{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:36:24Z","timestamp":1780637784531,"version":"3.54.1"},"reference-count":44,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["PSI2017-86847-C2-1-R"],"award-info":[{"award-number":["PSI2017-86847-C2-1-R"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["PSI2017-86847-C2-2-R"],"award-info":[{"award-number":["PSI2017-86847-C2-2-R"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Background: In recent years, ultrasonic vocalizations (USV) in pups has become established as a good tool for evaluating behaviors related to communication deficits and emotional states observed in autism spectrum disorder (ASD). Prenatal valproic acid (VPA) exposure leads to impairments and social behavior deficits associated with autism, with the effects of VPA being considered as a reliable animal model of ASD. Some studies also suggest that prenatal exposure to chlorpyrifos (CPF) could enhance autistic-like behaviors. Methods: In order to explore these similarities, in the present study we tested whether prenatal exposure to CPF at GD12.5\u201314.5 produces effects that are comparable to those produced by prenatal VPA exposure at GD12.5 in infant Wistar rats. Using Deep Squeek software, we evaluated total number of USVs, latency to the first call, mean call duration, principal frequency peak, high frequency peak, and type of calls. Results: Consistent with our hypothesis, we found that exposure to both CPF and VPA leads to a significantly smaller number of calls along with a longer latency to produce the first call. No significant effects were found for the remaining dependent variables. Conclusions: These results suggest that prenatal exposure to CPF could produce certain behaviors that are reminiscent of those observed in ASD patients.<\/jats:p>","DOI":"10.3390\/ijerph17176376","type":"journal-article","created":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T08:53:43Z","timestamp":1598950423000},"page":"6376","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Similarities between the Effects of Prenatal Chlorpyrifos and Valproic Acid on Ultrasonic Vocalization in Infant Wistar Rats"],"prefix":"10.3390","volume":"17","author":[{"given":"Miguel","family":"Morales-Navas","sequence":"first","affiliation":[{"name":"Department of Psychology and Health Research Center, University of Almer\u00eda, Ctra. Sacramento, s\/n, 04120 Almer\u00eda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4571-769X","authenticated-orcid":false,"given":"Sergio","family":"Casta\u00f1o-Casta\u00f1o","sequence":"additional","affiliation":[{"name":"Department of Psychology and Health Research Center, University of Almer\u00eda, Ctra. Sacramento, s\/n, 04120 Almer\u00eda, Spain"},{"name":"Department of Health Sciences, Universidad Europea del Atl\u00e1ntico, Calle Isabel Torres, 21, 39011 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"P\u00e9rez-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Psychology and Health Research Center, University of Almer\u00eda, Ctra. Sacramento, s\/n, 04120 Almer\u00eda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ainhoa","family":"S\u00e1nchez-Gil","sequence":"additional","affiliation":[{"name":"Department of Psychology and Health Research Center, University of Almer\u00eda, Ctra. Sacramento, s\/n, 04120 Almer\u00eda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5619-4874","authenticated-orcid":false,"given":"Mar\u00eda","family":"Teresa Colomina","sequence":"additional","affiliation":[{"name":"Department of Psychology and Research Center for Behavior Assessment (CRAMC), Universitat Rovira i Virgili, C\/Carretera de Valls, s\/n, 43007 Tarragona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2878-3791","authenticated-orcid":false,"given":"Xavier","family":"Leinekugel","sequence":"additional","affiliation":[{"name":"Institut de Neurobiologie de la Mediterran\u00e9e (INMED), INSERM UMR1249, Aix-Marseille University, Parc Scientifique de Luminy BP.13, CEDEX 09, 13273 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2190-2006","authenticated-orcid":false,"given":"Fernando","family":"S\u00e1nchez-Santed","sequence":"additional","affiliation":[{"name":"Department of Psychology and Health Research Center, University of Almer\u00eda, Ctra. Sacramento, s\/n, 04120 Almer\u00eda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1007\/BF00632534","article-title":"Ultraschall-Laute bei jungen M\u00e4usen","volume":"43","author":"Zippelius","year":"1956","journal-title":"Naturwissenschaften"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13483","DOI":"10.1038\/s41598-017-13518-6","article-title":"Understanding pup affective state through ethologically significant ultrasonic vocalization frequency","volume":"7","author":"Bertolus","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1002\/aur.1244","article-title":"Atypical Cry Acoustics in 6-Month-Old Infants at Risk for Autism Spectrum Disorder","volume":"5","author":"Sheinkopf","year":"2012","journal-title":"Autism Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/pcn.12860","article-title":"Autism spectrum disorder: Trends in research exploring etiopathogenesis","volume":"73","author":"Gyawali","year":"2019","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s40474-013-0002-2","article-title":"Environmental Factors in the Onset of Autism Spectrum Disorder","volume":"1","author":"Persico","year":"2014","journal-title":"Curr. Dev. Disord. