Contrasting effects of estradiol and progesterone on respiratory pattern and hypoxic ventilatory response in newborn male rats

Abstract

We tested the hypothesis that postnatal exposure to progesterone or estradiol exerts distinct effects on respiratory control, apnea frequency, and on hypoxic ventilatory response (HVR). To this aim, we assessed breathing pattern using whole body plethysmography in normoxia and during a sustained hypoxic exposure (10% O(2)-30min) in 10-day-old male rats raised by dams implanted with osmotic minipumps delivering either estradiol (E(2), 7.0microgday(-1)), estradiol+progesterone (E(2)+P, 7.0+70microgday(-1)) or vehicle (propylene glycol) at a regular flow rate throughout postnatal days 1-14. Compared to vehicle, E(2) and E(2)+P pups had a reduced ventilation, metabolic rate and rectal temperature. HVR was specifically increased in E(2)+P pups compared to controls and E(2) pups. On the contrary, both E(2) and E(2)+P pups did not reduced metabolism as much as controls during hypoxic exposure, and the decrease in rectal temperature was abolished. Surprisingly, E(2)+P pups showed a dramatic elevation of sigh frequency, while progesterone (in E(2)+P compared to E(2) and Veh pups) reduced apnea frequency. These findings are relevant to better understand the role of placental steroids on respiratory and metabolic control during early development in rats, and could ultimately contribute to a better understanding of specific respiratory control disorders in preterm neonates, which are chronically deprived from placental steroids exposure.