{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T06:18:29Z","timestamp":1792736309415,"version":"4.5.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T00:00:00Z","timestamp":1673481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science National Center of Neurology and Psychiatry","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Gestational intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea that occurs frequently during pregnancy, and effects caused by this environmental change during pregnancy may be transmitted to the offspring. In this study, we aimed to clarify the effects of IH in pregnant rats on the skeletal muscle of adolescent offspring rats. Mother rats underwent IH from gestation day 7\u201321, and their 5-weeks-old male offspring were analyzed. All male offspring rats were born and raised under normoxia conditions. Although no general growth retardation was observed, we found that exposure to gestational IH reduces endurance running capacity of adolescent offspring rats. Both a respiratory muscle (diaphragm; DIA) and a limb muscle (tibialis anterior; TA) showed no histological abnormalities, including fiber size and fiber type distribution. To identify the possible mechanism underlying the reduced running capacity, regulatory factors associated with energy metabolism were analyzed in different parts of skeletal muscles. Compared with rats born under conditions of gestational normoxia, gestational IH offspring rats showed significantly lower expression of genes associated with glucose and lipid metabolism, and lower protein levels of phosphorylated AMPK and AKT. Furthermore, gene expression of adiponectin receptors one and two was significantly decreased in the DIA and TA muscles. In addition, the DIA muscle from adolescent rats had significantly decreased capillary density as a result of gestational IH. However, these changes were not observed in a sucking muscle (geniohyoid) and a masticating muscle (masseter) of these rats. These results suggest that respiratory and limb muscles are vulnerable to gestational IH, which induces altered energy metabolism with decreased aerobic motor function. These changes were partially owing to the decreased expression of adiponectin receptors and decreased capillary density in adolescent offspring rats.<\/jats:p>","DOI":"10.3389\/fphys.2023.1067683","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T07:01:51Z","timestamp":1673506911000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia"],"prefix":"10.3389","volume":"14","author":[{"given":"Wirongrong","family":"Wongkitikamjorn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Wada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Hosomichi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirichom","family":"Satrawaha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixin","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken-ichi","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko K.","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1164\/ajrccm.153.2.8564147","article-title":"Standards and indications for cardiopulmonary sleep studies in children. American Thoracic Society","volume":"153","year":"1996","journal-title":"Am. Thorac. Soc. Am J Respir Crit Care Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"5349","DOI":"10.1113\/JP277936","article-title":"Gestational intermittent hypoxia induces endothelial dysfunction, reduces perivascular adiponectin and causes epigenetic changes in adult male offspring","volume":"597","author":"Badran","year":"2019","journal-title":"J. Physiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"16","DOI":"10.13172\/2052-0069-2-2-571","article-title":"Development of aerobic metabolism in utero: Requirement for mitochondrial function during embryonic and fetal periods","volume":"2","author":"Baker","year":"2013","journal-title":"OA Biotechnol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1046\/j.1469-0705.1997.09030162.x","article-title":"Demonstration of fetal coronary blood flow by Doppler ultrasound in relation to arterial and venous flow velocity waveforms and perinatal outcome--the 'heart-sparing effect","volume":"9","author":"Baschat","year":"1997","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"583","DOI":"10.2337\/db06-1432","article-title":"Opposing effects of adiponectin receptors 1 and 2 on energy metabolism","volume":"56","author":"Bjursell","year":"2007","journal-title":"Diabetes"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e35273","DOI":"10.1371\/journal.pone.0035273","article-title":"Rapid determination of myosin heavy chain expression in rat, mouse, and human skeletal muscle using multicolor immunofluorescence analysis","volume":"7","author":"Bloemberg","year":"2012","journal-title":"PloS one"},{"key":"B7","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1096\/fj.10-158188","article-title":"Prenatal hypoxia independent of undernutrition promotes molecular markers of insulin resistance in adult offspring","volume":"25","author":"Camm","year":"2011","journal-title":"FASEB J."