{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:45:21Z","timestamp":1788371121072,"version":"build-2803163510"},"reference-count":106,"publisher":"Oxford University Press (OUP)","issue":"19","license":[{"start":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T00:00:00Z","timestamp":1623110400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["19100-BV19108003"],"award-info":[{"award-number":["19100-BV19108003"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/P002307\/1"],"award-info":[{"award-number":["BB\/P002307\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/P008623\/1"],"award-info":[{"award-number":["BB\/P008623\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Abnormally elevated expression of the imprinted PHLDA2 gene has been reported in the placenta of human babies that are growth restricted in utero in several studies. We previously modelled this gene alteration in mice and found that just 2-fold increased expression of Phlda2 resulted in placental endocrine insufficiency. In addition, elevated Phlda2 was found to drive fetal growth restriction (FGR) of transgenic offspring and impaired maternal care by their wildtype mothers. Being born small and being exposed to suboptimal maternal care have both been associated with the increased risk of mental health disorders in human populations. In the current study we probed behavioural consequences of elevated Phlda2 for the offspring. We discovered increased anxiety-like behaviours, deficits in cognition and atypical social behaviours, with the greatest impact on male offspring. Subsequent analysis revealed alterations in the transcriptome of the adult offspring hippocampus, hypothalamus and amygdala, regions consistent with these behavioural observations. The inclusion of a group of fully wildtype controls raised in a normal maternal environment allowed us to attribute behavioural and molecular alterations to the adverse maternal environment induced by placental endocrine insufficiency rather than the specific gene change of elevated Phlda2. Our work demonstrates that a highly common alteration reported in human FGR is associated with negative behavioural outcomes later in life. Importantly, we also establish the experimental paradigm that placental endocrine insufficiency can program atypical behaviour in offspring highlighting the under-appreciated role of placental endocrine insufficiency in driving disorders of later life behaviour.<\/jats:p>","DOI":"10.1093\/hmg\/ddab154","type":"journal-article","created":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T20:16:43Z","timestamp":1622665003000},"page":"1863-1880","source":"Crossref","is-referenced-by-count":11,"title":["Placental endocrine insufficiency programs anxiety, deficits in cognition and atypical social behaviour in offspring"],"prefix":"10.1093","volume":"30","author":[{"given":"David J","family":"Harrison","sequence":"first","affiliation":[{"name":"Biomedicine Division, School of Biosciences, Cardiff University, Cardif CF10 3AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo D J","family":"Creeth","sequence":"additional","affiliation":[{"name":"Biomedicine Division, School of Biosciences, Cardiff University, Cardif CF10 3AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah R","family":"Tyson","sequence":"additional","affiliation":[{"name":"Biomedicine Division, School of Biosciences, Cardiff University, Cardif CF10 3AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Boque-Sastre","sequence":"additional","affiliation":[{"name":"Biomedicine Division, School of Biosciences, Cardiff University, Cardif CF10 3AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Hunter","sequence":"additional","affiliation":[{"name":"Biomedicine Division, School of Biosciences, Cardiff University, Cardif CF10 3AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic M","family":"Dwyer","sequence":"additional","affiliation":[{"name":"School of Psychology, Cardiff University, Cardiff CF10 3AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7587-5712","authenticated-orcid":false,"given":"Anthony R","family":"Isles","sequence":"additional","affiliation":[{"name":"Behavioural Genetics Group, MRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff CF24 4HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3827-7617","authenticated-orcid":false,"given":"Rosalind M","family":"John","sequence":"additional","affiliation":[{"name":"Biomedicine Division, School of Biosciences, Cardiff University, Cardif CF10 3AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,6,7]]},"reference":[{"key":"2021091611515443100_ref1","first-page":"490","article-title":"Intrauterine growth restriction","volume":"99","author":"Resnik","year":"2002","journal-title":"Obstet. Gynecol."