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Our population\u2010based study showed elevated ferroptosis levels in all\u2010cause FGR placentae. Environmental stressor cadmium (Cd) was used to generate an FGR mouse model, which exhibited elevated placental ferroptosis. Ferroptosis inhibitor ferrostatin\u20101 reversed environmental Cd\u2010induced FGR. Targeted oxidized lipidomics identified the peroxisome as a target organelle for prenatal Cd\u2010induced placental ferroptosis. Furthermore, Cd induced excessive activation of PEX5\u2010dependent pexophagy in placentae. By establishing a placental\n                    <jats:italic>Pex5<\/jats:italic>\n                    \u2010knockdown mouse, pexophagy was confirmed to drive environmental Cd\u2010induced placental ferroptosis. Mechanistically, pexophagy drives the degradation of the H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u2010scavenging enzyme and the fatty\u2010acid \u03b2\u2010oxidation enzymes, thereby causing lipid peroxidation and placental ferroptosis. Notably, environmental Cd upregulated PEX2, an E3 ligase mediating PEX5 monoubiquitination, thereby driving pexophagy and placental ferroptosis. Furthermore, METTL14\u2010mediated m6A modification enhanced the stability of placental\n                    <jats:italic>PEX2<\/jats:italic>\n                    mRNA in an ELAVL1\u2010dependent manner under environmental Cd. SAH, a METTL14 inhibitor, alleviated Cd\u2010induced placental pexophagy, ferroptosis, and FGR. High\u2010temperature also decreased GPX4 and increased PEX2, PEX5, and METTL14 in placentae. Overall, our findings uncover a novel m6A\u2010PEX2\u2010PEX5 axis driving pexophagy\u2010dependent placental ferroptosis, offering placental pexophagy as a therapeutic target for FGR and fetal\u2010origin adult diseases.\n                  <\/jats:p>","DOI":"10.1002\/advs.77068","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T15:44:13Z","timestamp":1786549453000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["m6A\u2010Driven Pexophagy Triggers Placental Ferroptosis to Impair Fetal Growth Upon Environmental Stress"],"prefix":"10.1002","author":[{"given":"Xin\u2010Xin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Toxicology School of Public Health Anhui Medical University  Hefei China"},{"name":"Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes  Hefei 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