{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:57:01Z","timestamp":1792648621005,"version":"4.5.0"},"reference-count":46,"publisher":"The Company of Biologists","issue":"4","license":[{"start":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T00:00:00Z","timestamp":1649808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Khalifa University of Science and Technology","award":["CIRA 2019-023"],"award-info":[{"award-number":["CIRA 2019-023"]}]},{"name":"Khalifa University of Science and Technology","award":["8474000174"],"award-info":[{"award-number":["8474000174"]}]},{"name":"RIKEN Healthcare and Medical Data Platform Project; Grand-in-Aid for Scientific Research; the Creative Interdisciplinary Research Project of Frontier Research Institute for Interdisciplinary Science","award":["20K09590"],"award-info":[{"award-number":["20K09590"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>This study examines the role of autonomic control of maternal and fetal heart rate variability (MHRV and FHRV) and their heartbeats phase coupling prevalence (CPheartbeat) in mice. The subjects are divided into three groups: control with saline, cholinergic blockade with atropine, and \u03b2-adrenergic blockade with propranolol. Electrocardiogram signals of 27 anesthetized pregnant mice and 48 fetuses were measured for 20\u2005min (drugs were administered after 10\u2005min). For the coupling analysis, different maternal heartbeats were considered for one fetal beat. Results show that saline infusion did not produce any significant changes in MHRV and FHRV, as well as CPheartbeat. Atropine increased maternal HR (MHR) and decreased MHRV significantly without any considerable effect on fetal HR (FHR) and FHRV. Propranolol infusion did not produce any significant changes in MHR and MHRV, but significantly decreased FHR and increased FHRV. Moreover, atropine had led to a decrease in CPheartbeat when considering two and three maternal beats, and an increase for four beats; while propranolol resulted in a decrease for two heartbeats, but an increase for four and five beats. The proposed approach is useful for assessing the impact of maternal autonomic modulation activity on fetal distress and obstetric complications prevalent in pregnant mothers.<\/jats:p>","DOI":"10.1242\/bio.058999","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T15:05:42Z","timestamp":1645455942000},"source":"Crossref","is-referenced-by-count":9,"title":["Investigating the effect of cholinergic and adrenergic blocking agents on maternal-fetal heart rates and their interactions in mice fetuses"],"prefix":"10.1242","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0636-1646","authenticated-orcid":false,"given":"Ahsan H.","family":"Khandoker","sequence":"first","affiliation":[{"name":"Health Engineering Innovation Center (HEIC), Department of Biomedical Engineering, Khalifa University, Abu Dhabi 127788, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3747-2469","authenticated-orcid":false,"given":"Maisam","family":"Wahbah","sequence":"additional","affiliation":[{"name":"Health Engineering Innovation Center (HEIC), Department of Biomedical Engineering, Khalifa University, Abu Dhabi 127788, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chihiro","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Maternal and Fetal Therapeutics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9508-2218","authenticated-orcid":false,"given":"Yoshiyuki","family":"Kasahara","sequence":"additional","affiliation":[{"name":"Department of Maternal and Fetal Therapeutics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, 980-8575, Japan"},{"name":"Department of Maternal and Child Health Care Medical Science, Tohoku University Graduate School of Medicine, Sendai, Miyagi, 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5978-2655","authenticated-orcid":false,"given":"Kiyoe","family":"Funamoto","sequence":"additional","affiliation":[{"name":"Health Engineering Innovation Center (HEIC), Department of Biomedical Engineering, Khalifa University, Abu Dhabi 127788, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6958-5527","authenticated-orcid":false,"given":"Kyuichi","family":"Niizeki","sequence":"additional","affiliation":[{"name":"Department of Biosystems Engineering, Graduate School of Science and Engineering, Yamagata University, Yonezawa, Yamagata, 992-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Maternal and Fetal Therapeutics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2022,4,13]]},"reference":[{"key":"2022041307412115700_BIO058999C1","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/s12576-012-0248-1","article-title":"The mechanism of increased postnatal heart rate and sinoatrial node pacemaker activity in mice","volume":"63","author":"Adachi","year":"2013","journal-title":"J. Physiol. Sci."