{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T04:30:50Z","timestamp":1786595450456,"version":"build-2736575974"},"reference-count":25,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"China National Natural Science Foundation","doi-asserted-by":"crossref","award":["32573220"],"award-info":[{"award-number":["32573220"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"China National Natural Science Foundation","doi-asserted-by":"crossref","award":["32072738"],"award-info":[{"award-number":["32072738"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"China National Natural Science Foundation","doi-asserted-by":"crossref","award":["31902160"],"award-info":[{"award-number":["31902160"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["32573220"],"award-info":[{"award-number":["32573220"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["32072738"],"award-info":[{"award-number":["32072738"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["31902160"],"award-info":[{"award-number":["31902160"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"crossref","award":["ZR2025MS443"],"award-info":[{"award-number":["ZR2025MS443"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"crossref","award":["ZR2022MC036"],"award-info":[{"award-number":["ZR2022MC036"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Zearalenone (ZEN) exposure poses health risks to both humans and animals. Although evidence indicates that ZEN significantly impairs oocyte developmental competence, the underlying mechanisms remain largely unclear. While it is recognized that prepubertal animals are particularly vulnerable to ZEN and that juvenile in vitro embryo transfer represents a promising strategy for accelerating genetic progress, the potential impact of ZEN on developmental competence of prepubertal oocytes remains uninvestigated. Methods: In vivo, we administered graded oral doses of ZEN to female mice at prepubertal (3 weeks), peripubertal (6 weeks), and post-pubertal (8 weeks) stages and assessed oocyte developmental potential and related markers and ZEN residues in ovaries and livers following superovulation. In vitro, oocytes isolated from mice of each age group were subjected to graded ZEN concentrations during in vitro maturation, followed by evaluation of oocyte developmental potential. Results: This study shows that oral ZEN exposure impairs oocyte developmental competence and cumulus expansion, and disrupts oocyte redox homeostasis, mitochondrial integrity and glutathione biosynthesis in a mouse age-specific manner, with prepubertal (3-week-old) mice exhibiting the greatest susceptibility. Assessment of systemic ZEN disposition shows that ZEN concentrations in both ovarian and hepatic tissues were significantly higher in 3-week-old mice than in 6- and 8-week-old mice. Furthermore, exposure of oocytes to graded ZEN concentrations during in vitro maturation demonstrate that oocytes from prepubertal mice exhibit intrinsically heightened susceptibility to ZEN-induced functional deficits relative to those from sexually mature adults. Conclusions: This study demonstrates that ZEN exposure compromises oocyte developmental competence in a host age-dependent manner, and the heightened vulnerability in prepubertal oocytes is associated with both increased ovarian ZEN bioavailability and their intrinsically greater sensitivity to ZEN.<\/jats:p>","DOI":"10.3390\/cells15161444","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T10:32:16Z","timestamp":1786444336000},"page":"1444","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Animal Age-Dependent Susceptibility of Mouse Oocytes to Zearalenone-Induced Developmental Impairment: Roles of Pharmacokinetic Exposure and Intrinsic Oocyte Sensitivity"],"prefix":"10.3390","volume":"15","author":[{"given":"Si-Tong","family":"Liu","sequence":"first","affiliation":[{"name":"Shandong Provincial Key Laboratory for Livestock Germplasm Innovation & Utilization, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Gui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory for Livestock Germplasm Innovation & Utilization, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Li","family":"Xu","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory for Livestock Germplasm Innovation & Utilization, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0919-5882","authenticated-orcid":false,"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory for Livestock Germplasm Innovation & Utilization, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Gong","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory for Livestock Germplasm Innovation & Utilization, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Jie","family":"Yuan","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory for Livestock Germplasm Innovation & Utilization, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6437-6259","authenticated-orcid":false,"given":"Jing-He","family":"Tan","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory for Livestock Germplasm Innovation & Utilization, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0460-8358","authenticated-orcid":false,"given":"Ming-Jiu","family":"Luo","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory for Livestock Germplasm Innovation & Utilization, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7034","DOI":"10.1021\/acs.jafc.6b04847","article-title":"Worldwide Occurrence of Mycotoxins in Cereals and Cereal-Derived Food Products: Public Health Perspectives of Their Co-Occurrence","volume":"65","author":"Lee","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1095\/biolreprod.107.062711","article-title":"Exposure of Oocytes to the Fusarium Toxins Zearalenone and Deoxynivalenol Causes Aneuploidy and Abnormal Embryo Development in Pigs","volume":"77","author":"Malekinejad","year":"2007","journal-title":"Biol. Reprod."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1002\/em.21833","article-title":"Oocyte Quality in Mice Is Affected by a Mycotoxin-Contaminated Diet","volume":"55","author":"Hou","year":"2014","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1071\/RD20273","article-title":"Invivo Zearalenone Exposure Dose-Dependently Compromises Mouse Oocyte Competence by Impairing Chromatin Configuration and Gene Transcription","volume":"33","author":"Pan","year":"2021","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_5","unstructured":"UNEP\/UNICEF\/WHO (2002). Children in the New Millennium: Environmental Impact on Health, UNEP\/Earthprint. Available online: https:\/\/iris.who.int\/handle\/10665\/42506."