{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:39:40Z","timestamp":1790185180052,"version":"4.1.0"},"reference-count":90,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T00:00:00Z","timestamp":1631404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 105-2410-H-037-005"],"award-info":[{"award-number":["MOST 105-2410-H-037-005"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Both the detrimental effect of prenatal exposure to di-(2-ethylhexyl)-phthalate (DEHP) and the beneficial effects of physical exercise on brain functions have been reported. The oxytocin pathway has been implicated in the onset of maternal behaviors. Epigenetic modification of the oxytocin receptor gene (OXTR) through DNA methylation has been associated with the pathogenesis of neuropsychiatric disorders. The purpose of this study was to investigate the effects of prenatal DEHP exposure on oxytocin-regulated maternal behaviors and to examine the protective effect of exercise. Pregnant rats (F0) were fed with vehicle or DEHP during gestation and the offspring females (F1) were assessed for their maternal behaviors by pup retrieval test at postpartum. The results showed that reduced pup retrieval activities without significant alteration of stress responses were observed in the prenatally DEHP-exposed females. Prenatal DEHP exposure decreased the expressions of oxytocin, Oxtr mRNA, and oxytocin receptor, and increased Oxtr methylation in the hypothalamus of postpartum female rats. There were no significant effects of exercise on behavioral, biochemical, and epigenetic measurements. These results suggest that prenatal DEHP exposure has a long-term adverse effect on maternal behaviors; Oxtr hyper-methylation may be a potential epigenetic mechanism for this alteration, which cannot be prevented by physical exercise during childhood.<\/jats:p>","DOI":"10.3390\/ijms22189847","type":"journal-article","created":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T21:45:57Z","timestamp":1631483157000},"page":"9847","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effects of Prenatal Phthalate Exposure and Childhood Exercise on Maternal Behaviors in Female Rats at Postpartum: A Role of Oxtr Methylation in the Hypothalamus"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7470-4233","authenticated-orcid":false,"given":"Yi-Ju","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Sports Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9916-2119","authenticated-orcid":false,"given":"Hwai-Ting","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Ph. D. Program in Biomedical Engineering, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1438-643X","authenticated-orcid":false,"given":"Muhammad Asad","family":"Chaudhary","sequence":"additional","affiliation":[{"name":"Ph. D. Program in Biomedical Engineering, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ching","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Food and Beverage Services, Tainan University of Technology, Tainan 710302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5571-2505","authenticated-orcid":false,"given":"Dean-Chuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1126\/science.1252723","article-title":"The biology of mammalian parenting and its effect on offspring social development","volume":"345","author":"Rilling","year":"2014","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1002\/cad.20170","article-title":"Oxytocin and maternal brain plasticity","volume":"2016","author":"Kim","year":"2016","journal-title":"New Dir. 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