},{"key":"2021091611515443100_ref2","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1136\/bmj.301.6761.1111","article-title":"The fetal and infant origins of adult disease","volume":"301","author":"Barker","year":"1990","journal-title":"BMJ"},{"key":"2021091611515443100_ref3","volume-title":"Trends Endocrinol Metab"},{"key":"2021091611515443100_ref4","doi-asserted-by":"publisher","volume-title":"Developmental Origins of Health and Disease","year":"2006","DOI":"10.1017\/CBO9780511544699"},{"key":"2021091611515443100_ref5","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.biopsych.2010.05.028","article-title":"Early life programming and neurodevelopmental disorders","volume":"68","author":"Bale","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"2021091611515443100_ref6","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.brainres.2008.07.074","article-title":"Diet and the epigenetic (re)programming of phenotypic differences in behavior","volume":"1237","author":"McGowan","year":"2008","journal-title":"Brain Res."},{"key":"2021091611515443100_ref7","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1111\/jcpp.12779","article-title":"Research review: the role of obstetric and neonatal complications in childhood attention deficit and hyperactivity disorder - a systematic review","volume":"58","author":"Serati","year":"2017","journal-title":"J. Child Psychol. Psychiatry"},{"key":"2021091611515443100_ref8","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1542\/peds.2014-1143","article-title":"Early childhood neurodevelopment after intrauterine growth restriction: a systematic review","volume":"135","author":"Levine","year":"2015","journal-title":"Pediatrics"},{"key":"2021091611515443100_ref9","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1093\/aje\/kwj108","article-title":"Fetal growth and childhood behavioral problems: results from the ALSPAC cohort","volume":"163","author":"Wiles","year":"2006","journal-title":"Am. J. Epidemiol."},{"key":"2021091611515443100_ref10","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1017\/S0033291714001998","article-title":"Late preterm birth, post-term birth, and abnormal fetal growth as risk factors for severe mental disorders from early to late adulthood","volume":"45","author":"Lahti","year":"2015","journal-title":"Psychol. Med."},{"key":"2021091611515443100_ref11","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.placenta.2005.07.004","article-title":"Unbalanced placental expression of imprinted genes in human intrauterine growth restriction","volume":"27","author":"McMinn","year":"2006","journal-title":"Placenta"},{"key":"2021091611515443100_ref12","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s00109-006-0131-8","article-title":"Elevated placental expression of the imprinted PHLDA2 gene is associated with low birth weight","volume":"85","author":"Apostolidou","year":"2007","journal-title":"J. Mol. Med."},{"key":"2021091611515443100_ref13","doi-asserted-by":"crossref","first-page":"444","DOI":"10.4161\/epi.5.5.12118","article-title":"Gene expression pattern of IGF2, PHLDA2, PEG10 and CDKN1C imprinted genes in spontaneous miscarriages or fetal deaths","volume":"5","author":"Doria","year":"2010","journal-title":"Epigenetics"},{"key":"2021091611515443100_ref14","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.bone.2011.11.003","article-title":"Relationship between placental expression of the imprinted PHLDA2 gene, intrauterine skeletal growth and childhood bone mass","volume":"50","author":"Lewis, R.M., Cleal, J.K., Ntani, G., Crozier, S.R., Mahon, P.A., Robinson, S.M., Harvey, N.C., Cooper, C., Inskip, H.M., Godfrey, K.M., Hanson, M.A., the Southampton Women's Survey Study Group and John R.M","year":"2012","journal-title":"Bone"},{"key":"2021091611515443100_ref15","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.ajhg.2012.02.021","article-title":"Maternal inheritance of a promoter variant in the imprinted PHLDA2 gene significantly increases birth weight","volume":"90","author":"Ishida","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"2021091611515443100_ref16","doi-asserted-by":"crossref","DOI":"10.1186\/s12881-016-0279-1","article-title":"Placental PHLDA2 expression is increased in cases of fetal growth restriction following reduced fetal movements","volume":"17","author":"Janssen","year":"2016","journal-title":"BMC Med. Genet."