},{"key":"2022041307412115700_BIO058999C2","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/S1566-0702(00)00271-X","article-title":"Effects of ketamine and propofol on autonomic cardiovascular function in chronically instrumented rats","volume":"87","author":"Akine","year":"2001","journal-title":"Auton. Neurosci."},{"key":"2022041307412115700_BIO058999C3","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/0306-3623(78)90044-7","article-title":"Effects of ketamine on the isolated perfused rat heart","volume":"9","author":"Aronson","year":"1978","journal-title":"Gen. Pharmacol. Vasc. Syst."},{"key":"2022041307412115700_BIO058999C4","doi-asserted-by":"publisher","first-page":"R1378","DOI":"10.1152\/ajpregu.1994.267.5.R1378","article-title":"Sympathetic activity and blood pressure are tightly coupled at 0.4 Hz in conscious rats","volume":"267","author":"Brown","year":"1994","journal-title":"Am. J. Physiol. Integr. Comp. Physiol."},{"key":"2022041307412115700_BIO058999C5","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1177\/0192623317728134","article-title":"Histology atlas of the developing prenatal and postnatal mouse central nervous system, with emphasis on prenatal days E7.5 to E18.5","volume":"45","author":"Chen","year":"2017","journal-title":"Toxicol. Pathol."},{"key":"2022041307412115700_BIO058999C6","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.expneurol.2013.05.015","article-title":"Lack of type VI adenylyl cyclase (AC6) leads to abnormal sympathetic tone in neonatal mice","volume":"248","author":"Chien","year":"2013","journal-title":"Exp. Neurol."},{"key":"2022041307412115700_BIO058999C7","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1111\/j.1472-8206.2007.00502.x","article-title":"Sympathetic control of short-term heart rate variability and its pharmacological modulation","volume":"21","author":"Elghozi","year":"2007","journal-title":"Fundam. Clin. Pharmacol."},{"key":"2022041307412115700_BIO058999C8","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1007\/978-3-642-04898-2_420","article-title":"Nonparametric statistical inference","volume-title":"International Encyclopedia of Statistical Science","author":"Gibbons","year":"2011"},{"key":"2022041307412115700_BIO058999C9","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1242\/bio.015750","article-title":"Prickle1 mutation causes planar cell polarity and directional cell migration defects associated with cardiac outflow tract anomalies and other structural birth defects","volume":"5","author":"Gibbs","year":"2016","journal-title":"Biol. Open"},{"key":"2022041307412115700_BIO058999C10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1469-7580.2007.00833.x","article-title":"Cells migrating from the neural crest contribute to the innervation of the venous pole of the heart","volume":"212","author":"Hildreth","year":"2007","journal-title":"J. Anat."},{"key":"2022041307412115700_BIO058999C11","doi-asserted-by":"publisher","first-page":"13641","DOI":"10.1073\/pnas.0906987106","article-title":"Maternal-fetal heartbeat phase synchronization","volume":"106","author":"Ivanov","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2022041307412115700_BIO058999C12","doi-asserted-by":"publisher","first-page":"81","DOI":"10.3109\/00016348409157129","article-title":"The acute effects of a non-selective \u03b2-adrenergic blocking agent in hypertensive pregnant rats","volume":"63","author":"Karlsson","year":"1984","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"2022041307412115700_BIO058999C13","volume-title":"The Atlas of Mouse Development","author":"Kaufman","year":"1992","edition":"1st edn"},{"key":"2022041307412115700_BIO058999C14","doi-asserted-by":"publisher","first-page":"177","DOI":"10.15388\/Informatica.2011.321","article-title":"The burg algorithm with extrapolation for improving the frequency estimation","volume":"22","author":"Kazlauskas","year":"2011","journal-title":"Informatica"},{"key":"2022041307412115700_BIO058999C15","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1161\/01.RES.79.2.247","article-title":"In vivo assessment of embryonic cardiovascular dimensions and function in day-10.5 to \u221214.5 mouse embryos","volume":"79","author":"Keller","year":"1996","journal-title":"Circ. Res."},{"key":"2022041307412115700_BIO058999C16","first-page":"2954","article-title":"Assessment of autonomic neurodevelopment in the mouse fetuses by using fetal electrocardiography","author":"Khandoker","year":"2016"},{"key":"2022041307412115700_BIO058999C17","first-page":"1","article-title":"Effect of chronic hypoxia on autonomic nervous system of fetal mice","author":"Khandoker","year":"2017"},{"key":"2022041307412115700_BIO058999C18","first-page":"5257","article-title":"Regulation of maternal-fetal heart rates and coupling in mice fetuses","author":"Khandoker","year":"2018"},{"key":"2022041307412115700_BIO058999C19","first-page":"1","article-title":"Effect of anesthesia on fetal-maternal heart rate variability and coupling in pregnant mice and fetuses","author":"Khandoker","year":"2020"},{"key":"2022041307412115700_BIO058999C20","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1007\/BF01457415","article-title":"Muscarinic receptors in the prenatal mouse embryo. Comparison of M35-immunohistochemistry with [3H]quinuclidinyl benzylate autoradiography","volume":"103","author":"Lammerding-Koppel","year":"1995","journal-title":"Histochem. Cell Biol."