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However, the molecular mechanisms underpinning oocyte developmental potential during bovine antral follicle growth are still unclear. Here, we used a modified single-cell multi-omics approach to analyze the transcriptome, DNA methylome, and chromatin accessibility in parallel for oocytes and cumulus cells collected from bovine antral follicles of different sizes. Transcriptome profiling identified three types of oocytes (small, medium, and large) that underwent different developmental trajectories, with large oocytes exhibiting the largest average follicle size and characteristics resembling metaphase-II oocytes. Differential expression analysis and real-time polymerase chain reaction assay showed that most replication-dependent histone genes were highly expressed in large oocytes. The joint analysis of multi-omics data revealed that the transcription of 20 differentially expressed genes in large oocytes was associated with both DNA methylation and chromatin accessibility. In addition, oocyte\u2013cumulus interaction analysis showed that inflammation, DNA damage, and p53 signaling pathways were active in small oocytes, which had the smallest average follicle sizes. We further confirmed that p53 pathway inhibition in the in vitro maturation experiments using oocytes obtained from small antral follicles could improve the quality of oocytes and increased the blastocyte rate after in vitro fertilization and culture. Our work provides new insights into the intricate orchestration of bovine oocyte fate determination during antral folliculogenesis, which is instrumental for optimizing in vitro maturation techniques to optimize oocyte quality.<\/jats:p>","DOI":"10.1093\/biolre\/ioae114","type":"journal-article","created":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T00:57:58Z","timestamp":1722041878000},"page":"815-833","source":"Crossref","is-referenced-by-count":9,"title":["Decoding molecular features of bovine oocyte fate during antral follicle growth via single-cell multi-omics analysis"],"prefix":"10.1093","volume":"111","author":[{"given":"Qiang","family":"Zhang","sequence":"first","affiliation":[{"name":"Shihezi University College of Animal Science and Technology, , Shihezi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyao","family":"Zhang","sequence":"additional","affiliation":[{"name":"China Agricultural University State Key Laboratory of Animal Biotech Breeding, Frontiers Science Center for Molecular Design Breeding (MOE), College of Animal Science and Technology, , Beijing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Chang","sequence":"additional","affiliation":[{"name":"Shenzhen University Medical School Department of Biochemistry and Molecular Biology, , Shenzhen,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Tongji University Translational Medical Center for Stem Cell Therapy & Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujun","family":"Yao","sequence":"additional","affiliation":[{"name":"China Agricultural University State Key Laboratory of Animal Biotech Breeding, Frontiers Science Center for Molecular Design Breeding (MOE), College of Animal Science and Technology, , Beijing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Liu","sequence":"additional","affiliation":[{"name":"China Agricultural University State Key Laboratory of Animal Biotech Breeding, Frontiers Science Center for Molecular Design Breeding (MOE), College of Animal Science and Technology, , Beijing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihuan","family":"Du","sequence":"additional","affiliation":[{"name":"China Agricultural University State Key Laboratory of Animal Biotech Breeding, Frontiers Science Center for Molecular Design Breeding (MOE), College of Animal Science and Technology, , Beijing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Wang","sequence":"additional","affiliation":[{"name":"Shihezi University College of Animal Science and Technology, , Shihezi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingrong","family":"Guo","sequence":"additional","affiliation":[{"name":"Hubei University of Medicine Hubei Key Laboratory of Embryonic Stem Cell Research Hubei Clinical Research Center for Umbilical Cord Blood Hematopoietic Stem Cells Taihe Hospital, , Shiyan,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongsheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shihezi University College of Animal Science and Technology, , Shihezi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weibin","family":"Zeng","sequence":"additional","affiliation":[{"name":"Shihezi University College of Animal Science and Technology, , Shihezi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Gao","sequence":"additional","affiliation":[{"name":"China Agricultural University State Key Laboratory of Animal Biotech Breeding, Frontiers Science Center for Molecular Design Breeding (MOE), College of Animal Science and Technology, , Beijing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,7,26]]},"reference":[{"key":"2024101506320997600_ref1","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.1152\/physrev.00032.2022","article-title":"Making a good egg: human oocyte health, aging, and in vitro development","volume":"103","author":"Telfer","year":"2023","journal-title":"Physiol Rev"},{"key":"2024101506320997600_ref2","doi-asserted-by":"crossref","first-page":"8","DOI":"10.7554\/eLife.43738","article-title":"Amplification of a broad transcriptional program 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