Age and sex differences in the ventilatory response to hypoxia and hypercapnia in awake neonatal, pre-pubertal and young adult rats

There is evidence for a “sensitive period” in respiratory development in rats around postnatal age (P) 12–13 d. Little is known about sex differences during that time. The purpose of this study was to assess the effect of sex on breathing development, specifically around the “sensitive period”. We used whole-body plethysmography to study breathing in normoxic, hypoxic and hypercapnic gases in non-anesthetized male and female neonatal rats from P10 to P15, juvenile (P30) and young adult (P90) rats. Compared to other neonatal ages, P12–13 male rats had significantly lower ventilation during normoxia, hypoxia, and hypercapnia. Compared to age-matched females, P12–13 male rats had lower ventilation in normoxia and hypoxia and a lower O2 saturation during hypoxia. Circulating estradiol was greater in P12–13 male vs. female rats. Estradiol and ventilatory responses to hypoxia and hypercapnia were negatively correlated in neonatal male, but not female rats. Our results suggest that P10–15 includes a critical developmental period in male but not female rats.

► We examined sex differences in breathing in rats during postnatal days 10–15.
► In hypoxia, P12–13 male rats had lower ventilation and O2 saturation vs. female rats.
► At P12–13, male rats had higher estradiol concentration vs. female rats.
► In male rats, estradiol and hypoxic ventilation had a strong negative correlation.
► P12–13 is a sensitive period of breathing development in male but not in female rats.