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Despite extensive research on the cellular functions of Brefeldin A (BFA) as an intracellular transport inhibitor, its specific effects and mechanisms on ovarian development\/aging remain inadequately understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mice and porcine oocytes\/granulosa cells (GCs) were treated with BFA. Morphological and omics analyses (including Western blot, real\u2010time polymerase chain reaction (RT\u2010PCR), transcriptomics, and metabolomics) were conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In 3\u2010week\u2010old female mice, BFA treatment significantly suppressed oocyte maturation, induced apoptosis, and increased estradiol and LH levels. This treatment upregulated apoptosis\u2010related genes while downregulating proliferation\u2010associated genes. Additionally, BFA elevated senescence markers (p21 and p26) and decreased the activity of the longevity gene SIRT6. In porcine oocytes, BFA reduced the maturation rate and lowered mRNA levels of key maturation\u2010related genes, LHX8 and GDF9. In porcine GCs, BFA increased apoptosis and upregulated genes such as Caspase\u20103, BAX, and P21, while downregulating genes associated with proliferation and longevity. Similar effects were observed in 12\u2010month\u2010old female mice, indicating consistency across age groups. Metabolomic analysis in these mice revealed that BFA primarily impacted pathways related to steroid biosynthesis, ovarian steroidogenesis, and estrogen signaling. Transcriptomic analysis in 12\u2010month\u2010old female mice further demonstrated that BFA disrupted ovarian function through multiple mechanisms, including modulation of the GnRH signaling pathway, activation of the FOXO pathway, and interference with meiosis\u2010related gene expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings are pivotal for advancing the understanding of ovarian aging, dysfunctions, and diseases, and ultimately facilitate addressing BFA's potential adverse effects on reproductive health\/aging.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70102","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T10:25:02Z","timestamp":1762856702000},"page":"2053-2068","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Disruption 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