Endogenous Erythropoietin is a Sex Specific Respiratory Stimulant in Newborn and Adult Mice.

Abstract

We hypothesized that endogenous brain Erythropoietin (Epo) is a sex‐specific respiratory stimulant in newborn (10 days old) and adult (3 months) mice. Mice received an intracisternal injection of soluble Epo receptor (sEpoR – antagonist of EpoR) or control. 24 hours after injection, we used whole body plethysmography to record respiratory frequency (fR), tidal volume (VT), and minute ventilation (VE=fRxVT), O2 consumption (VO2) and CO2 production (VCO2) under normoxia and exposure to moderate (12‐10% O2) and severe hypoxia (6% O2) – 10 minutes each. In normoxia, sEpoR decreased VE in adult and newborn mice, but this effect was sex‐specific as sEpoR decreased fR in females and Vt in males. The ventilatory response to moderate hypoxia (assessed as VE/VO2 or VE/VCO2) is decreased in newborn male and female mice after injection of sEpoR, but in adult mice this effect was present only in males. During severe hypoxia, newborn male and female mice treated with sEpoR show signs of respiratory depression and asphyxia (gasping). We conclude that endogenous Epo is a potent endogenous respiratory stimulant in newborn and adult mice, that sex‐specific effects are present under normoxic conditions in newborn and adult mice, and that under hypoxic exposure, sex‐specific effects are present only in adult mice. Funded by CIHR (mop: 130258).