},{"key":"2022041307412115700_BIO058999C21","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/S0165-1838(00)00075-8","article-title":"Sympathetic activity in the rat: Effects of anaesthesia on noradrenaline kinetics","volume":"80","author":"Maignan","year":"2000","journal-title":"J. Auton. Nerv. Syst."},{"key":"2022041307412115700_BIO058999C22","first-page":"3","article-title":"Fetal hepatic function: the disposition of propranolol in the pregnant sheep","volume":"32","author":"Marshall","year":"1981","journal-title":"Res. Commun. Chem. Pathol. Pharmacol."},{"key":"2022041307412115700_BIO058999C23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0145672","article-title":"Quantifying the interactions between maternal and fetal heart rates by transfer entropy","volume":"10","author":"Marzbanrad","year":"2015","journal-title":"PLoS ONE"},{"key":"2022041307412115700_BIO058999C24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fphys.2018.00478","article-title":"Relationship between short term variability (STV) and onset of cerebral hemorrhage at Ischemia\u2013Reperfusion load in fetal growth restricted (FGR) mice","volume":"9","author":"Minato","year":"2018","journal-title":"Front. Physiol."},{"key":"2022041307412115700_BIO058999C25","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.expneurol.2006.07.027","article-title":"Sarin produces delayed cardiac and central autonomic changes","volume":"203","author":"Morris","year":"2007","journal-title":"Exp. Neurol."},{"key":"2022041307412115700_BIO058999C26","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1213\/00000539-198110000-00002","article-title":"Atropine and glycopyrrolate: hernodynamic effects and placental transfer in the pregnant ewe","volume":"60","author":"Murad","year":"1981","journal-title":"Anesth. Analg."},{"key":"2022041307412115700_BIO058999C27","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1111\/j.1469-185X.2007.00027.x","article-title":"Effect size, confidence interval and statistical significance: A practical guide for biologists","volume":"82","author":"Nakagawa","year":"2007","journal-title":"Biol. Rev."},{"key":"2022041307412115700_BIO058999C28","doi-asserted-by":"publisher","first-page":"11","DOI":"10.7600\/jpfsm.3.11","article-title":"Cardiolocomotor phase synchronization during rhythmic exercise","volume":"3","author":"Niizeki","year":"2014","journal-title":"J. Phys. Fit. Sport. Med."},{"key":"2022041307412115700_BIO058999C29","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1007\/BF00561745","article-title":"Placental transfer of atropine at the end of pregnancy","volume":"15","author":"Onnen","year":"1979","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"2022041307412115700_BIO058999C30","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1098\/rsta.2008.0277","article-title":"Testing foetal\u2013maternal heart rate synchronization via model-based analyses","volume":"367","author":"Riedl","year":"2009","journal-title":"Philos. Trans. R. Soc. A Math. Phys. Eng. Sci."},{"key":"2022041307412115700_BIO058999C31","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1161\/01.RES.78.3.349","article-title":"Mouse mutants and cardiac development: new molecular insights into cardiogenesis","volume":"78","author":"Rossant","year":"1996","journal-title":"Circ. Res."},{"key":"2022041307412115700_BIO058999C32","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/0014-2999(79)90160-2","article-title":"Cardiovascular and respiratory effects of some anesthetics in the decerebrate rat","volume":"53","author":"Sapru","year":"1979","journal-title":"Eur. J. Pharmacol."},{"key":"2022041307412115700_BIO058999C33","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/0002-9378(88)90491-7","article-title":"Placental transfer of \u03b2-adrenergic antagonists studied in an in vitro perfusion system of human placental tissue","volume":"159","author":"Schneider","year":"1988","journal-title":"Am. J. Obstet. Gynecol."},{"key":"2022041307412115700_BIO058999C34","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1007\/s004290050336","article-title":"Nitrergic and peptidergic innervation in the developing rat heart","volume":"201","author":"Shoba","year":"2000","journal-title":"Anat. Embryol. (Berl)."