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It has been demonstrated that the omega\u20103 polyunsaturated fatty acids (PUFAs) benefits mature spermatozoa. However, whether omega\u20103 can protect endogenous spermatogonia and the detailed mechanisms are still unclear. Evaluate of spermatogenesis function (in vivo) were examined by histopathological analysis, immunofluorescence staining, and western blotting. The levels of lipid metabolites in testicular tissue were determined via liquid chromatography. We investigated the effect of lipid metabolites on Sertoli cells provided paracrine factors to regulate spermatogonia proliferation and differentiation using co\u2010culture system. In our study, we showed that omega\u20103 PUFAs significantly improved the process of sperm production and elevated the quantity of both undifferentiated Lin28+ spermatogonia and differentiated c\u2010kit+ spermatogonia in a mouse model where spermatogenic function was disrupted by busulfan. Mass spectrometry revealed an increase in the levels of several omega\u20103 metabolites in the testes of mice fed with omega\u20103 PUFAs. The eicosapentaenoic acid metabolite 12\u2010hydroxyeicosapentaenoic acid (12\u2010HEPE) up\u2010regulated bone morphogenic protein 4 (BMP4) expression through GPR120\u2010ERK1\/2 pathway activation in Sertoli cells and restored spermatogonia proliferation and differentiation. Our study provides evidence that omega\u20103 PUFAs metabolite 12\u2010HEPE effectively protects spermatogonia and reveals that GPR120 might be a tractable pharmacological target for fertility in men received chemotherapy or severe spermatogenesis dysfunction.<\/jats:p>","DOI":"10.1111\/cpr.13551","type":"journal-article","created":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T06:24:11Z","timestamp":1695623051000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Omega\u20103 polyunsaturated fatty acids and its metabolite <scp>12\u2010HEPE<\/scp> rescue busulfan disrupted spermatogenesis via target to <scp>GPR120<\/scp>"],"prefix":"10.1111","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0877-7925","authenticated-orcid":false,"given":"Jun","family":"Jing","sequence":"first","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University  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