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"285","DOI":"10.5607\/en.2015.24.4.285","article-title":"Exploring the Validity of Valproic Acid Animal Model of Autism","volume":"24","author":"Mabunga","year":"2015","journal-title":"Exp. Neurobiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.neulet.2014.09.039","article-title":"Resveratrol prevents social deficts in animal model of autism induced by valproic acid","volume":"583","author":"Zanatta","year":"2014","journal-title":"Neurosci. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/sj.npp.1300518","article-title":"Behavioral Alterations in Rats Prenatally Exposed to Valproic Acid: Animal Model of Autism","volume":"30","author":"Schneider","year":"2005","journal-title":"Neuropsychopharmacology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainresbull.2014.08.001","article-title":"d-Cycloserine ameliorates social alterations that result from prenatal exposure to valproic acid","volume":"108","author":"Wellmann","year":"2014","journal-title":"Brain Res. Bull."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1289\/ehp.1307044","article-title":"Neurodevelopmental Disorders and Prenatal Residential Proximity to Agricultural Pesticides: The CHARGE Study","volume":"122","author":"Shelton","year":"2014","journal-title":"Environ. Health Perspect."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Giesy, J.P., and Solomon, K.R. (2014). Ecological Risk Assessment for Chlorpyrifos in Terrestrial and Aquatic Systems in the United States, Springer International Publishing.","DOI":"10.1007\/978-3-319-03865-0"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/10408440802272158","article-title":"Review of the Toxicology of Chlorpyrifos With an Emphasis on Human Exposure and Neurodevelopment","volume":"38","author":"Eaton","year":"2008","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1186\/1476-069X-11-S1-S5","article-title":"Chlorpyrifos and neurodevelopmental effects: A literature review and expert elicitation on research and policy","volume":"11","author":"Saunders","year":"2012","journal-title":"Environ. Health"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1289\/ehp.10168","article-title":"Maternal Residence Near Agricultural Pesticide Applications and Autism Spectrum Disorders among Children in the California Central Valley","volume":"115","author":"Roberts","year":"2007","journal-title":"Environ. Health Perspect."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"523","DOI":"10.3109\/10408444.2014.907772","article-title":"Gestational\/Perinatal chlorpyrifos exposure is not associated with autistic-like behaviors in rodents","volume":"44","author":"Williams","year":"2014","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s12940-017-0251-3","article-title":"Prenatal chlorpyrifos leads to autism-like deficits in C57Bl6\/J mice","volume":"16","author":"Lan","year":"2017","journal-title":"Environ. Health"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1476-069X-8-12","article-title":"Prenatal chlorpyrifos exposure alters motor behavior and ultrasonic vocalization in cd-1 mouse pups","volume":"8","author":"Venerosi","year":"2009","journal-title":"Environ. Health"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12940-015-0019-6","article-title":"Effects of maternal chlorpyrifos diet on social investigation and brain neuroendocrine markers in the offspring\u2014A mouse study","volume":"14","author":"Venerosi","year":"2015","journal-title":"Environ. Health"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.neulet.2017.01.053","article-title":"Chlorpyrifos induces anxiety-like behavior in offspring rats exposed during pregnancy","volume":"641","author":"Boareto","year":"2017","journal-title":"Neurosci. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.pbb.2016.12.008","article-title":"Chronic postnatal monoamine oxidase inhibition affects affiliative behavior in rat pupso","volume":"153","author":"Blazevic","year":"2017","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hofer, M.A., Shair, H.N., and Brunelli, S.A. (2001). Ultrasonic Vocalizations in Rat and Mouse Pups. Curr. Protoc. Neurosci., 17.","DOI":"10.1002\/0471142301.ns0814s17"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1037\/0735-7044.122.2.310","article-title":"Maternal care, isolation-induced infant ultrasonic calling, and their relations to adult anxiety-related behavior in the rat","volume":"122","author":"Schwarting","year":"2008","journal-title":"Behav. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1002\/aur.1925","article-title":"Developmental social communication deficits in the Shank3 rat model of phelan-mcdermid syndrome and autism spectrum disorder","volume":"11","author":"Berg","year":"2018","journal-title":"Autism Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00213-010-1859-y","article-title":"Identification of multiple call categories within the rich repertoire of adult rat 50-kHz ultrasonic vocalizations: Effects of amphetamine and social context","volume":"211","author":"Wright","year":"2010","journal-title":"Psychopharmacology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1038\/s41386-018-0303-6","article-title":"DeepSqueak: A deep learning-based system for detection and analysis of ultrasonic vocalizations","volume":"44","author":"Coffey","year":"2019","journal-title":"Neuropsychopharmacology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1109\/TPAMI.2016.2577031","article-title":"Faster R-CNN: Towards Real-Time Object Detection with Region Proposal Networks","volume":"39","author":"Ren","year":"2017","journal-title":"IEEE Trans. Pattern Anal. Mach. Intell."