},{"key":"2021091611515443100_ref17","article-title":"Deregulation of imprinted genes expression and epigenetic regulators in placental tissue from intrauterine growth restriction","author":"Canicais","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"2021091611515443100_ref18","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0092-8674(00)81156-3","article-title":"Imprinting and the initiation of gene silencing in the germ line","volume":"93","author":"Surani","year":"1998","journal-title":"Cell"},{"key":"2021091611515443100_ref19","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1007\/s003359901182","article-title":"A novel pleckstrin homology-related gene family defined by Ipl\/Tssc3, TDAG51, and Tih1: tissue-specific expression, chromosomal location, and parental imprinting","volume":"10","author":"Frank","year":"1999","journal-title":"Mamm. Genome"},{"key":"2021091611515443100_ref20","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1093\/hmg\/6.12.2021","article-title":"The IPL gene on chromosome 11p15.5 is imprinted in humans and mice and is similar to TDAG51, implicated in Fas expression and apoptosis","volume":"6","author":"Qian","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"2021091611515443100_ref21","first-page":"459","article-title":"The expression of the imprinted gene Ipl is restricted to extra-embryonic tissues and embryonic lateral mesoderm during early mouse development","volume":"46","author":"Dunwoodie","year":"2002","journal-title":"Int. J. Dev. Biol."},{"key":"2021091611515443100_ref22","doi-asserted-by":"crossref","first-page":"42685","DOI":"10.1074\/jbc.M112.388777","article-title":"The maternally expressed gene Tssc3 regulates the expression of MASH2 transcription factor in mouse trophoblast stem cells through the AKT-Sp1 signaling pathway","volume":"287","author":"Takao","year":"2012","journal-title":"J. Biol. Chem."},{"key":"2021091611515443100_ref23","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.mod.2004.10.003","article-title":"Genomic imprinting of IGF2, p57(KIP2) and PEG1\/MEST in a marsupial, the tammar wallaby","volume":"122","author":"Suzuki","year":"2005","journal-title":"Mech. Dev."},{"key":"2021091611515443100_ref24","doi-asserted-by":"crossref","first-page":"7490","DOI":"10.1073\/pnas.122039999","article-title":"Placental overgrowth in mice lacking the imprinted gene Ipl","volume":"99","author":"Frank","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2021091611515443100_ref25","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/j.mod.2004.05.017","article-title":"Placental growth retardation due to loss of imprinting of Phlda2","volume":"121","author":"Salas","year":"2004","journal-title":"Mech. Dev."},{"key":"2021091611515443100_ref26","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1128\/MCB.00662-09","article-title":"The imprinted Phlda2 gene regulates extraembryonic energy stores","volume":"30","author":"Tunster","year":"2010","journal-title":"Mol. Cell. Biol."},{"key":"2021091611515443100_ref27","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.ydbio.2015.10.015","article-title":"The imprinted Phlda2 gene modulates a major endocrine compartment of the placenta to regulate placental demands for maternal resources","volume":"409","author":"Tunster","year":"2016","journal-title":"Dev. Biol."},{"key":"2021091611515443100_ref28","first-page":"1185","article-title":"Isolating the role of elevated Phlda2 in asymmetric late fetal growth restriction in mice","volume":"7","author":"Tunster","year":"2014","journal-title":"Dis. Model. Mech."},{"key":"2021091611515443100_ref29","doi-asserted-by":"crossref","first-page":"3280","DOI":"10.1002\/dvdy.20981","article-title":"Origin and characteristics of glycogen cells in the developing murine placenta","volume":"235","author":"Coan","year":"2006","journal-title":"Dev. Dyn."},{"key":"2021091611515443100_ref30","doi-asserted-by":"crossref","first-page":"570","DOI":"10.3389\/fendo.2018.00570","article-title":"Regulation of placental development and its impact on Fetal growth-new insights from mouse models","volume":"9","author":"Woods","year":"2018","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"2021091611515443100_ref31","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.3389\/fphys.2018.01091","article-title":"The role of placental hormones in mediating maternal adaptations to support pregnancy and lactation","volume":"9","author":"Napso","year":"2018","journal-title":"Front. Physiol."