Meeting Abstract

P2-140   -   Placental gene networks underlying fetal growth restriction at high altitudes Wilsterman, K*; Moore, EC; Good, JM; Cheviron, ZA; University of Montana, Missoula, MT; University of Montana, Missoula, MT; University of Montana, Missoula, MT; University of Montana, Missoula, MT kathrynwilsterman@gmail.com

At high altitudes, lowland mammals universally experience adverse effects on reproductive traits like fetal growth and survival. High altitude-adapted populations of humans and sheep appear to have evolved protections against fetal growth restriction related to altitude, but the mechanisms by which this protection is conferred remain unknown. We recently demonstrated that deer mice (Peromyscus maniculatus) show a similar pattern: lowland deer mice experience fetal growth restriction at simulated altitude, whereas highland-adapted mice preserve fetal growth. Given that placental structure and function are thought to mediate fetal growth outcomes, we hypothesized that adaptation in placental gene networks is involved in both development of and protection from altitude-dependent fetal growth restriction. To understand how adaptation has shaped placental gene networks, we used RNASeq to generate placental transcriptomes from highland-adapted and lowland-derived deer mice gestating at either normobaric normoxia or hypobaric hypoxia in a two-by-two experimental design. Using a weighted gene correlation network analysis (WGCNA) approach, we are (a) identifying groups of co-expressed genes that are associated with fetal growth outcomes, and (b) determining how adaptation has remodeled connectivity of co-expressed genes and hypoxia-dependent plasticity. Together, these analyses identify gene expression patterns and regulatory networks that are associated with altitude-dependent fetal growth restriction in lowlanders, and determine how plasticity in key gene networks protect pregnancies in altitude-adapted populations. Our results provide novel insight into reproductive adaptations to high altitude and advance our understanding of placental adaptations to environmental challenges.