{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T01:20:05Z","timestamp":1789089605516,"version":"build-2803163510"},"reference-count":61,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T00:00:00Z","timestamp":1769212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T00:00:00Z","timestamp":1769212800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFD1300802"],"award-info":[{"award-number":["2023YFD1300802"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32472954"],"award-info":[{"award-number":["32472954"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Abnormal placental angiogenesis contributes significantly to fetal growth restriction (FGR) and related complications. Methionine adenosyl\u2010transferase 2A (MAT2A) can regulate the process of embryonic development; however, the role of MAT2A in placental angiogenesis during fetal development remains poorly understood. In this study, placentas from paired normal birth weight (NBW) and FGR piglets were used to quantify placental vascular density and biochemical indexes, while porcine trophoblast cells (pTrs) and porcine\u00a0vascular endothelial cells (PVECs) were used to investigate the regulatory mechanism of MAT2A on placental angiogenesis. Here, we found that FGR placentas exhibited reduced vascular density and increased glycogen levels. Moreover, FGR placentas showed reduced\n                      <jats:italic>S<\/jats:italic>\n                      \u2010adenosylmethionine (SAM) levels and downregulated protein expression of MAT2A and CD31. Placental SAM levels were positively correlated with vascular density, while MAT2A expression was positively correlated with CD31 expression. Further study showed that MAT2A knockdown disrupted the metabolism of methionine, glycolysis, the tricarboxylic acid cycle and oxidative phosphorylation, and hindered protein synthesis, thereby impairing cell proliferation and migration in pTrs and\/or PVECs, and inhibited angiogenesis in a co\u2010culture system. In contrast, SAM supplementation promoted phosphorylation of ribosomal protein S6 kinase 1 (S6K1), downstream of the mammalian target of rapamycin complex 1 signalling pathway, and upregulated vascular endothelial growth factor\u2010A protein expression, thereby increasing endothelial cell tube formation. In conclusion, our study demonstrates the potential of MAT2A in interventional therapy for placental development of FGR.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70331-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            Placental vascular density is correlated with decreased\n                            <jats:italic>S<\/jats:italic>\n                            \u2010adenosylmethionine (SAM) levels caused by downregulated adenosyl\u2010transferase 2A (MAT2A) expression.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>MAT2A regulates the placental mTORC1 signalling pathway and protein synthesis.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>MAT2A knockdown disrupts methionine metabolism, glycolysis, the tricarboxylic acid cycle and oxidative phosphorylation.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>MAT2A regulates the proliferation and migration capacity of placental trophoblast and endothelial cells.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>MAT2A regulates placental angiogenesis via the SAM\u2013mTORC1\u2013S6K1\u2013VEGF\u2010A signalling pathway.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp290011","type":"journal-article","created":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T15:45:48Z","timestamp":1769269548000},"page":"2191-2211","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Methionine adenosyl\u2010transferase 2A promotes placental angiogenesis by regulating VEGF\u2010A translation via the mTORC1 signalling pathway"],"prefix":"10.1113","volume":"604","author":[{"given":"Rui","family":"Zhou","sequence":"first","affiliation":[{"name":"Animal Nutrition Institute Sichuan Agricultural University  Chengdu PR China"},{"name":"Key Laboratory of Animal Disease\u2010Resistant Nutrition of the 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