{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:48:51Z","timestamp":1790275731954,"version":"4.1.0"},"reference-count":63,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,10,30]],"date-time":"2012-10-30T00:00:00Z","timestamp":1351555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:sec><jats:title>Scope<\/jats:title><jats:p>Genetic or nutritional disturbances in folate metabolism lead to hyperhomocysteinemia and adverse reproductive outcomes. Folate\u2010dependent homocysteine remethylation is required for methylation reactions and may influence choline\/betaine metabolism. Hyperhomocysteinemia has been suggested to play a role in inflammation. The goal of this study was to determine whether folate\u2010related pregnancy complications could be due to altered expression of some inflammatory mediators or due to disturbances in methylation intermediates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Pregnant mice with or without a deficiency of methylenetetrahydrofolate reductase (<jats:styled-content style=\"fixed-case\">MTHFR<\/jats:styled-content>) were fed control diets or folate\u2010deficient (<jats:styled-content style=\"fixed-case\">FD<\/jats:styled-content>) diets; tissues were collected at embryonic day 14.5. <jats:styled-content style=\"fixed-case\">FD<\/jats:styled-content> decreased plasma phosphocholine and increased plasma glycerophosphocholine and lysophosphatidylcholine. Liver betaine, phosphocholine, and <jats:italic>S<\/jats:italic>\u2010adenosylmethionine:<jats:italic>S<\/jats:italic>\u2010adenosylhomocysteine ratios were reduced in <jats:styled-content style=\"fixed-case\">FD<\/jats:styled-content>. In liver, spleen, and placenta, the lowest levels of apolipoprotein <jats:styled-content style=\"fixed-case\">AI<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>po<jats:styled-content style=\"fixed-case\">AI<\/jats:styled-content>) were observed in <jats:italic>Mthfr<\/jats:italic><jats:sup>+\/\u2013<\/jats:sup> mice fed <jats:styled-content style=\"fixed-case\">FD<\/jats:styled-content>. Increased interferon\u2010gamma (<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b3) was observed in spleen and placentae due to <jats:styled-content style=\"fixed-case\">FD<\/jats:styled-content> or <jats:italic>Mthfr<\/jats:italic> genotype. Plasma homocysteine correlated negatively with liver and spleen <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>po<jats:styled-content style=\"fixed-case\">AI<\/jats:styled-content>, and positively with <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Low dietary folate or <jats:italic>Mthfr<\/jats:italic> deficiency during pregnancy may result in adverse pregnancy outcomes by altering expression of the inflammatory mediators <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>po<jats:styled-content style=\"fixed-case\">AI<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b3 in spleen and placenta. Disturbances in choline metabolism or methylation reactions may also play a role.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.201200152","type":"journal-article","created":{"date-parts":[[2012,10,30]],"date-time":"2012-10-30T12:16:20Z","timestamp":1351599380000},"page":"661-670","source":"Crossref","is-referenced-by-count":24,"title":["Low dietary folate and methylenetetrahydrofolate reductase deficiency may lead to pregnancy complications through modulation of <scp>A<\/scp>po<scp>AI<\/scp> and <scp>IFN<\/scp>\u2010\u03b3 in spleen and placenta, and through reduction of methylation potential"],"prefix":"10.1002","volume":"57","author":[{"given":"Leonie G.","family":"Mikael","sequence":"first","affiliation":[{"name":"Departments of Human Genetics and Pediatrics McGill University, Montreal Children's Hospital Research Institute  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Pancer","sequence":"additional","affiliation":[{"name":"Departments of Human Genetics and Pediatrics McGill University, Montreal Children's Hospital Research Institute  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Division of Nutritional Sciences Cornell University  Ithaca NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Wu","sequence":"additional","affiliation":[{"name":"Departments of Human Genetics and Pediatrics McGill University, Montreal Children's Hospital Research Institute  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Caudill","sequence":"additional","affiliation":[{"name":"Division of Nutritional Sciences Cornell University  Ithaca NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rima","family":"Rozen","sequence":"additional","affiliation":[{"name":"Departments of Human Genetics and Pediatrics McGill University, Montreal Children's Hospital Research Institute  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,10,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0456fje"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/82.1.188"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20575"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1201\/9781420071252-c18"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.5.433"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0595-111"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.93.1.7"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-131-5-199909070-00008"},{"key":"e_1_2_7_10_1","first-page":"326","article-title":"Effect of homocysteine concentration in early pregnancy on gestational hypertensive disorders and other pregnancy outcomes","volume":"54","author":"Dodds L.","year":"2008","journal-title":"Clin. Chem. Lab Med."