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Life-long exposure to hypoxia affects metabolism and respiratory physiology across life stages in high-altitude deer mice (Peromyscus maniculatus)

ABSTRACT Hypoxia exposure can have distinct physiological effects between early developmental and adult life stages, but it is unclear how the effects of hypoxia may progress during continuous exposure throughout life. We examined this issue in deer mice (Peromyscus maniculatus) from a population native to high altitude. Mice were bred in captivity in one of three treatment groups: normoxia (controls), life-long hypoxia (∼12 kPa O2 from conception to adulthood) and parental hypoxia (normoxia from conception to adulthood, but parents previously exposed to hypoxia). Metabolic, thermoregulatory and ventilatory responses to progressive stepwise hypoxia and haematology were then measured at post-natal day (P) 14 and 30 and/or in adulthood. Life-long hypoxia had consistent effects across ages on metabolism, attenuating the declines in O2 consumption rate (V̇O2) and body temperature during progressive hypoxia compared with control mice. However, life-long hypoxia had age-specific effects on breathing, blunting the hypoxia-induced increases in air convection requirement (quotient of total ventilation and V̇O2) at P14 and P30 only, but then shifting breathing pattern towards deeper and/or less frequent breaths at P30 and adulthood. Hypoxia exposure also increased blood–O2 affinity at P14 and P30, in association with an increase in arterial O2 saturation in hypoxia at P30. In contrast, parental hypoxia had no effects on metabolism or breathing, but it increased blood–O2 affinity and decreased red cell haemoglobin content at P14 (but not P30). Therefore, hypoxia exposure has some consistent effects across early life and adulthood, and some other effects that are unique to specific life stages. Summary: Life-long exposure to hypoxia alters hypoxic metabolic depression throughout life with age-specific effects on breathing.