{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:53:35Z","timestamp":1790034815444,"version":"4.0.1"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T00:00:00Z","timestamp":1723507200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mouse spermatogenesis entails the maintenance and self-renewal of spermatogonial stem cells (SSCs), which require a complex web-like signaling network transduced by various cytokines. Although brain-derived neurotrophic factor (BDNF) is expressed in Sertoli cells in the testis, and its receptor tropomyosin receptor kinase B (TrkB) is expressed in the spermatogonial population containing SSCs, potential functions of BDNF for spermatogenesis have not been uncovered. Here, we generate BDNF conditional knockout mice and find that BDNF is dispensable for\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    spermatogenesis and fertility. However,\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    , we reveal that\n                    <jats:italic toggle=\"yes\">BDNF<\/jats:italic>\n                    -deficient germline stem cells (GSCs) exhibit growth potential not only in the absence of glial cell line-derived neurotrophic factor (GDNF), a master regulator for GSC proliferation, but also in the absence of other factors, including epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and insulin. GSCs grown without these factors are prone to differentiation, yet they maintain expression of promyelocytic leukemia zinc finger (\n                    <jats:italic toggle=\"yes\">Plzf<\/jats:italic>\n                    ), an undifferentiated spermatogonial marker. Inhibition of phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK)\/extracellular signal-regulated kinase (ERK), and Src pathways all interfere with the growth of BDNF-deficient GSCs. Thus, our findings suggest a role for BDNF in maintaining the undifferentiated state of spermatogonia, particularly in situations where there is a shortage of growth factors.\n                  <\/jats:p>","DOI":"10.4103\/aja202457","type":"journal-article","created":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T03:16:05Z","timestamp":1723518965000},"page":"37-43","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":3,"title":["A behind-the-scenes role of BDNF in the survival and differentiation of spermatogonia"],"prefix":"10.4103","volume":"27","author":[{"given":"Shin-ichi","family":"Tomizawa","sequence":"first","affiliation":[{"name":"Department of Histology and Cell Biology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazushige","family":"Kuroha","sequence":"additional","affiliation":[{"name":"Department of Histology and Cell Biology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michio","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Histology and Cell Biology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuniko","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Histology and Cell Biology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Ohbo","sequence":"additional","affiliation":[{"name":"Department of Histology and Cell Biology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,8,13]]},"reference":[{"key":"R1-20250304","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1146\/annurev-cellbio-101512-122353","article-title":"Spermatogonial stem cell self-renewal and development","volume":"29","author":"Kanatsu-Shinohara","year":"2013","journal-title":"Annu Rev Cell Dev Biol"},{"key":"R3-20250304","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.semcdb.2014.01.003","article-title":"Microtubules and spermatogenesis","volume":"30","author":"O'Donnell","year":"2014","journal-title":"Semin Cell Dev Biol"},{"key":"R4-20250304","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1095\/biolreprod.103.017012","article-title":"Long-term proliferation in culture and germline transmission of mouse male germline stem cells","volume":"69","author":"Kanatsu-Shinohara","year":"2003","journal-title":"Biol 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factors essential for self-renewal and expansion of mouse spermatogonial stem cells","volume":"101","author":"Kubota","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R9-20250304","doi-asserted-by":"crossref","first-page":"3855","DOI":"10.1242\/jcs.00786","article-title":"Novel functions and signalling pathways for GDNF","volume":"116","author":"Sariola","year":"2003","journal-title":"J Cell Sci"},{"key":"R10-20250304","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1126\/science.287.5457.1489","article-title":"Regulation of cell fate decision of undifferentiated spermatogonia by GDNF","volume":"287","author":"Meng","year":"2000","journal-title":"Science"},{"key":"R11-20250304","doi-asserted-by":"crossref","first-page":"4155","DOI":"10.1242\/dev.02004","article-title":"Genetic and epigenetic properties of mouse male germline stem cells during long-term 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Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/aja202457","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T19:27:05Z","timestamp":1786735625000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/aja202457"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,13]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.4103\/aja202457","relation":{},"ISSN":["1745-7262","1008-682X"],"issn-type":[{"value":"1745-7262","type":"print"},{"value":"1008-682X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,13]]},"assertion":[{"value":"2023-10-31","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-17","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}