{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:20:59Z","timestamp":1788916859817,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"abstract":"Abstract<\/jats:title>Gestational hypoxia reduces fetal growth and birth weight across mammals, including humans. Evolutionary adaptation to high\u2010elevation hypoxia mitigates these negative effects, and identifying these protective mechanisms may offer insight into how environmental factors interact with gestational physiology to influence health outcomes. We know that gestational hypoxia modifies development of the placenta, which mediates maternal\u2013fetal exchange, but little is known about how high\u2010altitude adaptation interacts with this developmental plasticity to influence placental exchange capacity. We tested the hypothesis that hypoxia\u2010dependent remodelling of the placental exchange surface is protective for fetal growth and thus will be exaggerated in highland\u2010adapted individuals by using a model rodent system, the North American deer mouse. We acclimated lowland\u2010 and highland\u2010ancestry deer mice to normoxia or hypoxia (12.3% O2<\/jats:sub>) during gestation and found that lowland\u2010ancestry deer mice expand their placenta and maternal blood spaces in the placenta in response to environmental hypoxia. Highland\u2010ancestry deer mice produce even larger placentas and maternal blood spaces, suggesting that these hypoxia\u2010driven responses may benefit fetal growth by increasing total exchange capacity. Notably, we also found that the fetal blood spaces in highland\u2010ancestry placentas have increased perimeter (a proxy for surface area) per unit area occupied by blood. Similar changes to fetal vasculature have been observed in high\u2010elevation\u2010adapted human populations, which is suggestive of convergent adaptation. Our results demonstrate that the hypoxia\u2010sensitive development of placental vasculature is remodelled by adaptation to environmental hypoxia and that some of these processes may be points for convergent adaptation across species despite distinct placental architectures.\nimage<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>Key points<\/jats:title>\nEvolutionary adaptation to high elevations provides protection against hypoxia\u2010dependent fetal growth restriction.<\/jats:p><\/jats:list-item>\nThe placenta is a key determinant of fetal growth because it defines the total surface area available for nutrient and gas exchange between the gestational parent and offspring.<\/jats:p><\/jats:list-item>\nWe tested the hypothesis that evolutionary adaptation to high elevations protects fetal growth by increasing placental surface area for exchange using acclimation experiments in a model rodent system, the North American deer mouse.<\/jats:p><\/jats:list-item>\nAs we predicted, high\u2010elevation ancestry increased the size of maternal blood spaces in the placenta, especially under gestational hypoxia; however, highland ancestry was also associated with narrower fetal blood spaces, which could increase exchange efficiency.<\/jats:p><\/jats:list-item>\nThe patterns observed in deer mice resemble developmental plasticity observed in placentas from humans with high\u2010elevation ancestry, pointing to potential for convergent adaptation across species with distinct placental architectures.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp289376","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T20:19:46Z","timestamp":1758140386000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["High\u2010elevation adaptation and gestational hypoxia jointly shape vascular development in a rodent placenta"],"prefix":"10.1113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7262-9754","authenticated-orcid":false,"given":"Kathryn","family":"Wilsterman","sequence":"first","affiliation":[{"name":"Department of Biology Colorado State University Fort Collins CO USA"},{"name":"Cellular and Molecular Biology Graduate Program Colorado State University Fort Collins Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary A.","family":"Cheviron","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences University of Montana Missoula MT USA"},{"name":"Wildlife Biology Program University of Montana Missoula MT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Good","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences University of Montana Missoula MT USA"},{"name":"Wildlife Biology Program University of Montana Missoula MT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Gurnoe\u2010Brantley","sequence":"additional","affiliation":[{"name":"Department of Biology Colorado State University Fort Collins CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kylie E.","family":"Jewett","sequence":"additional","affiliation":[{"name":"Department of Biology Colorado State University Fort Collins CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Kiel","sequence":"additional","affiliation":[{"name":"Department of Biology Colorado State University Fort Collins CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1393-0592","authenticated-orcid":false,"given":"Ashley M.","family":"Larson","sequence":"additional","affiliation":[{"name":"Department of Biology Colorado State University Fort Collins CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"issue":"1","key":"e_1_2_5_2_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting linear mixed\u2010effects models using lme4","volume":"67","author":"Bates D.","year":"2015","journal-title":"Journal of Statistical Software"},{"key":"e_1_2_5_3_1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.placenta.2023.08.068","article-title":"A review of feto\u2010placental vasculature flow modelling","volume":"142","author":"Chappell J.","year":"2023","journal-title":"Placenta"},{"issue":"22","key":"e_1_2_5_4_1","doi-asserted-by":"crossref","first-page":"8635","DOI":"10.1073\/pnas.1120523109","article-title":"Regulatory changes contribute to the adaptive enhancement of thermogenic capacity in high\u2010altitude deer mice","volume":"109","author":"Cheviron Z. 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