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Prenatal stress challenge impairs fetal lung development and asthma severity sex-specifically in mice
Dimitra E Zazara1, Clara V Perani1, María E Solano1
1Department of Obstetrics and Prenatal Medicine, Laboratory for Experimental Feto-Maternal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Insights
Prenatal stress impacts fetal lung development differently in male and female mice. This sex-specific disruption in development leads to increased asthma severity in adult female offspring.
Area of Science:
- Reproductive biology
- Developmental biology
- Immunology
Background:
- Allergic asthma is a growing global health concern.
- Prenatal stress is linked to increased childhood asthma risk, but the mechanisms are unclear.
- Potential mechanisms involve compromised fetal immune development or lung development.
Purpose of the Study:
- To investigate the sex-specific effects of prenatal stress on fetal lung development in mice.
- To explore the link between prenatal stress, fetal development, and asthma severity in offspring.
Main Methods:
- Pregnant C57BL/6 mice were exposed to sound stress.
- Fetal lung development was assessed using histological analysis.
- Airway hyperresponsiveness, inflammation, and T cell populations were evaluated in adult offspring.
Main Results:
- Prenatal stress caused sex-specific disruptions in fetal lung development.
- Female fetuses showed reduced terminal sacs and thicker mesenchymal tissue.
- Adult female offspring exhibited increased airway hyperresponsiveness and eosinophilic inflammation, with reduced regulatory CD4+ T cells.
Conclusions:
- Prenatal stress disrupts fetal lung development in a sex-specific manner.
- This disruption is associated with increased asthma severity in adult female offspring.
- The findings highlight the potential for vertically transferred risk factors for asthma and other diseases 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.
