In utero development of fetal breathing movements in C57BL6 mice

Fetuses of many species, including humans, breathe during development. This fetal breathing aids in lung development, strengthens respiratory muscles, and is posited to fine-tune the neural circuitry that drives breathing. Previous studies suggested that fetal breathing could begin as early as the fifteenth day of gestation in the mouse, but fetal breathing movements (FBMs) had not been observed in mice in utero. We aimed to determine if and when FBMs commence in mice and if they change over time. We examined unanesthetised pregnant C57BL6 mice with ultrasound beginning on the seventh day of gestation. We first reliably observed episodic FBMs in mice on embryonic day 16. FBMs were sporadic, clustered, or rhythmic, and their frequency increased with age. Ultrasound examination of FBMs in mice has great potential utility in the study of transgenic mouse models to help us understand the prenatal characteristics of breathing related human developmental disorders, including Congenital Central Hypoventilation Syndrome (CCHS) and apnea of prematurity.