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Mol. Biosci."],"abstract":"<jats:p>Embryonic developmental delay constitutes a key pathological feature in implantation failure and the early loss of pregnancy in human assisted reproductive technology (ART). This condition is mechanistically linked to mitochondrial dysfunction and epigenetic reprogramming defects during maternal-embryonic communication. Here, we established a mouse model of fetal bovine serum (FBS)-induced embryonic developmental delay and performed comprehensive proteomic profiling with data-independent acquisition (DIA) quantitative proteomics. In addition, we also used immunofluorescence, reactive oxygen species (ROS) determination, and protein inhibitors to determine the specific role of FABP4, a fatty acid transport protein, in the early stages of embryo development. Our analysis identified 165 differentially expressed proteins (DEPs); of these, 103 were significantly downregulated (P &amp;lt; 0.05; fold change &amp;gt;1.5) and 62 were upregulated (P &amp;lt; 0.05; fold change &amp;lt;0.66). Gene ontology and KEGG pathway analyses revealed significant enrichment of DEPs in lipid metabolic reprogramming (particularly arginine-proline metabolism), cytoskeletal organisation, and the negative regulation of RNA splicing. Integrated multi-omics analysis revealed a tripartite regulatory mechanism: (1) cytoskeletal destabilisation, as evidenced by the downregulation of 19\/24 cytoskeletal organisation proteins (P &amp;lt; 0.01; false discovery rate [FDR]: 0.089); (2) disrupted nucleocytoplasmic transport and splicing, characterised by the reduced expression of 5\/7 ribosomal shuttle proteins and impaired nucleoporin (Kpna2\/Kpnb1) functionality; and (3) metabolic dysregulation, resulting in the complete downregulation of all six KEGG-enriched metabolic proteins and PF00061 domain proteins (P &amp;lt; 0.01; FDR: 0.004), including three fatty acid transporters and two fatty acid-binding proteins, indicating compromised ATP synthesis and lipid metabolism. At a concentration of 200 nm, the FABP4 inhibitor BMS-309403 can cause embryonic retardation and increase the levels of ROS. Collectively, our findings demonstrate that the fatty acid transporter FABP4 is expressed in the early 8-cell embryos of mice. We provide new insights into the mechanisms underlying embryonic development delay caused by FBS. Furthermore, proteomic analysis revealed that FABP4 is regulated by an integrated cytoskeleton-nuclear-cytoplasmic transport-metabolic network. The inhibition of FABP4 led to the retardation of embryonic development and increased the levels of ROS.<\/jats:p>","DOI":"10.3389\/fmolb.2026.1781512","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T04:23:04Z","timestamp":1783398184000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular mechanisms underlying fetal bovine serum-induced developmental delay in mouse embryos: a data-independent acquisition (DIA)-based proteomics study"],"prefix":"10.3389","volume":"13","author":[{"given":"Songjie","family":"Lv","sequence":"first","affiliation":[{"name":"Department of Assisted Reproduction, Urumqi Maternal and Child Health Hospital","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Ying","sequence":"additional","affiliation":[{"name":"Biotechnology Research Institute, Xinjiang Academy of Animal Sciences","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bian","family":"Lou","sequence":"additional","affiliation":[{"name":"Department of Assisted Reproduction, Urumqi Maternal and Child Health Hospital","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luhan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Scientific Research Department, Urumqi Maternal and Child Health Hospital","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayan","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Assisted Reproduction, Urumqi Maternal and Child Health Hospital","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Assisted Reproduction, Urumqi Maternal and Child Health Hospital","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Assisted Reproduction, Urumqi Maternal and Child Health Hospital","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.gene.2018.07.035","article-title":"Diverse roles of fatty acid binding proteins (FABPs) in development and pathogenesis of cancers","volume":"676","author":"Amiri","year":"2018","journal-title":"Gene"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e08851","DOI":"10.7554\/eLife.08851","article-title":"Maternal LSD1\/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation","volume":"5","author":"Ancelin","year":"2016","journal-title":"Elife"},{"key":"B3","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.jevs.2018.05.078","article-title":"Early embryo development in mares: proteomics of uterine fluid","volume":"66","author":"Bastos","year":"2018","journal-title":"J. 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