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"EFSA (2016). Appropriateness to Set a Group Health-Based Guidance Value for Zearalenone and Its Modified Forms. EFSA J., 14, e04425.","DOI":"10.2903\/j.efsa.2016.4425"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"EFSA (2011). Scientific Opinion on the Risks for Public Health Related to the Presence of Zearalenone in Food. EFSA J., 9, 2197.","DOI":"10.2903\/j.efsa.2011.2197"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7757","DOI":"10.1021\/acs.jafc.0c01943","article-title":"Toxicokinetic Studies in Piglets Reveal Age-Related Differences in Systemic Exposure to Zearalenone, Zearalenone-14-Glucoside, and Zearalenone-14-Sulfate","volume":"68","author":"Catteuw","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Gordon, I. (2017). Controlling Onset of Puberty. Reproductive Technologies in Farm Animals, CABI.","DOI":"10.1079\/9781780646022.0000"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"171","DOI":"10.2527\/1990.681171x","article-title":"Effect of Prepubertal Consumption of Zearalenone on Puberty and Subsequent Reproduction of Gilts","volume":"68","author":"Green","year":"1990","journal-title":"J. Anim. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"RD25155","DOI":"10.1071\/RD25155","article-title":"Exploring the Potential of Prepubertal Oocytes: A Small Ruminant Model","volume":"38","author":"Paramio","year":"2026","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.taap.2017.05.024","article-title":"The Impact of Zearalenone on The Meiotic Progression and Primordial Follicle Assembly During Early Oogenesis","volume":"329","author":"Liu","year":"2017","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.taap.2015.09.010","article-title":"The Influence of N-Acetyl-L-Cysteine on Damage of Porcine Oocyte Exposed to Zearalenone in Vitro","volume":"289","author":"Lai","year":"2015","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.theriogenology.2021.10.008","article-title":"Zearalenone Exposure Impairs Organelle Function During Porcine Oocyte Meiotic Maturation","volume":"177","author":"Wang","year":"2022","journal-title":"Theriogenology"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Li, Z., Liu, Y., Ma, T., Lv, C., Li, Y., Duan, H., Zhao, X., Wang, J., and Zhang, Y. (2023). Smart-Seq2 Technology Reveals a Novel Mechanism That Zearalenone Inhibits the in Vitro Maturation of Ovine Oocytes by Influencing Tnfaip6 Expression. Toxins, 15.","DOI":"10.3390\/toxins15100617"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e240128","DOI":"10.1530\/REP-24-0128","article-title":"Expression Profiling and Function Analysis Identified New Genes Regulating Cumulus Expansion and Cumulus Cell Apoptosis in Mouse Oocytes","volume":"168","author":"Zhang","year":"2024","journal-title":"Reproduction"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1095\/biolreprod.112.103887","article-title":"Developmental Arrest and Mouse Antral Not-Surrounded Nucleolus Oocytes","volume":"88","author":"Monti","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/ng1079","article-title":"Zygote Arrest 1 (Zar1) is a Novel Maternal-Effect Gene Critical for the Oocyte-to-Embryo Transition","volume":"33","author":"Wu","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e13231","DOI":"10.1111\/cpr.13231","article-title":"Maternal Prkce Expression in Mature Oocytes Is Critical for the First Cleavage Facilitating Maternal-to-Zygotic Transition in Mouse Early Embryos","volume":"55","author":"Zhang","year":"2022","journal-title":"Cell Prolif."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.fct.2019.02.031","article-title":"Effects of Zearalenone and Its Derivatives on The Synthesis and Secretion of Mammalian Sex Steroid Hormones: A Review","volume":"126","author":"Zheng","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Alyoshina, N.M., Beketova, M.V., Tkachenko, M.D., Nikishina, Y.O., Frolova, V.S., Malchenko, L.A., Semenova, M., Rubtsova, M., and Nikishin, D.A. (2025). Fluoxetine Disrupts Ovarian Serotonin Signaling and Oocyte Competence in Mice. Pharmaceuticals, 18.","DOI":"10.3390\/ph18111647"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Gaj\u0119cka, M., Zielonka, \u0141., Babuchowski, A., and Gaj\u0119cki, M.T. (2022). Exposure to Low Zearalenone Doses and Changes in the Homeostasis and Concentrations of Endogenous Hormones in Selected Steroid-Sensitive Tissues in Pre-Pubertal Gilts. Toxins, 14.","DOI":"10.3390\/toxins14110790"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zielonka, \u0141., Gaj\u0119cka, M., Lisieska-\u017bo\u0142nierczyk, S., D\u0105browski, M., and Gaj\u0119cki, M.T. (2020). The Effect of Different Doses of Zearalenone in Feed on the Bioavailability of Zearalenone and Alpha-Zearalenol, and the Concentrations of Estradiol and Testosterone in the Peripheral Blood of Pre-Pubertal Gilts. Toxins, 12.","DOI":"10.3390\/toxins12030144"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Jiao, G.Z., Cao, X.Y., Cui, W., Lian, H.Y., Miao, Y.L., Wu, X.F., Han, D., and Tan, J.H. (2013). Developmental Potential of Prepubertal Mouse Oocytes Is Compromised Due Mainly to Their Impaired Synthesis of Glutathione. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058018"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s40104-025-01213-w","article-title":"Contamination of Aflatoxin B1, Deoxynivalenol and Zearalenone in Feeds in China from 2021 to 2024","volume":"16","author":"Liu","year":"2025","journal-title":"J. Anim. Sci. Biotechnol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/16\/1444\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T04:25:53Z","timestamp":1786595153000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/16\/1444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,11]]},"references-count":25,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cells15161444"],"URL":"https:\/\/doi.org\/10.3390\/cells15161444","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,11]]}}}