{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:56:43Z","timestamp":1781672203417,"version":"3.54.5"},"reference-count":123,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Elevated circulating non-esterified fatty acids (NEFA), a hallmark of metabolic stress and negative energy balance, are increasingly associated with reduced female fertility. While most studies focus on late oocyte maturation, metabolic disturbances during follicular growth, particularly during the preantral \u2013 early antral transition, a critical window for establishing oocyte developmental competence may already impair oocyte quality. Here, we investigated whether sustained, physiologically buffered NEFA elevation during this stage affects oocyte developmental competence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Preantral follicles were cultured for 18\u202fdays in a three-dimensional ovine\n                      <jats:italic>in vitro<\/jats:italic>\n                      folliculogenesis system under physiological (70\u202f\u03bcM) or moderately elevated (140\u202f\u03bcM) NEFA conditions, with defined fatty acid composition and albumin buffering. The cytoprotective effects of the antioxidants Trolox and resveratrol were also evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Chronic exposure to moderately elevated NEFA induced a pro-oxidant follicular microenvironment, characterized by reactive oxygen species (ROS) accumulation and oxidative DNA damage, including increased 8-OHdG and mtDNA D-loop oxidation. This stress impaired cumulus cell function and somatic\u2013oocyte communication, reduced oocyte mtDNA copy number and mitochondrial activity, and compromised meiotic and developmental competence despite preserved follicular growth. Antioxidant treatment with Trolox restored mitochondrial function, normalized cumulus activity, and rescued blastocyst development, partially reversing the NEFA-induced phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Prolonged moderate NEFA elevation during early folliculogenesis impairs oocyte competence despite preserved follicular morphology, identifying chronic lipotoxicity and redox imbalance as early and clinically relevant determinants of impaired fertility.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1840637","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:42:43Z","timestamp":1781671363000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Moderate NEFA reprogram early follicular development and oocyte competence: evidence for a targetable redox mechanism"],"prefix":"10.3389","volume":"13","author":[{"given":"Camila","family":"Rojo-Fleming","sequence":"first","affiliation":[{"name":"Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo","place":["Teramo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Di Berardino","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo","place":["Teramo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Peserico","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo","place":["Teramo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Canciello","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo","place":["Teramo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Camerano Spelta Rapini","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo","place":["Teramo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianna","family":"Sacchetti","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo","place":["Teramo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Capacchietti","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo","place":["Teramo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"D\u2019Antonio","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo","place":["Teramo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donato","family":"Angelino","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo","place":["Teramo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Serafini","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo","place":["Teramo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebasti\u00e1n","family":"C\u00e1novas","sequence":"additional","affiliation":[{"name":"Department of Physiology, International Excellence Campus for Higher Education and Research (Campus Mare Nostrum), University of Murcia","place":["Murcia, Spain"]},{"name":"Biomedical Research Institute of Murcia Pascual Parrilla-IMIB","place":["Murcia, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Barboni","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo","place":["Teramo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.tem.2025.07.004","article-title":"Triglyceride-based lipotoxicity in the pathophysiology of chronic diseases","volume":"37","author":"Liu","year":"2025","journal-title":"Trends Endocrinol 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