Prenatal stress challenge impairs fetal lung development and asthma severity sex-specifically in mice. (February 2018)

• Record Type: Journal Article
• Authors: Zazara, Dimitra E.; Perani, Clara V.; Solano, María E.; Arck, Petra C.
• Is Part Of: Journal of reproductive immunology. Volume 125(2018)
• Page Start: 100
• Page End: 105
• Publication Date: 2018-02
• Subjects: Prenatal stress -- Lung development -- Alveolarization -- Regulatory T cells -- Eosinophils; Reproduction -- Immunological aspects -- Periodicals; Immunology -- Periodicals; Allergy and Immunology -- Periodicals; Reproduction -- Periodicals; Reproduction -- Immunologie -- Périodiques; Immunologie -- Périodiques; Immunology; Reproduction -- Immunological aspects; Periodicals; Electronic journals; Electronic journals; 615.766
• DOI: 10.1016/j.jri.2017.07.001
• Languages: English
• ISSNs: 0165-0378

Abstract

Highlights: Prenatal stress challenge sex-specifically disrupts murine fetal lung development in mice. Impaired fetal lung development is linked to an increased severity of airway responsiveness and inflammation in female offspring. Our model allows the identification of maternal markers through which the risk for asthma and possible other diseases is vertically transferred before birth. Abstract: Allergic asthma is an increasing health problem worldwide. Interestingly, prenatal challenges such as stress have been associated with an increased risk for asthma during childhood. The underlying pathogenesis of how prenatal stress increases the risk for asthma still remains unclear. Potential targets could be that the fetal immune ontogeny or fetal lung development are compromised by prenatal challenges. Here, we aimed to identify whether prenatal stress challenge affects fetal lung development in mice. C57BL/6 pregnant mice were challenged with sound stress and fetal lung development was assessed histologically. Whilst prenatal stress challenge did not profoundly affect lung development in male fetuses, it resulted in less extensive terminal sacs, surrounded by thicker mesenchymal tissue in female fetuses. Thus, prenatal stress disrupted fetal lung development sex-specifically. Interestingly, upon prenatal stress challenge, the airway hyperresponsiveness and eosinophilic inflammation- two hallmarks of asthma – were significantly increased in adult female offspring, whilst regulatory CD4+ T cells were reduced. These findings strongly underpin the sex-specific association between s challenged fetal development and a sex-specific altered severity of asthma in adult offspring. Our model now allows to identify maternal markers through which the risk for asthma and possible other diseases is vertically transferred before birth in response to challenges. Such identification then opens avenues for primary disease prevention.