{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T06:12:38Z","timestamp":1775023958428,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T00:00:00Z","timestamp":1774742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Comitato Telethon Fondazione Onlus","doi-asserted-by":"publisher","award":["GP0049Y01"],"award-info":[{"award-number":["GP0049Y01"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sardinian Autonomous Region","award":["cRP3-154"],"award-info":[{"award-number":["cRP3-154"]}]},{"name":"CNR","award":["DG.RSTL.060.001"],"award-info":[{"award-number":["DG.RSTL.060.001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Ovarian reserve and reproductive life are closely linked concepts in female reproductive biology. The ovarian reserve consists of primordial follicles and refers to the number and quality of oocytes (eggs) remaining in the ovaries at any given time. Follicular dynamics shape a woman\u2019s reproductive lifespan, ultimately leading to menopause. Elucidating the underlying genetic and molecular pathways of follicle maturation and depletion is thus crucial for understanding menopausal onset and progression, both in normal and pathophysiological contexts, such as primary ovarian insufficiency, defined as menopause before the age of 40. A key factor in ovarian differentiation and fertility maintenance is FOXL2, a forkhead family transcription factor that plays a crucial role in follicle formation and development, ovarian maintenance, and sex determination. By employing a ChIP-Seq approach in mice, we identified a previously unreported binding of FOXL2 to a Tsc1 regulatory region. Our data, along with a thorough literature review, support the hypothesis that FOXL2-mediated activation of Tsc1 in granulosa cells can help maintain primordial follicles in a dormant state by suppressing mTORC1 signalling. Understanding the mechanisms behind ovarian reserve may lay the foundation for developing novel fertility preservation strategies, improving fertility treatment protocols and promoting in vitro activation of cryopreserved ovarian tissue to support folliculogenesis.<\/jats:p>","DOI":"10.3390\/biom16040510","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T13:40:52Z","timestamp":1774878052000},"page":"510","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evidence for FOXL2 Association with the Tsc1 Regulatory Region in Mice"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7321-2384","authenticated-orcid":false,"given":"Mara","family":"Marongiu","sequence":"first","affiliation":[{"name":"Institute for Genetic and Biomedical Research, National Research Council, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loredana","family":"Marcia","sequence":"additional","affiliation":[{"name":"Institute for Genetic and Biomedical Research, National Research Council, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Sbardellati","sequence":"additional","affiliation":[{"name":"Centre for Advanced Studies, Research and Development in Sardinia (CRS4), Science and Technology Park Polaris, 09050 Pula, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6757-373X","authenticated-orcid":false,"given":"Manila","family":"Deiana","sequence":"additional","affiliation":[{"name":"Institute for Genetic and Biomedical Research, National Research Council, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isadora","family":"Asunis","sequence":"additional","affiliation":[{"name":"Institute for Genetic and Biomedical Research, National Research Council, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1890-9821","authenticated-orcid":false,"given":"Emanuele","family":"Pelosi","sequence":"additional","affiliation":[{"name":"National Institute on Aging, National Institute of Health, DHHS, Baltimore, MD 21224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Coschiera","sequence":"additional","affiliation":[{"name":"National Institute on Aging, National Institute of Health, DHHS, Baltimore, MD 21224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Crobu","sequence":"additional","affiliation":[{"name":"Institute for Genetic and Biomedical Research, National Research Council, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Loi","sequence":"additional","affiliation":[{"name":"Institute for Genetic and Biomedical Research, National Research Council, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilio","family":"Melis","sequence":"additional","affiliation":[{"name":"Institute for Genetic and Biomedical Research, National Research Council, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Cristina","family":"Mostallino","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, National Research Council, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Meloni","sequence":"additional","affiliation":[{"name":"Institute for Genetic and Biomedical Research, National Research Council, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Cusano","sequence":"additional","affiliation":[{"name":"Centre for Advanced Studies, Research and Development in Sardinia (CRS4), Science and Technology Park Polaris, 09050 Pula, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Cucca","sequence":"additional","affiliation":[{"name":"Institute for Genetic and Biomedical Research, National Research Council, 09042 Monserrato, Italy"},{"name":"Department of Biomedical Science, University of Sassari, 07100 Sassari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Uda","sequence":"additional","affiliation":[{"name":"Institute for Genetic and Biomedical Research, National Research Council, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9128-8537","authenticated-orcid":false,"given":"Laura","family":"Crisponi","sequence":"additional","affiliation":[{"name":"Institute for Genetic and Biomedical Research, National Research Council, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1262\/jrd.2021-040","article-title":"Regulation of primordial follicle formation, dormancy, and activation in mice","volume":"67","author":"Nagamatsu","year":"2021","journal-title":"J. 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