Gestating at altitude: How do maternal physiology and evolutionary adaptation influence fetal growth?

Lowland mammals, including humans, experience an increased risk for fetal growth restriction (FGR) at high altitudes. FGR is associated with a range of adverse lifetime risks, including lower infant survival. Maternal physiology, such as cardiopulmonary function and nutrient provisioning, has been hypothesized to play an important role in driving altitude-dependent FGR, but strong associations between specific aspects of maternal physiology and FGR at altitude have been difficult to establish. One approach has been to study populations adapted to altitude; highland populations of humans, sheep, and deer mice (Peromyscus maniculatus) mitigate altitude-induced reductions in fetal growth and may thus offer insight into the relevant underlying physiology. We assessed the relationship between measures of maternal physiology and fetal growth outcomes using deer mice derived from highland-adapted and lowland populations that gestated under normoxia or hypobaric hypoxia. At late pregnancy, we measured fetal mass along with an array of physiological measures from dams (e.g., body and organ masses, and blood hematocrit and glucose). Using linear modeling, we assessed the relationships between maternal physiology and fetal growth phenotypes. To investigate the possibility that fetal growth is a function of many incremental changes in physiology, we compressed dimensionality of the maternal physiology data using PCA and then used the reduced dimensions in a linear modeling framework. The results from our study will add to our broader understanding of how maternal physiology shapes fetal growth, and they will help expand our understanding of the physiological systems that contribute to altitude adaptation across mammals