Distinct Mechanisms Underlie Developmental Plasticity and Adult Acclimation of Thermogenic Capacity in High-Altitude Deer Mice

Abstract

Developmental plasticity can elicit phenotypic adjustments that help organisms cope with environmental change, but the relationship between developmental plasticity and plasticity in adult life (e.g., acclimation) remains unresolved. We sought to examine developmental plasticity and adult acclimation in response to hypoxia of aerobic capacity (V̇O2max) for thermogenesis in deer mice (Peromyscus maniculatus) native to high altitude. Deer mice were bred in captivity and exposed to normoxia or one of four hypoxia treatments (12 kPa O2) across life stages: adult hypoxia (6–8 weeks), post-natal hypoxia (birth to adulthood), life-long hypoxia (before conception to adulthood), and parental hypoxia (mice conceived and raised in normoxia, but parents previously exposed to hypoxia). Hypoxia during perinatal development increased V̇O2max by a much greater magnitude than adult hypoxia. The amplified effect of developmental hypoxia resulted from physiological plasticity that did not occur with adult hypoxia – namely, increases in lung ventilation and volume. Evolved characteristics of deer mice enabled developmental plasticity, because white-footed mice (P. leucopus; a congener restricted to low altitudes) could not raise pups in hypoxia. Parental hypoxia had no persistent effects on V̇O2max. Therefore, developmental plasticity can have much stronger phenotypic effects and can manifest from distinct physiological mechanisms from adult acclimation.

Changes in CYP3A4 Enzyme Expression and Biochemical Markers Under Acute Hypoxia Affect the Pharmacokinetics of Sildenafil

“…First, the blood gas index of each group of rats was measured, because its changes can prove the hypoxia of the body and affect the pharmacokinetic characteristics of the drug ( Wang et al, 2016 ). Previous studies have shown that hypoxia increases hemoglobin levels in rats and cells ( Grek et al, 2011 ; Ivy et al, 2021 ). This study also found that acute hypoxia reduced SaO 2 , PaCO 2 , PaO 2 , and SBC, and increased Lac and Hb.…”

Gene regulatory changes underlie developmental plasticity in respiration and aerobic performance in highland deer mice

“…In a recent study of highland deer mice from the Rocky Mountains, Ivy et al (2021) found that exposure to hypoxia during early development improved both ventilation and whole-animal aerobic performance (cold-induced VO 2 max) during hypoxia in adulthood, and the magnitude of these improvements depended on the stage of developmental exposure. Normoxic controls were compared to mice exposed to hypoxia starting at three different life stages and extending into adulthood: life-long hypoxia (before conception to adulthood); post-natal hypoxia (birth to adulthood); and adult hypoxia (6-8 weeks only during adulthood).…”

“…The enhanced aerobic performance under hypoxia is associated with increased survivorship in free-ranging mice at high elevation (Hayes & O’Connor, 1999) and is associated with plastic and genetically based modifications across the oxygen transport cascade (Ivy & Scott, 2015; Schweizer et al, 2021, 2019; Storz & Cheviron, 2020; Storz et al, 2019; Storz & Scott, 2019). Research into the ontogeny of these differences has only just begun, but some components of the unique physiology of highlanders is clearly manifest within the first few weeks of life (Ivy et al, 2020; Ivy et al, 2021; Robertson et al, 2019; Velotta et al, 2020). The plastic responses to hypoxia also differ between highland and lowland mice.…”

“…The plastic responses to hypoxia also differ between highland and lowland mice. For example, hypoxia exposure during adulthood improves ventilation in lowlanders, but it has no effect on the ventilatory phenotypes of highlanders (Ivy & Scott, 2017; Ivy et al, 2021; Ivy & Scott, 2017).…”

“…In this study, we examine gene expression changes in the diaphragm that underlie plastic responses to hypoxia exposure at different life stages. We focus on the diaphragm because of its central role in mammalian ventilation, and because our previous studies of highland deer mice suggest that developmental plasticity in diaphragm form and function may mediate changes in several respiratory traits that contribute to aerobic metabolism and performance under hypoxia (Catherine M Ivy et al, 2021). We address three interrelated questions: 1) What are the underlying gene regulatory changes that contribute to plastic responses to hypoxia in early development and adulthood?…”