title: Gestational stress promotes pathological apneas and sex-specific disruption of respiratory control development in newborn rat.
abstract: Recurrent apneas are important causes of hospitalization and morbidity in newborns. Gestational stress (GS) compromises fetal brain development. Maternal stress and anxiety during gestation are linked to respiratory disorders in newborns; however, the mechanisms remain unknown. Here, we tested the hypothesis that repeated activation of the neuroendocrine response to stress during gestation is sufficient to disrupt the development of respiratory control and augment the occurrence of apneas in newborn rats. Pregnant dams were displaced and exposed to predator odor from days 9 to 19 of gestation. Control dams were undisturbed. Experiments were performed on male and female rats aged between 0 and 4 d old. Apnea frequency decreased with age but was consistently higher in stressed pups than controls. At day 4, GS augmented the proportion of apneas with O(2) desaturations by 12%. During acute hypoxia (12% O(2)), the reflexive increase in breathing augmented with age; however, this response was lower in stressed pups. Instability of respiratory rhythm recorded from medullary preparations decreased with age but was higher in stressed pups than controls. GS reduced medullary serotonin (5-HT) levels in newborn pups by 32%. Bath application of 5-HT and injection of 8-OH-DPAT [(±)-8-hydroxy-2-di-(n-propylamino) tetralin hydrobromide; 5-HT(1A) agonist; in vivo] reduced respiratory instability and apneas; these effects were greater in stressed pups than controls. Sex-specific effects were observed. We conclude that activation of the stress response during gestation is sufficient to disrupt respiratory control development and promote pathological apneas in newborn rats. A deficit in medullary 5-HT contributes to these effects.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Université Laval, Centre de Recherche du CHU de Québec, Hôpital St-François d'Assise, Québec City, Québec, Canada.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Fournier
authors.forename: Shelby
authors.initials: S
authors.lastname: Steele
authors.forename: Cécile
authors.initials: C
authors.lastname: Julien
authors.forename: Sébastien
authors.initials: S
authors.lastname: Fournier
authors.forename: Roumiana
authors.initials: R
authors.lastname: Gulemetova
authors.forename: Céline
authors.initials: C
authors.lastname: Caravagna
authors.forename: Jorge
authors.initials: J
authors.lastname: Soliz
authors.forename: Aida
authors.initials: A
authors.lastname: Bairam
authors.forename: Richard
authors.initials: R
authors.lastname: Kinkead
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001049:Apnea / Q000209:etiology* / Q000503:physiopathology; D003345:Corticosterone / Q000097:blood; D005260:Female; D006935:Hypercapnia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology; D010991:Plethysmography; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D051381:Rats; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology; D012143:Respiratory Physiological Phenomena; D059326:Serotonergic Neurons / Q000502:physiology; D012701:Serotonin / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000503:physiopathology* / Q000523:psychology; D013739:Testosterone / Q000097:blood
chemical_list: D017366:Serotonin Receptor Agonists; D012701:Serotonin; D013739:Testosterone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003345:Corticosterone