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However, the relationship of fetal hypHcy with adverse pregnancy outcomes is under\u2010represented. The present study aims to investigate the association of fetal hypHcy with oxidative stress and placental inflammation that can contribute to an early breakdown of maternal\u2010fetal tolerance in pre\u2010term birth (PTB).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cord blood and placenta tissue were collected from PTB and term infant group. Levels of homocysteine, folic acid, vitamin B12 and oxidative stress markers (MDA, T\u2010AOC, 8\u2010OHdG) were measured in cord blood serum using ELISA and respective standard assay kits. Relative expression of candidate genes (TNF\u2010\u03b1, IL\u20106, IL1\u2010\u03b2, VEGF\u2010A, MMP2 and MMP9) was also checked using RT\u2010PCR and immunoblotting\/immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PTB infants showed significantly higher levels of homocysteine (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.02) and lower levels of vitamin B12 (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.005) as compared to term infants. We also found that PTB infants with hypHcy had lower T\u2010AOC (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.003) and higher MDA (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.04) levels as compared to term infants with normal homocysteine levels. The mRNA and protein levels of TNF\u2010\u03b1, VEGF\u2010A, MMP2 and MMP9 were significantly higher in hypHcy PTB infants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results show that fetal hypHcy is associated with oxidative stress and an increase in inflammatory markers in the placenta. Thus, in conclusion, our study demonstrates that fetal hypHcy during pregnancy is a potential risk factor that may initiate an early breakdown of uterine quiescence due to activation of inflammatory processes leading to PTB.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13589","type":"journal-article","created":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T01:54:56Z","timestamp":1656122096000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Fetal hyperhomocysteinemia is associated with placental inflammation and early breakdown of maternal\u2010fetal tolerance in pre\u2010term birth"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0021-8168","authenticated-orcid":false,"given":"Renu","family":"Bala","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics Banaras Hindu University  Varanasi Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachna","family":"Verma","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Banaras Hindu University  Varanasi Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snehil","family":"Budhwar","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Banaras Hindu University  Varanasi Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita","family":"Prakash","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Institute of Medical Sciences Banaras Hindu University  Varanasi Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shikha","family":"Sachan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Institute of Medical Sciences Banaras Hindu University  Varanasi Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60820-4"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.3MR0615-272RR"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioy261"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2007.03.008"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2017.30"},{"issue":"1","key":"e_1_2_8_7_1","first-page":"1","article-title":"Hyperhomocysteinemia: the independent risk factor of cardiovascular diseases","volume":"8","author":"Tanweer A","year":"2020","journal-title":"Adv Life Sci"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)90165-5"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-006-0223-2"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2003.021634"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM.2001.115"},{"issue":"775","key":"e_1_2_8_12_1","first-page":"82","article-title":"Vitamin B12 deficiency and hyperhomocysteinemia in rural and urban Indians","volume":"54","author":"Yajnik C","year":"2006","journal-title":"Japi"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2012.03.003"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1619582114"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-012-9214-8"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-0495(00)80077-3"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/7432797"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2008.04.002"},{"issue":"1","key":"e_1_2_8_19_1","first-page":"77","article-title":"Relationship among TNF\u2010alpha gene promoter\u2010308 site polymorphism, the levels of maternal serum TNF\u2010alpha, and the mRNA expression placental TNF\u2010alpha in preterm labor. 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