{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:30:05Z","timestamp":1792816205753,"version":"4.5.0"},"reference-count":64,"publisher":"National Academy of Sciences","issue":"21","license":[{"start":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T00:00:00Z","timestamp":1715817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Government | Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["470608"],"award-info":[{"award-number":["470608"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Canadian Government | Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["DG386445"],"award-info":[{"award-number":["DG386445"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"name":"New Frontiers in Research Fund","award":["NFRF-2018-00597"],"award-info":[{"award-number":["NFRF-2018-00597"]}]},{"DOI":"10.13039\/501100000024","name":"Canadian Government | Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MFE-183073"],"award-info":[{"award-number":["MFE-183073"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,5,21]]},"abstract":"<jats:p>\n                    Arginine vasopressin (AVP) neurons of the hypothalamic paraventricular region (AVP\n                    <jats:sup>PVN<\/jats:sup>\n                    ) mediate sex-biased social behaviors across most species, including mammals. In mice, neural sex differences are thought to be established during a critical window around birth ( embryonic (E) day 18 to postnatal (P) day 2) whereby circulating testosterone from the fetal testis is converted to estrogen in sex-dimorphic brain regions. Here, we found that AVP\n                    <jats:sup>PVN<\/jats:sup>\n                    neurons are sexually dimorphic by E15.5, prior to this critical window, and that gestational bisphenol A (BPA) exposure permanently masculinized female AVP\n                    <jats:sup>PVN<\/jats:sup>\n                    neuronal numbers, projections, and electrophysiological properties, causing them to display male-like phenotypes into adulthood. Moreover, we showed that nearly twice as many neurons that became AVP\n                    <jats:sup>+<\/jats:sup>\n                    by P0 were born at E11 in males and BPA-exposed females compared to control females, suggesting that AVP\n                    <jats:sup>PVN<\/jats:sup>\n                    neuronal masculinization occurs between E11 and P0. We further narrowed this sensitive period to around the timing of neurogenesis by demonstrating that exogenous estrogen exposure from E14.5 to E15.5 masculinized female AVP\n                    <jats:sup>PVN<\/jats:sup>\n                    neuronal numbers, whereas a pan-estrogen receptor antagonist exposed from E13.5 to E15.5 blocked masculinization of males. Finally, we showed that restricting BPA exposure to E7.5-E15.5 caused adult females to display increased social dominance over control females, consistent with an acquisition of male-like behaviors. Our study reveals an E11.5 to E15.5 window of estrogen sensitivity impacting AVP\n                    <jats:sup>PVN<\/jats:sup>\n                    sex differentiation, which is impacted by prenatal BPA exposure.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2313207121","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T12:51:10Z","timestamp":1715863870000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":6,"title":["Hypothalamic vasopressin sex differentiation is observed by embryonic day 15 in mice and is disrupted by the xenoestrogen bisphenol A"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1085-2712","authenticated-orcid":false,"given":"Jing","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary T2N 1N4, Canada"},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary T2N 1N4, Canada"},{"name":"Hotchkiss Brain Institute, University of Calgary, Calgary T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinara","family":"Baimoukhametova","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute, University of Calgary, Calgary T2N 1N4, Canada"},{"name":"Department of Physiology and Pharmacology, University of Calgary, Calgary T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0344-4032","authenticated-orcid":false,"given":"Catherine","family":"Lebel","sequence":"additional","affiliation":[{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary T2N 1N4, Canada"},{"name":"Hotchkiss Brain Institute, University of Calgary, Calgary T2N 1N4, Canada"},{"name":"Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaideep S.","family":"Bains","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute, University of Calgary, Calgary T2N 1N4, Canada"},{"name":"Department of Physiology and Pharmacology, University of Calgary, Calgary T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah M.","family":"Kurrasch","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary T2N 1N4, Canada"},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary T2N 1N4, Canada"},{"name":"Hotchkiss Brain Institute, University of Calgary, Calgary T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,5,16]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1158668"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2005.07.050"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)00402-0"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(81)90989-6"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22635"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2014.00058"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-019-01989-4"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(00)00886-6"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2007.11.063"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI144450"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aau7356"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aat7838"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2007.07.010"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(98)00084-7"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.139.10.6216"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2008.07.014"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.021100703"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2013.08.008"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2011.05.002"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2016.05.040"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/aur.1444"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2016.07.028"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1104492"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2014.10.023"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.adh8488"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1417731112"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abd1159"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1159\/000509421"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2017.00308"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1996.01830020055007"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","unstructured":"S. N. Freda D. Badong L. Xiao Y. Liu Y. Kozorovitskiy Brainwide input-output architecture of paraventricular oxytocin and vasopressin neurons. bioRxiv [Preprint] (2022). https:\/\/doi.org\/10.1101\/2022.01.17.476652 (Accessed 18 January 2022).","DOI":"10.1101\/2022.01.17.476652"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.07.036"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","unstructured":"M. M. McCarthy G. J. De Vries N. G. Forger \u201cSexual differentiation of the brain: A fresh look at mode mechanisms and meaning\u201d in Hormones Brain and Behavior D. Pfaff M. Jo\u00ebls Eds. (Elsevier 2017) vol. 5 pp. 3\u201332.","DOI":"10.1016\/B978-0-12-803592-4.00091-2"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2022.114040"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.t01-1-00193.x"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.901820511"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2610-19.2020"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.61"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-018-0116-4"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2008.06073.x"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1186\/2042-6410-1-8"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-03-01789.1994"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(96)00298-3"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2009.10.002"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(79)90357-1"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.139.3.5788"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(75)90755-6"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-0607"},{"key":"e_1_3_4_49_2","first-page":"1","article-title":"Neurosteroids: Of the nervous system, by the nervous system, for the nervous system","volume":"52","author":"Baulieu E. E.","year":"1997","unstructured":"E. E. Baulieu, Neurosteroids: Of the nervous system, by the nervous system, for the nervous system. Recent Prog. Horm. Res. 52, 1\u201332 (1997).","journal-title":"Recent Prog. Horm. Res."},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00084"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18231-z"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17890-2"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232012288"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-20-09005.2002"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2008.11.001"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201800012"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.12.033"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2011-1335"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6163211"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064943"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1097\/ANA.0b013e318227725f"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2021.03.018"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1213-6"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.10.010"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2313207121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T12:52:54Z","timestamp":1715863974000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2313207121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,16]]},"references-count":64,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2024,5,21]]}},"alternative-id":["10.1073\/pnas.2313207121"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2313207121","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,16]]},"assertion":[{"value":"2023-08-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2313207121"}}