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/0006-2952(61)90145-9","article-title":"A new and rapid colorimetric determination of acetylcholinesterase activity","volume":"7","author":"Ellman","year":"1961","journal-title":"Biochem. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/npp.2014.147","article-title":"Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn","volume":"40","author":"Ross","year":"2014","journal-title":"Neuropsychopharmacology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1006\/faat.1996.0013","article-title":"Evaluation of the developmental and reproductive toxicity of chlorpyrifos in the rat","volume":"29","author":"Breslin","year":"1996","journal-title":"Fundam. Appl. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/j.biopsych.2010.09.031","article-title":"Validating \u03b3 Oscillations and Delayed Auditory Responses as Translational Biomarkers of Autism","volume":"68","author":"Gandal","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1126\/science.1247190","article-title":"Oxytocin-Mediated GABA Inhibition During Delivery Attenuates Autism Pathogenesis in Rodent Offspring","volume":"343","author":"Tyzio","year":"2014","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zieminska, E., Toczy\u0142owska, B., Diamandakis, D., Hilgier, W., Filipkowski, R.K., Polowy, R., Orzel, J., Gorka, M., and Lazarewicz, J.W. (2018). Glutamate, Glutamine and GABA Levels in Rat Brain Measured Using MRS, HPLC and NMR Methods in Study of Two Models of Autism. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00418"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8100","DOI":"10.1038\/s41598-019-44221-3","article-title":"Quantifying ultrasonic mouse vocalizations using acoustic analysis in a supervised statistical machine learning framework","volume":"9","author":"Vogel","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"047012","DOI":"10.1289\/EHP2580","article-title":"Prenatal Organophosphate Pesticide Exposure and Traits Related to Autism Spectrum Disorders in a Population Living in Proximity to Agriculture","volume":"126","author":"Sagiv","year":"2018","journal-title":"Environ. Health Perspect."},{"key":"ref_35","first-page":"28","article-title":"Types and functions of ultrasonic vocalizations in laboratory rats and mice","volume":"46","author":"Portfors","year":"2007","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1093\/icb\/19.2.513","article-title":"Strain Differences in the Ultrasonic Behavior of Rats (Rattus Norvegicus)","volume":"19","author":"Sales","year":"1979","journal-title":"Am. Zool."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.physbeh.2007.11.031","article-title":"Effects of experience and context on 50-kHz vocalizations in rats","volume":"93","author":"Houx","year":"2008","journal-title":"Physiol. Behav."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"219","DOI":"10.3922\/j.psns.2009.2.015","article-title":"Strain and sex differences in fear conditioning: 22 kHz ultrasonic vocalizations and freezing in rats","volume":"2","author":"Graham","year":"2009","journal-title":"Psychol. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Hill, A.P., Zuckerman, K., and Fombonne, E. (2015). Epidemiology of Autism Spectrum Disorders. Translational Approaches to Autism Spectrum Disorder, Springer International Publishing.","DOI":"10.1002\/9781118911389.hautc03"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jped.2016.09.002","article-title":"Autism in 2016: The need for answers","volume":"93","author":"Posar","year":"2017","journal-title":"J. Pediatr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.devbrainres.2003.12.004","article-title":"Morphologic effects of subtoxic neonatal chlorpyrifos exposure in developing rat brain: Regionally selective alterations in neurons and glia","volume":"148","author":"Roy","year":"2004","journal-title":"Dev. Brain Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1124\/mol.111.072314","article-title":"Valproic Acid Increases Formation of Reactive Oxygen Species and Induces Apoptosis in Postimplantation Embryos: A Role for Oxidative Stress in Valproic Acid-Induced Neural Tube Defects","volume":"80","author":"Tung","year":"2011","journal-title":"Mol. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1289\/ehp.7968","article-title":"Alterations in Central Nervous System Serotonergic and Dopaminergic Synaptic Activity in Adulthood after Prenatal or Neonatal Chlorpyrifos Exposure","volume":"113","author":"Aldridge","year":"2005","journal-title":"Environ. Health Perspect."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.ijdevneu.2013.01.006","article-title":"The effects of prenatal exposure to valproic acid on the initial development of serotonergic neurons","volume":"31","author":"Oyabu","year":"2013","journal-title":"Int. J. Dev. Neurosci."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/17\/17\/6376\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:05:38Z","timestamp":1760177138000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/17\/17\/6376"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,1]]},"references-count":44,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["ijerph17176376"],"URL":"https:\/\/doi.org\/10.3390\/ijerph17176376","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,1]]}}}