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1002\/cphy.c140073","article-title":"Placental gas exchange and the oxygen supply to the fetus","volume":"5","author":"Carter","year":"2015","journal-title":"Compr. Physiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s13395-016-0088-4","article-title":"The SH3 and cysteine-rich domain 3 (Stac3) gene is important to growth, fiber composition, and calcium release from the sarcoplasmic reticulum in postnatal skeletal muscle","volume":"6","author":"Cong","year":"2016","journal-title":"Skelet. Muscle"},{"key":"B10","doi-asserted-by":"publisher","first-page":"165","DOI":"10.5534\/wjmh.210021","article-title":"Consequences of anabolic-androgenic steroid abuse in males; sexual and reproductive perspective","volume":"40","author":"Corona","year":"2022","journal-title":"World J. Mens. Health"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2144","DOI":"10.1210\/en.2014-1131","article-title":"Sexual dimorphism in offspring glucose-sensitive hypothalamic gene expression and physiological responses to maternal high-fat diet feeding","volume":"155","author":"Dearden","year":"2014","journal-title":"Endocrinology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1378\/chest.14-0500","article-title":"Intermittent hypoxemia and OSA: Implications for comorbidities","volume":"147","author":"Dewan","year":"2015","journal-title":"Chest"},{"key":"B13","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1007\/978-0-387-73693-8_80","article-title":"Oxidative stress impairs upper airway muscle endurance in an animal model of sleep-disordered breathing","volume-title":"Integration in respiratory control: From genes to systems","author":"Dunleavy","year":"2008"},{"key":"B14","doi-asserted-by":"publisher","first-page":"3923","DOI":"10.3390\/ijms21113923","article-title":"Age dependent modification of the metabolic profile of the tibialis anterior muscle fibers in C57bl\/6J mice","volume":"21","author":"Giacomello","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e31017","DOI":"10.1371\/journal.pone.0031017","article-title":"Developmental programming of cardiovascular dysfunction by prenatal hypoxia and oxidative stress","volume":"7","author":"Giussani","year":"2012","journal-title":"PLoS One"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1164\/rccm.200208-963OC","article-title":"Respiratory effects of gestational intermittent hypoxia in the developing rat","volume":"167","author":"Gozal","year":"2003","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"3416","DOI":"10.1210\/EN.2015-1394","article-title":"Developmental origins of health and disease: Integrating environmental influences","volume":"156","author":"Heindel","year":"2015","journal-title":"Endocrinology"},{"key":"B19","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1152\/japplphysiol.91382.2008","article-title":"Higher intramuscular triacylglycerol in women does not impair insulin sensitivity and proximal insulin signaling","volume":"107","author":"H\u00f8eg","year":"2009","journal-title":"J. Appl. Physiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"676270","DOI":"10.3389\/fphys.2021.676270","article-title":"Selective \u03b22-adrenoceptor blockade rescues mandibular growth retardation in adolescent rats exposed to chronic intermittent hypoxia","volume":"12","author":"Hong","year":"2021","journal-title":"Front. Physiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"401323","DOI":"10.1155\/2010\/401323","article-title":"Causes and mechanisms of intrauterine hypoxia and its impact on the fetal cardiovascular system: A review","volume":"2010","author":"Hutter","year":"2010","journal-title":"Int. J. Pediatr."},{"key":"B22","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1183\/20734735.009215","article-title":"Sleep disordered breathing in pregnancy","volume":"11","author":"Izci Balserak","year":"2015","journal-title":"Breathe Sheff. Engl."},{"key":"B23","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1183\/09031936.06.00148204","article-title":"Sleep-disordered breathing and upper airway size in pregnancy and post-partum","volume":"27","author":"Izci","year":"2006","journal-title":"Eur. Respir. J."