{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T10:21:04Z","timestamp":1775384464613,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T00:00:00Z","timestamp":1711324800000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["CIHR PJT\u2010175161"],"award-info":[{"award-number":["CIHR PJT\u2010175161"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Problem<\/jats:title>\n                    <jats:p>Fetal spina bifida (SB) is more common in pregnant people with folate deficiency or anomalies of folate metabolism. It is also known that fetuses with SB have a higher risk of low birthweight, a condition that is typically placental\u2010mediated. We therefore hypothesized that fetal SB would associate with altered expression of key placental folate transporters and an increase in Hofbauer cells (HBCs), which are folate\u2010dependent placental macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method of study<\/jats:title>\n                    <jats:p>\n                      Folate receptor\u2010\u03b1 (FR\u03b1), proton coupled folate receptor (PCFT), and reduced folate carrier (RFC) protein localization and expression (immunohistochemistry) and HBC phenotypes (HBC abundance and folate receptor\u2010\n                      <jats:italic>\u03b2<\/jats:italic>\n                      [\n                      <jats:italic>FR\u03b2<\/jats:italic>\n                      ] expression; RNA in situ hybridization) were assessed in placentae from fetuses with SB (cases;\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a012) and in term (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a010) and gestational age (GA) \u2013 and maternal body mass index \u2013 matched (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a012) controls without congenital anomalies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Cases had a higher proportion of placental villous cells that were HBCs (6.9%\u00a0vs. 2.4%,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.0001) and higher average HBC\n                      <jats:italic>FR\u03b2<\/jats:italic>\n                      expression (3.2 mRNA molecules per HBC vs. 2.3,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.03) than GA\u2010matched controls. HBCs in cases were largely polarized to a regulatory phenotype (median 92.1% of HBCs). In sex\u2010stratified analyses, only male cases had higher HBC levels and HBC\n                      <jats:italic>FR\u03b2<\/jats:italic>\n                      expression than GA\u2010matched controls. There were no differences between groups in the total percent of syncytium and stromal cells that were positive for FR\u03b1, PCFT, or RFC protein immunolabeling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      HBC abundance and\n                      <jats:italic>FR\u03b2<\/jats:italic>\n                      expression by HBCs are increased in placentae of fetuses with SB, suggesting immune\u2010mediated dysregulation in placental phenotype, and could contribute to SB\u2010associated comorbidities.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aji.13836","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T01:13:05Z","timestamp":1711415585000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Altered placental immune cell composition and gene expression with isolated fetal spina bifida"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6717-0723","authenticated-orcid":false,"given":"Marina","family":"White","sequence":"first","affiliation":[{"name":"Department of Health Sciences Carleton University  Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hasan","family":"Abdo","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Carleton University  Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Grynspan","sequence":"additional","affiliation":[{"name":"Vernon Jubilee Hospital  Vernon British Columbia Canada"},{"name":"Department of Pathology and Laboratory Medicine University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim Van","family":"Mieghem","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Sinai Health System  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin L.","family":"Connor","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Carleton University  Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ede.0000257063.77411.e9"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwz040"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/85.1.285S"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201200084"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/83.5.993"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13224\u2010011\u20100092\u2010x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1017\/s0007114509288994"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100035\u20101570379"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.01284"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/bf02724177"},{"issue":"2","key":"e_1_2_9_12_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.2223\/JPED.964","article-title":"Neural tube defects and associated factors in liveborn and stillborn infants","volume":"79","author":"Aguiar MJ","year":"2003","journal-title":"J Pediatr (Rio J)"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2021.08.052"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02628"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12112"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.771054"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1901185"},{"key":"e_1_2_9_18_1","doi-asserted-by":"crossref","unstructured":"WhiteM GrynspanD Arif\u2010PardyJ Van MieghemT ConnorKL Altered placental phenotype and increased risk of placental pathology in fetal spina bifida: a matched case\u2010control study.medRxiv.2023. doi:10.1101\/2023.09.20.23295859","DOI":"10.1101\/2023.09.20.23295859"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.80112"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2018.06.003"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033\u2010019\u201004776\u2010w"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13710"},{"key":"e_1_2_9_23_1","unstructured":"World Health Organization. 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