{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T20:09:13Z","timestamp":1785442153199,"version":"3.56.0"},"posted":{"date-parts":[[2025,12,31]]},"group-title":"Pharmacology and Toxicology","reference-count":53,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"crossref","award":["P30ES007033"],"award-info":[{"award-number":["P30ES007033"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"crossref","award":["T32ES007032"],"award-info":[{"award-number":["T32ES007032"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Washington Institute of Stem Cell and Regenerative Medicine Fellowship"},{"name":"University of Washington 3Rs Consortium"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Spermatogonial differentiation is controlled by distinct spatial and temporal activities of metabolizing enzymes and signaling molecule formation. In vitro models are reductionist ways to examine the interactions between Sertoli cells and spermatogonial stem cells, which may be therapeutic targets for infertility that cause non-obstructive azoospermia, due to either Sertoli-cell only syndrome, hypospermatogenesis or maturation arrest. Here, we find that nanomolar doses of isotretinoin are sufficient to drive\n                  <jats:italic>Stra8<\/jats:italic>\n                  expression in vitro, an interaction that is both dose-dependent and inhibitable. We compare complex in vitro models (CIVMs) seeded from cells isolated post-natal day 5 (PND 5) and post-natal day 10 (PND 10) Sprague Dawley rat testis. The CIVMs maintain metabolic capacity to produce bioactive retinoids form retinol. We also investigate the impact of common media supplementations on spermatogonial phenotype and find that they can impact the expression of\n                  <jats:italic>Stra8<\/jats:italic>\n                  and\n                  <jats:italic>Plzf<\/jats:italic>\n                  as markers of early differentiating and undifferentiated spermatogonia, respectively. These results highlight the power of\n                  <jats:italic>in vitro<\/jats:italic>\n                  models to investigate the dynamics of the spermatogonial niche.\n                <\/jats:p>","DOI":"10.64898\/2025.12.30.696417","type":"posted-content","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T09:50:13Z","timestamp":1767174613000},"source":"Crossref","is-referenced-by-count":1,"title":["Differential retinoic acid responses across testicular development\n                  <i>in vitro<\/i>"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1524-0878","authenticated-orcid":false,"given":"Brad C.","family":"Hansen","sequence":"first","affiliation":[{"name":"Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, U.S.A"},{"name":"Institute for Stem Cells and Regenerative Medicine, University of Washington, Seattle, Washington, U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A.","family":"Hatem","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, University of Washington, Seattle, Washington, U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas A.","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, University of Washington, Seattle, Washington, U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John K.","family":"Amory","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, Washington, U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine M.","family":"Faustman","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6534-9313","authenticated-orcid":false,"given":"Edward J.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, University of Washington, Seattle, Washington, U.S.A"},{"name":"Institute for Stem Cells and Regenerative Medicine, University of Washington, Seattle, Washington, U.S.A"},{"name":"Kidney Research Institute, University of Washington, Seattle, Washington, U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026010301350453000_2025.12.30.696417v1.1","unstructured":"Chandra A , Copen CE , Stephen EH . 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