},{"key":"B24","doi-asserted-by":"publisher","first-page":"3230","DOI":"10.2337\/db14-0202","article-title":"Sleep fragmentation during late gestation induces metabolic perturbations and epigenetic changes in adiponectin gene expression in male adult offspring mice","volume":"63","author":"Khalyfa","year":"2014","journal-title":"Diabetes"},{"key":"B25","doi-asserted-by":"publisher","first-page":"2551","DOI":"10.1113\/JP273570","article-title":"Late gestational intermittent hypoxia induces metabolic and epigenetic changes in male adult offspring mice","volume":"595","author":"Khalyfa","year":"2017","journal-title":"J. Physiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1016\/s0143-4004(97)90000-x","article-title":"Oxygen and placental villous development: Origins of fetal hypoxia","volume":"18","author":"Kingdom","year":"1997","journal-title":"Placenta"},{"key":"B27","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.acthis.2019.04.001","article-title":"Effect of hypoxia on the muscle fiber switching signal pathways CnA\/NFATc1 and myostatin in mouse myocytes","volume":"121","author":"Lixin","year":"2019","journal-title":"Acta Histochem."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1776","DOI":"10.1172\/JCI29044","article-title":"AMP-activated protein kinase signaling in metabolic regulation","volume":"116","author":"Long","year":"2006","journal-title":"J. Clin. Invest."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1097\/AOG.0b013e31826eb9d8","article-title":"Perinatal outcomes associated with obstructive sleep apnea in obese pregnant women","volume":"120","author":"Louis","year":"2012","journal-title":"Obstet. Gynecol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1016\/j.bbadis.2013.02.014","article-title":"Intermittent-hypoxia induced autophagy attenuates contractile dysfunction and myocardial injury in rat heart","volume":"1832","author":"Maeda","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"B31","doi-asserted-by":"publisher","first-page":"276","DOI":"10.3389\/fphys.2016.00276","article-title":"Effects of gestational and postnatal exposure to chronic intermittent hypoxia on diaphragm muscle contractile function in the rat","volume":"7","author":"McDonald","year":"2016","journal-title":"Front. Physiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"E1107","DOI":"10.1152\/ajpendo.1997.273.6.E1107","article-title":"AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle","volume":"273","author":"Merrill","year":"1997","journal-title":"Am. J. Physiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"307","DOI":"10.4103\/2348-8093.149770","article-title":"A novel system including an N2 gas generator and an air compressor for inducing intermittent or chronic hypoxia","volume":"1","author":"Nagai","year":"2014","journal-title":"Int. J. Clin. Exp. Physiology"},{"key":"B33","doi-asserted-by":"publisher","first-page":"R1181","DOI":"10.1152\/ajpregu.00208.2014","article-title":"Therapeutic potential of intermittent hypoxia: A matter of dose","volume":"307","author":"Navarrete-Opazo","year":"2014","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1016\/s0140-6736(87)90292-3","article-title":"Maternal oxygen therapy for intrauterine growth retardation","volume":"329","author":"Nicolaides","year":"1987","journal-title":"Lancet"},{"key":"B35","doi-asserted-by":"publisher","first-page":"e15031","DOI":"10.14814\/phy2.15031","article-title":"Sex differences in skeletal muscle revealed through fiber type, capillarity, and transcriptomics profiling in mice","volume":"9","author":"O'Reilly","year":"2021","journal-title":"Physiol. Rep."},{"key":"B36","doi-asserted-by":"publisher","first-page":"16200","DOI":"10.1074\/jbc.M114.548115","article-title":"Divergent roles for adiponectin receptor 1 (AdipoR1) and AdipoR2 in mediating revascularization and metabolic dysfunction in vivo","volume":"289","author":"Parker-Duffen","year":"2014","journal-title":"J. Biol. Chem."},{"key":"B37","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1111\/j.1469-7793.2000.00525.x","article-title":"Prenatal hypoxia impairs the postnatal development of neural and functional chemoafferent pathway in rat","volume":"524","author":"Peyronnet","year":"2000","journal-title":"J. Physiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"312","DOI":"10.3389\/fcell.2019.00312","article-title":"Adult muscle stem cells: Exploring the links between systemic and cellular metabolism","volume":"7","author":"Purohit","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"507","DOI":"10.2337\/db10-1239","article-title":"Hypoxia-induced intrauterine growth restriction increases the susceptibility of rats to high-fat diet-induced