{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T23:08:04Z","timestamp":1767568084174,"version":"3.48.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","content-domain":{"domain":["rep.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:p>Autophagy and apoptosis are interlocked in an extensive crosstalk. Our previous study demonstrated that hypotonic hypoxia induced marked apoptosis of a spermatocyte-derived cell line (GC-2). However, whether hypoxia-induced apoptosis is mediated by inhibition of autophagy under hypoxic conditions remains unclear. In this study, GC-2 cells were cultured in 1% O2 and harvested at different time points. Autophagy was determined by acridine orange staining, cyto-ID staining, mCherry-GFP-LC3B adenovirus transfection and Western blotting for various autophagy markers. Apoptosis was detected by TUNEL staining, flow cytometry, JC-1 staining and Western blotting of apoptosis-related proteins. We found that hypoxia induced apoptosis of GC-2 cells through mitochondrial and death receptor pathways and inhibited autophagic flux in GC-2 cells in a time-dependent manner. However, while marked autolysosome formation was observed in GC-2 cells before 24 h culture in hypoxic conditions, apparent apoptosis was observed only after 24 h culture in hypoxic conditions. Caspase-8 siRNA treatment induced cell survival, accompanied by induction of the mature autophagosome, acidic vesicular organelle formation and autophagic flux. Furthermore, Beclin-1 overexpression markedly attenuated the impairment of spermatogenesis in mice by inhibiting apoptosis of spermatocytes. The results of this study demonstrate that hypoxia inhibits autophagy, which further enhances hypoxia-induced apoptosis of mouse spermatocytes by promoting caspase-8 activation in a time-dependent manner, suggesting that combined application of apoptosis inhibition and autophagy activation might be a therapeutic strategy for treating hypoxia-induced male infertility.<\/jats:p>","DOI":"10.1530\/rep-18-0243","type":"journal-article","created":{"date-parts":[[2018,10,5]],"date-time":"2018-10-05T07:29:03Z","timestamp":1538724543000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-11","source":"Crossref","is-referenced-by-count":4,"title":["Elevation of autophagy rescues spermatogenesis by inhibiting apoptosis of mouse spermatocytes"],"prefix":"10.1093","author":[{"given":"Jun","family":"Yin","sequence":"first","affiliation":[{"name":"J Yin, Department of Pathophysiology, Third Military Medical University, Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Ni","sequence":"additional","affiliation":[{"name":"B Ni, Department of Pathophysiology, Third Military Medical University, Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-dong","family":"Yang","sequence":"additional","affiliation":[{"name":"Y Yang, Institute of Medicine and Hygienic Equipment for High Altitude Region, Third Military Medical University, Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhong-wei","family":"Tang","sequence":"additional","affiliation":[{"name":"Z Tang, Department of Pathophysiology, Third Military Medical University, Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-qi","family":"Gao","sequence":"additional","affiliation":[{"name":"Z Gao, Department of Pathophysiology, Third Military Medical University, Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lan","family":"Feng","sequence":"additional","affiliation":[{"name":"L Feng, Institute of Medicine and Hygienic Equipment for High Altitude Region, Third Military Medical University, Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-gong","family":"Liao","sequence":"additional","affiliation":[{"name":"W Liao, Department of Pathophysiology, Third Military Medical University, Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqi","family":"Gao","sequence":"additional","affiliation":[{"name":"Y Gao, Institute of Medicine and Hygienic Equipment for High Altitude Region, Third Military Medical University, Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","container-title":["Reproduction"],"original-title":[],"link":[{"URL":"https:\/\/rep.bioscientifica.com\/view\/journals\/rep\/aop\/rep-18-0243\/rep-18-0243.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/rep.bioscientifica.com\/downloadpdf\/journals\/rep\/aop\/rep-18-0243\/rep-18-0243.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T23:02:04Z","timestamp":1767567724000},"score":1,"resource":{"primary":{"URL":"https:\/\/rep.bioscientifica.com\/view\/journals\/rep\/aop\/rep-18-0243\/rep-18-0243.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1530\/rep-18-0243","relation":{},"ISSN":["1470-1626","1741-7899"],"issn-type":[{"type":"print","value":"1470-1626"},{"type":"electronic","value":"1741-7899"}],"subject":[],"published":{"date-parts":[[2018,10]]}}}