{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T20:57:00Z","timestamp":1779310620599,"version":"3.51.4"},"reference-count":53,"publisher":"American Society for Clinical Investigation","issue":"13","license":[{"start":{"date-parts":[[2018,7,12]],"date-time":"2018-07-12T00:00:00Z","timestamp":1531353600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Council","award":["G1100221"],"award-info":[{"award-number":["G1100221"]}]},{"name":"Medical Research Council","award":["MRC_MC_UU_12012\/4"],"award-info":[{"award-number":["MRC_MC_UU_12012\/4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,7,12]]},"abstract":"<jats:p>\n                    Preeclampsia and fetal growth restriction (FGR) are major causes of the more than 5 million perinatal and infant deaths occurring globally each year, and both are associated with placental dysfunction. The risk of perinatal and infant death is greater in males, but the mechanisms are unclear. We studied data and biological samples from the Pregnancy Outcome Prediction (POP) study, a prospective cohort study that followed 4,212 women having first pregnancies from their dating ultrasound scan through delivery. We tested the hypothesis that fetal sex would be associated with altered placental function using multiomic and targeted analyses. We found that spermine synthase (\n                    <jats:italic>SMS<\/jats:italic>\n                    ) escapes X-chromosome inactivation (XCI) in the placenta and is expressed at lower levels in male primary trophoblast cells, and male cells were more sensitive to polyamine depletion. The spermine metabolite N1,N12-diacetylspermine (DiAcSpm) was higher in the female placenta and in the serum of women pregnant with a female fetus. Higher maternal serum levels of DiAcSpm increased the risk of preeclampsia but decreased the risk of FGR. To our knowledge, DiAcSpm is the first maternal biomarker to demonstrate opposite associations with preeclampsia and FGR, and this is the first evidence to implicate polyamine metabolism in sex-related differences in placentally related complications of human pregnancy.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.120723","type":"journal-article","created":{"date-parts":[[2018,7,11]],"date-time":"2018-07-11T11:01:22Z","timestamp":1531306882000},"source":"Crossref","is-referenced-by-count":72,"title":["Placental polyamine metabolism differs by fetal sex, fetal growth restriction, and preeclampsia"],"prefix":"10.1172","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5796-4423","authenticated-orcid":true,"given":"Sungsam","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, NIHR Cambridge Comprehensive Biomedical Research Centre,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0799-1105","authenticated-orcid":true,"given":"Ulla","family":"Sovio","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, NIHR Cambridge Comprehensive Biomedical Research Centre,"},{"name":"Centre for Trophoblast Research (CTR), Department of Physiology, Development and Neuroscience,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irving L.M.H.","family":"Aye","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, NIHR Cambridge Comprehensive Biomedical Research Centre,"},{"name":"Centre for Trophoblast Research (CTR), Department of Physiology, Development and Neuroscience,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7178-8921","authenticated-orcid":true,"given":"Francesca","family":"Gaccioli","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, NIHR Cambridge Comprehensive Biomedical Research Centre,"},{"name":"Centre for Trophoblast Research (CTR), Department of Physiology, Development and Neuroscience,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justyna","family":"Dopierala","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, NIHR Cambridge Comprehensive Biomedical Research Centre,"},{"name":"Centre for Trophoblast Research (CTR), Department of Physiology, Development and Neuroscience,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle D.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, NIHR Cambridge Comprehensive Biomedical Research Centre,"},{"name":"Centre for Trophoblast Research (CTR), Department of Physiology, Development and Neuroscience,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela M.","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary Care,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, NIHR Cambridge Comprehensive Biomedical Research Centre,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin J.","family":"Jenkins","sequence":"additional","affiliation":[{"name":"NIHR BRC Core Metabolomics and Lipidomics Laboratory, University of Cambridge, Cambridge, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9998-051X","authenticated-orcid":true,"given":"Albert","family":"Koulman","sequence":"additional","affiliation":[{"name":"NIHR BRC Core Metabolomics and Lipidomics Laboratory, University of Cambridge, Cambridge, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Robert A.","family":"Casero","sequence":"additional","affiliation":[{"name":"The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Const\u00e2ncia","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, NIHR Cambridge Comprehensive Biomedical Research Centre,"},{"name":"Centre for Trophoblast Research (CTR), Department of Physiology, Development and Neuroscience,"},{"name":"University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2936-4890","authenticated-orcid":true,"given":"D. 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