},{"key":"2022041307412115700_BIO058999C35","doi-asserted-by":"publisher","first-page":"bio029512","DOI":"10.1242\/bio.029512","article-title":"Cardiac-enriched BAF chromatin-remodeling complex subunit Baf6\u00b0c regulates gene expression programs essential for heart development and function","volume":"7","author":"Sun","year":"2018","journal-title":"Biol. Open"},{"key":"2022041307412115700_BIO058999C36","doi-asserted-by":"publisher","first-page":"72","DOI":"10.14712\/23362936.2014.25","article-title":"Autonomic nervous system under ketamine\/xylazine and pentobarbital anaesthesia in a Wistar rat model: a chronobiological riew","volume":"114","author":"\u0160vorc","year":"2013","journal-title":"Prague Med. Rep."},{"key":"2022041307412115700_BIO058999C37","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1097\/00005344-200308000-00005","article-title":"Assessment of cardiac function by echocardiography in conscious and anesthetized mice","volume":"42","author":"Tan","year":"2003","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"2022041307412115700_BIO058999C38","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1161\/01.CIR.93.5.1043","article-title":"Heart rate variability: Standards of measurement, physiological interpretation, and clinical use","volume":"93","author":"Task Force of the European Society Organization Electrophysiology","year":"1996","journal-title":"Circulation"},{"key":"2022041307412115700_BIO058999C39","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1097\/AOG.0000000000002042","article-title":"Committee opinion no. 700: Methods for estimating the due date","volume":"129","author":"The American College of Obstetricians and Gynecologists","year":"2017","journal-title":"Obstet. Gynecol."},{"key":"2022041307412115700_BIO058999C40","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1038\/374643a0","article-title":"Noradrenaline is essential for mouse fetal development","volume":"374","author":"Thomas","year":"1995","journal-title":"Nature"},{"key":"2022041307412115700_BIO058999C41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1472-6793-3-2","article-title":"Is there evidence of fetal-maternal heart rate synchronization?","volume":"3","author":"Van Leeuwen","year":"2003","journal-title":"BMC Physiol."},{"key":"2022041307412115700_BIO058999C42","doi-asserted-by":"publisher","first-page":"13661","DOI":"10.1073\/pnas.0901049106","article-title":"Influence of paced maternal breathing on fetal-maternal heart rate coordination","volume":"106","author":"Van Leeuwen","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2022041307412115700_BIO058999C43","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.autneu.2013.01.005","article-title":"Heart rate variability in the individual fetus","volume":"178","author":"Van Leeuwen","year":"2013","journal-title":"Auton. Neurosci. Basic Clin."},{"key":"2022041307412115700_BIO058999C44","doi-asserted-by":"publisher","first-page":"e106036","DOI":"10.1371\/journal.pone.0106036","article-title":"Aerobic exercise during pregnancy and presence of fetal-maternal heart rate synchronization","volume":"9","author":"Van Leeuwen","year":"2014","journal-title":"PLoS ONE"},{"key":"2022041307412115700_BIO058999C45","doi-asserted-by":"publisher","first-page":"28","DOI":"10.3390\/jcdd3030028","article-title":"Part and parcel of the cardiac autonomic nerve system: Unravelling its cellular building blocks during development","volume":"3","author":"V\u00e9gh","year":"2016","journal-title":"J. Cardiovasc. Dev. Dis."},{"key":"2022041307412115700_BIO058999C46","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/0041-008X(90)90359-3","article-title":"Placental and blood-brain barrier transfer following prenatal and postnatal exposures to neuroactive drugs: Relationship with partition coefficient and behavioral teratogenesis","volume":"105","author":"Watanabe","year":"1990","journal-title":"Toxicol. Appl. Pharmacol."}],"container-title":["Biology Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.logists.com\/bio\/bio\/article-pdf\/doi\/10.1242\/bio.058999\/2131834\/bio058999.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.logists.com\/bio\/bio\/article-pdf\/doi\/10.1242\/bio.058999\/2140156\/bio058999.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.logists.com\/bio\/bio\/article-pdf\/doi\/10.1242\/bio.058999\/2140156\/bio058999.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T07:41:42Z","timestamp":1649835702000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/bio\/article\/11\/4\/bio058999\/275036\/Investigating-the-effect-of-cholinergic-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,13]]},"references-count":46,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,4,15]]}},"URL":"https:\/\/doi.org\/10.1242\/bio.058999","relation":{},"ISSN":["2046-6390"],"issn-type":[{"value":"2046-6390","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,13]]},"article-number":"bio058999"}}