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To investigate the mechanisms by which increased levels of Met as hydroxyl-Met (OHMet) improve placental function, forty sows were divided into four groups and fed either a control diet, or diets supplemented with 0.15% OHMet, 0.3% OHMet or 0.3%\u00a0Met (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910). Placentas were collected immediately after expulsion, and extracted proteins were analyzed by tandem mass tag based quantitative proteomic analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that 0.15% OHMet consumption significantly increased placental vascular density compared with the control. Proteomic analysis identified 5,136 proteins, 87 of these were differentially expressed (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05, |fold change|\u00a0&gt;\u20091.2). Enriched pathways in the Kyoto Encyclopedia of Genes and Genomes for 0.15% OHMet vs. control and 0.15% OHMet vs. 0.3% OHMet were glutathione metabolism; for 0.15%\u00a0OHMet vs. 0.3%\u00a0Met, they were NOD-like receptor signaling and apoptosis. Further analysis revealed that 0.15% OHMet supplementation upregulated the protein expression of glutathione-\n                      <jats:italic>S<\/jats:italic>\n                      -transferase (GSTT1) in placentas and trophoblast cells compared with the control and 0.3% OHMet groups, upregulated thioredoxin (TXN) in placentas and trophoblast cells compared with the 0.3% OHMet and 0.3% Met groups, and decreased reactive oxygen species (ROS) levels in trophoblast cells compared with other groups. In contrast, sows fed 0.3% OHMet or 0.3% Met diets increased placental interleukin 1\u03b2 levels compared with the control, and upregulated the protein expression of complex I-B9 (NDUFA3) compared with the 0.15% OHMet group. Furthermore, homocysteine, an intermediate in the trans-sulphuration pathway of Met, damaged placental function by inhibiting the protein expression of TXN, leading to apoptosis and ROS production.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Although dietary 0.15% OHMet supplementation improved placental angiogenesis and increased antioxidative capacity, 0.3% OHMet or 0.3% Met supplementation impaired placental function by aggravating inflammation and oxidative stress, which is associated with cumulative homocysteine levels.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40104-025-01159-z","type":"journal-article","created":{"date-parts":[[2025,3,8]],"date-time":"2025-03-08T19:02:56Z","timestamp":1741460576000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Increased maternal consumption of methionine as its hydroxyl analog improves placental angiogenesis and antioxidative capacity in sows"],"prefix":"10.1186","volume":"16","author":[{"given":"Rui","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiqiang","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lunxiang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Mercier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lun","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengyu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianqiang","family":"Che","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1844-194X","authenticated-orcid":false,"given":"Zhengfeng","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,9]]},"reference":[{"key":"1159_CR1","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/s40104-021-00609-8","volume":"12","author":"S Huang","year":"2021","unstructured":"Huang S, Wu Z, Huang Z, Hao X, Zhang L, Hu C, et al. 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