},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/71.4.962"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1134\/S0006297911040109"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2007.03.008"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM.2003.221"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/00016340701515423"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh169"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2010.00913.x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161210793797933"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.111.151753"},{"key":"e_1_2_7_20_1","first-page":"1841","volume-title":"The metabolic and molecular bases of inherited disease","author":"Havel R. J.","year":"1995"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/hc4401.098467"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306336200"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000154140.73570.00"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000204825.66410.0b"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2009.05.011"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1373\/49.2.286"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac025624x"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.111.138859"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.69.1331"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.110.124917"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(07)96002-2"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.2009.28754"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nu.14.070194.001413"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099-1492(199911)12:7<413::AID-NBM587>3.0.CO;2-U"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj1980565"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1076\/apab.110.5.393.11832"},{"key":"e_1_2_7_37_1","first-page":"435","article-title":"Evidence of saturable uptake mechanisms at maternal and fetal sides of the perfused human placenta by rapid paired\u2010tracer dilution: studies with calcium and choline","volume":"8","author":"Sweiry J. H.","year":"1986","journal-title":"J. Dev. Physiol."},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152412800792706"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M611726200"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-09-3078"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/131.11.2811"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn157"},{"key":"e_1_2_7_43_1","first-page":"223","article-title":"Changes in the thymus, spleen and lymph nodes during pregnancy and lactation in the rat","volume":"118","author":"Mc Lean J. M.","year":"1974","journal-title":"J. Anat."},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1177\/1933719108329095"},{"key":"e_1_2_7_45_1","first-page":"27","article-title":"How your mother tolerated you for nine months","volume":"1","author":"De Lemos M. A.","year":"2003","journal-title":"BioTeach J."},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2009.06.262"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-1113"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11745-002-0981-4"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-06-287243"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1191\/0960327102ht287oa"},{"key":"e_1_2_7_51_1","first-page":"161","article-title":"Effects of TNF, IL\u20101, and the combination of both cytokines on cholesterol metabolism in Syrian hamsters","volume":"13","author":"Hardard\u00f3ttir I.","year":"1994","journal-title":"Lymphokine Cytokine Res."},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2003.08.004"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2010.12.002"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2007.07.191"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0001-6349.2005.00714.x"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-0067"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2011.01.009"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.2174\/157016106777698379"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389201043489657"},{"key":"e_1_2_7_60_1","first-page":"107","article-title":"Circulating homocysteine is an inflammation marker and a risk factor of life\u2010threatening inflammatory diseases","volume":"19","author":"Wu J. T.","year":"2007","journal-title":"J. Biomed. Lab Sci."},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2007.01.008"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.23.13621"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/124.11.2197"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/0955-2863(92)90073-R"}],"container-title":["Molecular Nutrition &amp; Food Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmnfr.201200152","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mnfr.201200152","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T01:22:02Z","timestamp":1694481722000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mnfr.201200152"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,10,30]]},"references-count":63,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,4]]}},"alternative-id":["10.1002\/mnfr.201200152"],"URL":"https:\/\/doi.org\/10.1002\/mnfr.201200152","archive":["Portico"],"relation":{},"ISSN":["1613-4125","1613-4133"],"issn-type":[{"value":"1613-4125","type":"print"},{"value":"1613-4133","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,10,30]]}}}