title: The effect of prenatal maternal infection on respiratory function in mouse offspring: evidence for enhanced chemosensitivity.
abstract: Systemic maternal inflammation is implicated in preterm birth and bronchopulmonary dysplasia (BPD) and may induce morbidities including reduced pulmonary function, sleep-disordered breathing, and cardiovascular disorders. Here we test the hypothesis that antenatal maternal inflammation per se causes altered alveolar development and increased chemoreflex sensitivity that persists beyond infancy. Pregnant C57BL/6 mice were administered lipopolysaccharide (LPS) (150 μg/kg ip) to induce maternal inflammation or saline (SHAM) at embryonic day 16 (randomized). Pups were weighed daily. On days 7, 28, and 60 (D07, D28, and D60), unrestrained wholebody plethysmography quantified ventilation and chemoreflex responses to hypoxia (10%), hypercapnia (7%), and asphyxia (hypoxic hypercapnia). Lungs were harvested to quantify alveolar number, size, and septal thickness. LPS pups had reduced baseline ventilation per unit bodyweight (∼40%, P < 0.001) vs. SHAM. LPS increased ventilatory responses to hypoxia (D07: 66% vs. 28% increase in ventilation; P < 0.001) hypercapnia (170% vs. 88%; P < 0.001), and asphyxia (249% vs. 154%; P < 0.001); hypersensitive hypoxic responsiveness persisted until D60 (P < 0.001). LPS also increased apnea frequency (P < 0.01). LPS caused thicker alveolar septae (D07, P < 0.001), diminished alveolar number (D28, P < 0.001) vs. SHAM, but effects were minimal by D60. Pups delivered from mothers exposed to antenatal inflammation exhibit deficits in lung structure and hypersensitive responses to respiratory stimuli that persist beyond the newborn period. Antenatal inflammation may contribute to impaired gas exchange and unstable breathing in newborn infants and adversely affect long-term health.
authors.affiliation: Ritchie Centre, MIMR-PHI Institute of Medical Research, Clayton, Victoria, Australia;
authors.forename: Thilini D
authors.initials: TD
authors.lastname: Samarasinghe
authors.affiliation: Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Allergy Immunology and Respiratory Medicine and Central Clinical School, The Alfred and Monash University, Melbourne, Victoria, Australia; and.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Sands
authors.affiliation: Ritchie Centre, MIMR-PHI Institute of Medical Research, Clayton, Victoria, Australia;
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Skuza
authors.affiliation: Kentucky Children's Hospital/UK Healthcare, Department of Pediatrics, University of Kentucky College of Medicine, Lexington, Kentucky.
authors.forename: Mandar S
authors.initials: MS
authors.lastname: Joshi
authors.affiliation: Ritchie Centre, MIMR-PHI Institute of Medical Research, Clayton, Victoria, Australia;
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Nold-Petry
authors.affiliation: Ritchie Centre, MIMR-PHI Institute of Medical Research, Clayton, Victoria, Australia; philip.berger@hudson.org.au.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Berger
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005260:Female; D007249:Inflammation / Q000503:physiopathology*; D008168:Lung / Q000503:physiopathology*; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D011659:Pulmonary Gas Exchange; D012120:Respiration Disorders / Q000503:physiopathology*; D015656:Respiratory Mechanics
keywords: chemosensitivity; prenatal infection; respiratory function