metabolic syndrome","volume":"60","author":"Rueda-Clausen","year":"2011","journal-title":"Diabetes"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e98119","DOI":"10.1371\/journal.pone.0098119","article-title":"Fibre-specific responses to endurance and low volume high intensity interval training: Striking similarities in acute and chronic adaptation","volume":"9","author":"Scribbans","year":"2014","journal-title":"PLoS One"},{"key":"B41","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1369\/0022155413490947","article-title":"Diaphragm muscle remodeling in a rat model of chronic intermittent hypoxia","volume":"61","author":"Shortt","year":"2013","journal-title":"J. Histochem Cytochem"},{"key":"B42","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1113\/expphysiol.2013.076828","article-title":"Reactive oxygen species mediated diaphragm fatigue in a rat model of chronic intermittent hypoxia","volume":"99","author":"Shortt","year":"2014","journal-title":"Exp. Physiol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1071\/RD16265","article-title":"Sex-specific differences and developmental programming for diseases in later life","volume":"29","author":"Sundrani","year":"2017","journal-title":"Reprod. Fertil. Dev."},{"key":"B44","doi-asserted-by":"publisher","first-page":"2885","DOI":"10.3390\/ijms23052885","article-title":"Prenatal hypoxia affects foetal cardiovascular regulatory mechanisms in a sex- and circadian-dependent manner: A review","volume":"23","author":"Sutovska","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/hr.2016.21","article-title":"Prenatal hypoxia in rats increased blood pressure and sympathetic drive of the adult offspring","volume":"39","author":"Svitok","year":"2016","journal-title":"Hypertens. Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"e0221512","DOI":"10.1371\/journal.pone.0221512","article-title":"Deficiency of emerin contributes differently to the pathogenesis of skeletal and cardiac muscles in LmnaH222P\/H222P mutant mice","volume":"14","author":"Wada","year":"2019","journal-title":"PLoS One"},{"key":"B47","doi-asserted-by":"publisher","first-page":"755554","DOI":"10.3389\/fnins.2021.755554","article-title":"Effects of prenatal hypoxia on nervous system development and related diseases","volume":"15","author":"Wang","year":"2021","journal-title":"Front. Neurosci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s13395-016-0117-3","article-title":"Voluntary resistance wheel exercise from mid-life prevents sarcopenia and increases markers of mitochondrial function and autophagy in muscles of old male and female C57BL\/6J mice","volume":"6","author":"White","year":"2016","journal-title":"Skelet. Muscle"},{"key":"B49","doi-asserted-by":"publisher","first-page":"e25088","DOI":"10.7759\/cureus.25088","article-title":"Gestational intermittent hypoxia induces mitochondrial impairment in the geniohyoid muscle of offspring rats","volume":"14","author":"Wongkitikamjorn","year":"2022","journal-title":"Cureus"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1038\/nm788","article-title":"Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase","volume":"8","author":"Yamauchi","year":"2002","journal-title":"Nat. Med."},{"key":"B51","doi-asserted-by":"publisher","first-page":"561","DOI":"10.3389\/fendo.2020.00561","article-title":"High-intensity interval training restores glycolipid metabolism and mitochondrial function in skeletal muscle of mice with type 2 diabetes","volume":"11","author":"Zheng","year":"2020","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"B52","doi-asserted-by":"publisher","first-page":"15983","DOI":"10.1073\/pnas.252625599","article-title":"AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation","volume":"99","author":"Zong","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U. S. A."}],"updated-by":[{"DOI":"10.3389\/fphys.2024.1518152","type":"corrigendum","label":"Corrigendum","source":"publisher","updated":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T00:00:00Z","timestamp":1733184000000}}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2023.1067683\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T13:12:06Z","timestamp":1733231526000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2023.1067683\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,12]]},"references-count":52,"alternative-id":["10.3389\/fphys.2023.1067683"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2023.1067683","relation":{"corrigendum":[{"id-type":"doi","id":"10.3389\/fphys.2024.1518152","asserted-by":"object"}]},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,12]]},"article-number":"1067683"}}