname: Newsom
authors.forename: Peter
authors.initials: P
authors.lastname: White
authors.forename: Santiago
authors.initials: S
authors.lastname: Partida-Sanchez
authors.forename: Sheryl S
authors.initials: SS
authors.lastname: Justice
mesh_terms: D000818:Animals; D003556:Cystitis / Q000276:immunology / Q000473:pathology*; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology; D004927:Escherichia coli Infections / Q000209:etiology* / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology / Q000473:pathology; D006801:Humans; D017254:Leukemic Infiltration; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D014158:Transcription, Genetic; D014552:Urinary Tract Infections / Q000209:etiology* / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D056689:Uropathogenic Escherichia coli / Q000302:isolation & purification*
chemical_list: D016207:Cytokines