{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:20:00Z","timestamp":1789046400805,"version":"build-2803163510"},"posted":{"date-parts":[[2024,6,25]]},"group-title":"Developmental Biology","reference-count":98,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,6,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The female reproductive system is one of the first to age in humans, resulting in infertility and endocrine disruptions. The aging ovary assumes a fibro-inflammatory milieu which negatively impacts gamete quantity and quality as well as ovulation. Here we tested whether the systemic delivery of anti-inflammatory (Etanercept) or anti-fibrotic (Pirfenidone) drugs attenuates ovarian aging in mice. We first evaluated the ability of these drugs to decrease the expression of fibro-inflammatory genes in primary ovarian stromal cells. Whereas Etanercept did not block\n                  <jats:italic>Tnf<\/jats:italic>\n                  expression in ovarian stromal cells, Pirfenidone significantly reduced\n                  <jats:italic>Col1a1<\/jats:italic>\n                  expression. We then tested Pirfenidone\n                  <jats:italic>in vivo<\/jats:italic>\n                  where the drug was delivered systemically via mini-osmotic pumps for 6-weeks. Pirfenidone mitigated the age-dependent increase in ovarian fibrosis without impacting overall health parameters. Ovarian function was improved in Pirfenidone-treated mice as evidenced by increased follicle and corpora lutea number, AMH levels, and improved estrous cyclicity. Transcriptomic analysis revealed that Pirfenidone treatment resulted in an upregulation of reproductive function-related genes at 8.5 months and a downregulation of inflammatory genes at 12 months of age. These findings demonstrate that reducing the fibroinflammatory ovarian microenvironment improves ovarian function, thereby supporting modulating the ovarian environment as a therapeutic avenue to extend reproductive longevity.\n                <\/jats:p>","DOI":"10.1101\/2024.06.21.600035","type":"posted-content","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T21:25:14Z","timestamp":1719350714000},"source":"Crossref","is-referenced-by-count":5,"title":["Systemic low-dose anti-fibrotic treatment attenuates ovarian aging in the mouse"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8273-1434","authenticated-orcid":false,"given":"Farners","family":"Amargant","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Vieira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0095-0685","authenticated-orcid":false,"given":"Michele T.","family":"Pritchard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3756-9394","authenticated-orcid":false,"given":"Francesca E.","family":"Duncan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"4","key":"2024062615201103000_2024.06.21.600035v1.1","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1093\/biolre\/ioab115","article-title":"Germ cells of the mammalian female: A limited or renewable resource?dagger","volume":"105","year":"2021","journal-title":"Biol Reprod"},{"key":"2024062615201103000_2024.06.21.600035v1.2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2014-1020"},{"key":"2024062615201103000_2024.06.21.600035v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2021.11.005"},{"key":"2024062615201103000_2024.06.21.600035v1.4","doi-asserted-by":"publisher","DOI":"10.1210\/er.2009-0006"},{"key":"2024062615201103000_2024.06.21.600035v1.5","doi-asserted-by":"crossref","first-page":"952471","DOI":"10.3389\/fendo.2022.952471","article-title":"Aging conundrum: A perspective for ovarian aging","volume":"13","year":"2022","journal-title":"Front Endocrinol (Lausanne"},{"key":"2024062615201103000_2024.06.21.600035v1.6","doi-asserted-by":"crossref","unstructured":"Hagg, S. and J. Jylhava , Sex differences in biological aging with a focus on human studies. Elife, 2021. 10.","DOI":"10.7554\/eLife.63425"},{"issue":"6","key":"2024062615201103000_2024.06.21.600035v1.7","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S2213-8587(22)00142-5","article-title":"Menopause: a turning point for women\u2019s health","volume":"10","author":"The Lancet Diabetes, E.","year":"2022","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2024062615201103000_2024.06.21.600035v1.8","doi-asserted-by":"crossref","unstructured":"Francesca E. 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