},{"key":"2021091611515443100_ref32","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41576-019-0169-4","article-title":"Mechanisms of early placental development in mouse and humans","volume":"21","author":"Hemberger","year":"2020","journal-title":"Nat. Rev. Genet."},{"key":"2021091611515443100_ref33","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.rbmo.2012.03.018","article-title":"A placenta for life","volume":"25","author":"John","year":"2012","journal-title":"Reprod. BioMed. Online"},{"key":"2021091611515443100_ref34","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.placenta.2020.03.011","article-title":"The placental programming hypothesis: placental endocrine insufficiency and the co-occurrence of low birth weight and maternal mood disorders","volume":"98","author":"Creeth","year":"2020","journal-title":"Placenta"},{"key":"2021091611515443100_ref35","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1111\/j.1365-2826.2011.02175.x","article-title":"A mother's brain knows","volume":"23","author":"Grattan","year":"2012","journal-title":"J. Neuroendocrinol."},{"key":"2021091611515443100_ref36","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.yfrne.2014.11.007","article-title":"Neuroendocrine regulation of maternal behavior","volume":"36","author":"Bridges","year":"2015","journal-title":"Front. Neuroendocrinol."},{"key":"2021091611515443100_ref37","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.2006599","article-title":"Maternal care boosted by paternal imprinting in mammals","volume":"16","author":"Creeth","year":"2018","journal-title":"PLoS Biol."},{"key":"2021091611515443100_ref38","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":"2021091611515443100_ref39","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0079-6123(08)61521-6","article-title":"The pituitary-adrenal system and the developing brain","volume":"32","author":"Levine","year":"1970","journal-title":"Prog. Brain Res."},{"key":"2021091611515443100_ref40","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.yhbeh.2006.06.016","article-title":"Behavioral profiles and stress-induced corticosteroid secretion in male Wistar rats subjected to short and prolonged periods of maternal separation","volume":"50","author":"Roman","year":"2006","journal-title":"Horm. Behav."},{"key":"2021091611515443100_ref41","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.psyneuen.2010.06.005","article-title":"Social influences on neurobiology and behavior: epigenetic effects during development","volume":"36","author":"Curley","year":"2011","journal-title":"Psychoneuroendocrinology"},{"key":"2021091611515443100_ref42","doi-asserted-by":"crossref","first-page":"2903","DOI":"10.1111\/j.1460-9568.2003.02965.x","article-title":"Maternal care influences neuronal survival in the hippocampus of the rat","volume":"18","author":"Bredy","year":"2003","journal-title":"Eur. J. Neurosci."},{"key":"2021091611515443100_ref43","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1038\/sj.npp.1300237","article-title":"Variations in maternal care alter GABA(A) receptor subunit expression in brain regions associated with fear","volume":"28","author":"Caldji","year":"2003","journal-title":"Neuropsychopharmacology"},{"key":"2021091611515443100_ref44","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.yhbeh.2008.02.013","article-title":"Maternal influences on the sexual behavior and reproductive success of the female rat","volume":"54","author":"Cameron","year":"2008","journal-title":"Horm. Behav."},{"key":"2021091611515443100_ref45","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1146\/annurev.neuro.24.1.1161","article-title":"Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations","volume":"24","author":"Meaney","year":"2001","journal-title":"Annu. Rev. Neurosci."},{"key":"2021091611515443100_ref46","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1002\/dev.21326","article-title":"Postnatal maternal care predicts divergent weaning strategies and the development of social behavior","volume":"57","author":"Franks","year":"2015","journal-title":"Dev. Psychobiol."