The effect of prenatal maternal infection on respiratory function in mouse offspring: evidence for enhanced chemosensitivity
| Autor: | Thilini Samarasinghe, Claudia A. Nold-Petry, Scott A. Sands, Elizabeth M. Skuza, Mandar S. Joshi, Philip J. Berger |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Inflammation
Physiology business.industry Offspring Pulmonary Gas Exchange medicine.disease Respiration Disorders Maternal inflammation Pulmonary function testing Maternal infection Mice Inbred C57BL Bronchopulmonary dysplasia Animals Newborn Pregnancy Physiology (medical) Prenatal Exposure Delayed Effects Immunology Breathing Respiratory Mechanics Medicine Animals Respiratory function Female business Lung |
| Zdroj: | Journal of applied physiology (Bethesda, Md. : 1985). 119(3) |
| ISSN: | 1522-1601 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|