},{"key":"2021091611515443100_ref47","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuroimage.2019.116493","article-title":"Early life stress and brain function: activity and connectivity associated with processing emotion and reward","volume":"209","author":"Herzberg","year":"2020","journal-title":"NeuroImage"},{"key":"2021091611515443100_ref48","doi-asserted-by":"crossref","first-page":"313","DOI":"10.3389\/fnins.2020.00313","article-title":"Unified Behavioral scoring for preclinical models","volume":"14","author":"Harrison","year":"2020","journal-title":"Front. Neurosci."},{"key":"2021091611515443100_ref49","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.biopsych.2019.10.021","article-title":"Erbin in amygdala Parvalbumin-positive neurons modulates anxiety-like Behaviors","volume":"87","author":"Luo","year":"2020","journal-title":"Biol. Psychiatry"},{"key":"2021091611515443100_ref50","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1089\/ars.2013.5358","article-title":"Secisbp2 is essential for embryonic development and enhances selenoprotein expression","volume":"21","author":"Seeher","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"2021091611515443100_ref51","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.placenta.2014.04.018","article-title":"The significance of elevated placental PHLDA2 in human growth restricted pregnancies","volume":"35","author":"Jensen","year":"2014","journal-title":"Placenta"},{"key":"2021091611515443100_ref52","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.tem.2004.03.002","article-title":"The developmental origins of the metabolic syndrome","volume":"15","author":"Gluckman","year":"2004","journal-title":"Trends Endocrinol. Metab."},{"issue":"130","key":"2021091611515443100_ref53","first-page":"e131","article-title":"Perinatal complications and long-term neurodevelopmental outcome of infants with intrauterine growth restriction","volume":"208","author":"Beckerath","year":"2013","journal-title":"Am. J. Obstet. Gynecol."},{"key":"2021091611515443100_ref54","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.ijdevneu.2012.11.006","article-title":"Gestational overgrowth and undergrowth affect neurodevelopment: similarities and differences from behavior to epigenetics","volume":"31","author":"Grissom","year":"2013","journal-title":"Int. J. Dev. Neurosci."},{"key":"2021091611515443100_ref55","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms3311","article-title":"Placental programming of anxiety in adulthood revealed by Igf2-null models","volume":"4","author":"Mikaelsson","year":"2013","journal-title":"Nat. Commun."},{"key":"2021091611515443100_ref56","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1152\/physrev.00040.2011","article-title":"Evolution of placental function in mammals: the molecular basis of gas and nutrient transfer, hormone secretion, and immune responses","volume":"92","author":"Carter","year":"2012","journal-title":"Physiol. Rev."},{"key":"2021091611515443100_ref57","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1113\/jphysiol.2009.181214","article-title":"Adaptations in placental phenotype support fetal growth during undernutrition of pregnant mice","volume":"588","author":"Coan","year":"2010","journal-title":"J. Physiol."},{"key":"2021091611515443100_ref58","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1095\/biolreprod.112.103218","article-title":"Leptin and the placental response to maternal food restriction during early pregnancy in mice","volume":"87","author":"Schulz","year":"2012","journal-title":"Biol. Reprod."},{"key":"2021091611515443100_ref59","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0152227","article-title":"Chronic protein restriction in mice impacts placental function and maternal body weight before fetal growth","volume":"11","author":"Gonzalez","year":"2016","journal-title":"PLoS One"},{"key":"2021091611515443100_ref60","doi-asserted-by":"crossref","first-page":"591","DOI":"10.2741\/E641","article-title":"Gestational protein restriction affects trophoblast differentiation","volume":"5","author":"Gao","year":"2013","journal-title":"Front. Biosci. (Elite Ed)"},{"key":"2021091611515443100_ref61","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S0143-4004(99)80032-0","article-title":"Differential effects of protein malnutrition in pregnant rats on the expression of placental prolactin-like proteins","volume":"20","author":"Medrano","year":"1999","journal-title":"Placenta"},{"key":"2021091611515443100_ref62","doi-asserted-by":"crossref","first-page":"5557","DOI":"10.1073\/pnas.1000440107","article-title":"Contrasting effects of different maternal diets on sexually dimorphic gene expression in the murine placenta","volume":"107","author":"Mao","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2021091611515443100_ref63","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.ijpara.2015.09.004","article-title":"Expression of growth-related genes in the mouse placenta is influenced by interactions between intestinal nematode (Heligmosomoides bakeri) infection and dietary protein deficiency","volume":"46","author":"Starr","year":"2016","journal-title":"Int. J. Parasitol."},{"key":"2021091611515443100_ref64","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0226735","article-title":"Complex patterns of cell growth in the placenta in normal pregnancy and as adaptations to maternal diet restriction","volume":"15","author":"Eaton","year":"2020","journal-title":"PLoS One"},{"key":"2021091611515443100_ref65","doi-asserted-by":"crossref","first-page":"4642","DOI":"10.1073\/pnas.1919563117","article-title":"Bisphenol A and bisphenol S disruptions of the mouse placenta and potential effects on the placenta-brain axis","volume":"117","author":"Mao","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2021091611515443100_ref66","first-page":"157","article-title":"Effects of chromium (VI) exposure on the placental function and reproduction in rats","volume":"37","author":"Lee","year":"2004","journal-title":"J. Prev. Med. Public Health"},{"key":"2021091611515443100_ref67","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1677\/joe.1.06039","article-title":"Dexamethasone-induced intrauterine growth restriction impacts the placental prolactin family, insulin-like growth factor-II and the Akt signaling pathway","volume":"185","author":"Ain","year":"2005","journal-title":"J. Endocrinol."},{"key":"2021091611515443100_ref68","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.mce.2011.01.009","article-title":"Perfluorooctanoic acid-induced inhibition of placental prolactin-family hormone and fetal growth retardation in mice","volume":"337","author":"Suh","year":"2011","journal-title":"Mol. Cell. Endocrinol."},{"key":"2021091611515443100_ref69","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-35606-x","article-title":"Reduced uteroplacental perfusion pressure (RUPP) causes altered trophoblast differentiation and pericyte reduction in the mouse placenta labyrinth","volume":"8","author":"Natale","year":"2018","journal-title":"Sci. Rep."},{"key":"2021091611515443100_ref70","doi-asserted-by":"crossref","DOI":"10.1111\/jne.12859","article-title":"Obesity and regulation of human placental lactogen production in pregnancy","author":"Cattini","year":"2020","journal-title":"J. Neuroendocrinol."},{"key":"2021091611515443100_ref71","doi-asserted-by":"crossref","DOI":"10.3390\/jcm9041142","article-title":"Placental Lactogen as a marker of maternal obesity, diabetes, and fetal growth abnormalities: current knowledge and clinical perspectives","volume":"9","author":"Sibiak","year":"2020","journal-title":"J. Clin. Med."},{"key":"2021091611515443100_ref72","doi-asserted-by":"crossref","first-page":"2999","DOI":"10.1017\/S0033291716001598","article-title":"Maternal prenatal depression is associated with decreased placental expression of the imprinted gene PEG3","volume":"46","author":"Janssen","year":"2016","journal-title":"Psychol. Med."},{"key":"2021091611515443100_ref73","doi-asserted-by":"crossref","DOI":"10.1016\/j.psyneuen.2020.104655","article-title":"Low serum placental lactogen at term is associated with postnatal symptoms of depression and anxiety in women delivering female infants","volume":"116","author":"Sumption","year":"2020","journal-title":"Psychoneuroendocrinology"},{"key":"2021091611515443100_ref74","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1001\/archpsyc.64.3.338","article-title":"Prediction from low birth weight to female adolescent depression: a test of competing hypotheses","volume":"64","author":"Costello","year":"2007","journal-title":"Arch. Gen. Psychiatry"},{"key":"2021091611515443100_ref75","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1111\/j.1469-7610.2009.02105.x","article-title":"Research review: a new perspective on attention-deficit\/hyperactivity disorder: emotion dysregulation and trait models","volume":"50","author":"Martel","year":"2009","journal-title":"J. Child Psychol. Psychiatry"},{"key":"2021091611515443100_ref76","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1017\/S0140525X00013170","article-title":"Gray's neuropsychology of anxiety: an enquiry into the functions of septohippocampal theories","volume":"5","author":"McNaughton","year":"1982","journal-title":"Behav. Brain Sci."},{"key":"2021091611515443100_ref77","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1002\/hipo.22797","article-title":"The social hippocampus","volume":"28","author":"Montagrin","year":"2018","journal-title":"Hippocampus"},{"key":"2021091611515443100_ref78","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/s41586-018-0416-4","article-title":"5-HT release in nucleus accumbens rescues social deficits in mouse autism model","volume":"560","author":"Walsh","year":"2018","journal-title":"Nature"},{"key":"2021091611515443100_ref79","doi-asserted-by":"crossref","DOI":"10.1038\/s41398-020-0699-8","article-title":"Genetic evidence of gender difference in autism spectrum disorder supports the female-protective effect","volume":"10","author":"Zhang","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"2021091611515443100_ref80","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1111\/j.1471-4159.2005.03073.x","article-title":"Influences of dopaminergic lesion on epidermal growth factor-ErbB signals in Parkinson's disease and its model: neurotrophic implication in nigrostriatal neurons","volume":"93","author":"Iwakura","year":"2005","journal-title":"J. Neurochem."},{"key":"2021091611515443100_ref81","doi-asserted-by":"crossref","DOI":"10.1016\/j.mam.2019.10.003","article-title":"Neurological disorders and mitochondria","volume":"71","author":"Cabral-Costa","year":"2020","journal-title":"Mol. Asp. Med."},{"key":"2021091611515443100_ref82","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3233\/JHD-130061","article-title":"Cognitive deficits in transgenic and knock-in HTT mice parallel those in Huntington's disease","volume":"3","author":"Farrar","year":"2014","journal-title":"J. Huntingtons Dis."},{"key":"2021091611515443100_ref83","first-page":"116","article-title":"Regulation of fear extinction in the basolateral amygdala by dopamine D2 receptors accompanied by altered GluR1, GluR1-Ser845 and NR2B levels","volume":"11","author":"Shi","year":"2017","journal-title":"Front. Behav. Neurosci."},{"key":"2021091611515443100_ref84","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1007\/s11515-017-1455-1","article-title":"The role of dopamine D2 receptors in the amygdala in metabolic and behavioral responses to stress in male Swiss-Webster mice","volume":"12","author":"Hassantash","year":"2017","journal-title":"Front. Biol."},{"key":"2021091611515443100_ref85","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1038\/mp.2015.210","article-title":"Dopamine D2 receptors gate generalization of conditioned threat responses through mTORC1 signaling in the extended amygdala","volume":"21","author":"De Bundel","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"2021091611515443100_ref86","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/0014-4886(73)90187-8","article-title":"Time of neuron origin in mouse hypothalamic nuclei","volume":"41","author":"Shimada","year":"1973","journal-title":"Exp. Neurol."},{"key":"2021091611515443100_ref87","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1126\/science.7777856","article-title":"Linked regularities in the development and evolution of mammalian brains","volume":"268","author":"Finlay","year":"1995","journal-title":"Science"},{"key":"2021091611515443100_ref88","doi-asserted-by":"crossref","first-page":"4959","DOI":"10.1242\/dev.124.24.4959","article-title":"Early specification and autonomous development of cortical fields in the mouse hippocampus","volume":"124","author":"Tole","year":"1997","journal-title":"Development"},{"key":"2021091611515443100_ref89","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/tera.1420160220","article-title":"Correlations between prenatally-induced alterations in CNS cell populations and postnatal function","volume":"16","author":"Rodier","year":"1977","journal-title":"Teratology"},{"key":"2021091611515443100_ref90","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1111\/j.1469-7610.2010.02259.x","article-title":"The effects of maternal postnatal depression and child sex on academic performance at age 16 years: a developmental approach","volume":"51","author":"Murray","year":"2010","journal-title":"J.Child Psychol. Psychiatry"},{"key":"2021091611515443100_ref91","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1192\/bjp.180.6.502","article-title":"Maternal antenatal anxiety and children's behavioural\/emotional problems at 4 years. Report from the Avon longitudinal study of parents and children","volume":"180","author":"O'Connor","year":"2002","journal-title":"Br. J. Psychiatry"},{"key":"2021091611515443100_ref92","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.physbeh.2012.02.011","article-title":"Sex differences in the programming effects of prenatal stress on psychopathology and stress responses: an evolutionary perspective","volume":"106","author":"Glover","year":"2012","journal-title":"Physiol. Behav."},{"key":"2021091611515443100_ref93","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1038\/nmeth.1500","article-title":"Taming anxiety in laboratory mice","volume":"7","author":"Hurst","year":"2010","journal-title":"Nat. Methods"},{"key":"2021091611515443100_ref94","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-20716-3","article-title":"Handling method alters the hedonic value of reward in laboratory mice","volume":"8","author":"Clarkson","year":"2018","journal-title":"Sci. Rep."},{"key":"2021091611515443100_ref95","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1111\/2041-210X.12584","article-title":"BORIS : a free, versatile open-source event-logging software for video\/audio coding and live observations","volume":"7","author":"Friard","year":"2016","journal-title":"Methods Ecol. Evol."},{"key":"2021091611515443100_ref96","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0014-2999(03)01274-3","article-title":"The mouse light\/dark box test","volume":"463","author":"Bourin","year":"2003","journal-title":"Eur. J. Pharmacol."},{"key":"2021091611515443100_ref97","doi-asserted-by":"crossref","first-page":"5515","DOI":"10.1073\/pnas.1703477114","article-title":"Social propinquity in rodents as measured by tube cooccupancy differs between inbred and outbred genotypes","volume":"114","author":"Tuttle","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2021091611515443100_ref98","doi-asserted-by":"publisher","DOI":"10.1002\/0471142301.ns0826s56","article-title":"Automated three-chambered social approach task for mice","author":"Yang","year":"2011","journal-title":"Curr. Protoc. Neurosci"},{"key":"2021091611515443100_ref99","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1016\/S0031-9384(96)00305-8","article-title":"Chronic mild stress and sucrose consumption: validity as a model of depression","volume":"60","author":"Forbes","year":"1996","journal-title":"Physiol. Behav."},{"key":"2021091611515443100_ref100","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1080\/17470218.2011.652969","article-title":"EPS prize lecture. Licking and liking: the assessment of hedonic responses in rodents","volume":"65","author":"Dwyer","year":"2012","journal-title":"Q. J. Exp. Psychol."},{"key":"2021091611515443100_ref101","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: a flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"2021091611515443100_ref102","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"2021091611515443100_ref103","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: an efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"2021091611515443100_ref104","doi-asserted-by":"crossref","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"2021091611515443100_ref105","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/1471-2105-14-128","article-title":"Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool","volume":"14","author":"Chen","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"2021091611515443100_ref106","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: a comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res."}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/hmg\/advance-article-pdf\/doi\/10.1093\/hmg\/ddab154\/38940066\/ddab154.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/hmg\/article-pdf\/30\/19\/1863\/40374180\/ddab154.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/hmg\/article-pdf\/30\/19\/1863\/40374180\/ddab154.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T11:54:41Z","timestamp":1631793281000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/30\/19\/1863\/6294504"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,7]]},"references-count":106,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2021,6,7]]},"published-print":{"date-parts":[[2021,9,15]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddab154","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,10,1]]},"published":{"date-parts":[[2021,6,7]]}}}