{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T08:03:39Z","timestamp":1767859419778,"version":"3.49.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T00:00:00Z","timestamp":1425340800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T00:00:00Z","timestamp":1425340800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although previous studies have suggested that cumulus cells (CCs) accelerate oocyte aging by secreting soluble and heat-sensitive paracrine factors, the factors involved are not well characterized. Because Fas-mediated apoptosis represents a major pathway in induction of apoptosis in various cells, we proposed that CCs facilitate oocyte aging by releasing soluble Fas ligand (sFasL). In this study, we reported that when the aging of freshly ovulated mouse oocytes were studied <jats:italic>in vitro<\/jats:italic>, both the apoptotic rates of CCs and the amount of CCs produced sFasL increased significantly with the culture time. We found that oocytes expressed stable levels of Fas receptors up to 24\u2005h of <jats:italic>in vitro<\/jats:italic> aging. Moreover, culture of cumulus-denuded oocytes in CCs-conditioned CZB medium (CM), in CZB supplemented with recombinant sFasL, or in CM containing sFasL neutralizing antibodies all showed that sFasL impaired the developmental potential of the oocytes whereas facilitating activation and fragmentation of aging oocytes. Furthermore, CCs from the <jats:italic>FasL<\/jats:italic>-defective gld mice did not accelerate oocyte aging due to the lack of functional FasL. In conclusion, we propose that CCs surrounding aging oocytes released sFasL in an apoptosis-related manner and the released sFasL accelerated oocyte aging by binding to Fas receptors.<\/jats:p>","DOI":"10.1038\/srep08683","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T10:18:10Z","timestamp":1425377890000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Cumulus cells accelerate oocyte aging by releasing soluble Fas Ligand in mice"],"prefix":"10.1038","volume":"5","author":[{"given":"Jiang","family":"Zhu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian-Yang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuan-Xin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Jiu","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing-He","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,3,3]]},"reference":[{"key":"BFsrep08683_CR1","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1002\/jez.1401480303","volume":"148","author":"R Yanagimachi","year":"1961","unstructured":"Yanagimachi, R. & Chang, M. C. Fertilizable life of golden hamster ova and their morphological changes at the time of losing fertilizability. J Exp Zool 148, 185\u2013203 (1961).","journal-title":"J Exp Zool"},{"key":"BFsrep08683_CR2","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/0014-4827(78)90371-3","volume":"113","author":"DG Whittingham","year":"1978","unstructured":"Whittingham, D. G. & Siracusa, G. The involvement of calcium in the activation of mammalian oocytes. Exp Cell Res 113, 311\u2013317 (1978).","journal-title":"Exp Cell Res"},{"key":"BFsrep08683_CR3","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1002\/mrd.1120030409","volume":"3","author":"FJ Longo","year":"1980","unstructured":"Longo, F. J. Aging of mouse eggs in vivo and in vitro. Gamete Res 3, 379\u2013393 (1980).","journal-title":"Gamete Res"},{"key":"BFsrep08683_CR4","first-page":"131","volume":"95","author":"M Webb","year":"1986","unstructured":"Webb, M., Howlett, S. K. & Maro, B. Parthenogenesis and cytoskeletal organization in aging mouse eggs. J Embryol Exp Morphol 95, 131\u2013145 (1986).","journal-title":"J Embryol Exp Morphol"},{"key":"BFsrep08683_CR5","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1093\/humrep\/13.2.381","volume":"13","author":"JJ Tarin","year":"1998","unstructured":"Tarin, J. J., Ten, J., Vendrell, F. J. & Cano, A. Dithiothreitol prevents age associated decrease in oocyte\/conceptus viability in vitro. Hum Reprod 13, 381\u2013386 (1998).","journal-title":"Hum Reprod"},{"key":"BFsrep08683_CR6","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1095\/biolreprod.105.043703","volume":"73","author":"YL Miao","year":"2005","unstructured":"Miao, Y. L. et al. Cumulus cells accelerate aging of mouse oocytes. Biol Reprod 73, 1025\u20131031 (2005).","journal-title":"Biol Reprod"},{"key":"BFsrep08683_CR7","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1002\/mrd.1120080303","volume":"8","author":"J Juetten","year":"1983","unstructured":"Juetten, J. & Bavister, B. D. Effects of egg aging on in vitro fertilization and first cleavage division in the hamster. Gamete Res 8, 219\u2013230 (1983).","journal-title":"Gamete Res"},{"key":"BFsrep08683_CR8","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1093\/oxfordjournals.humrep.a138235","volume":"8","author":"J Tesarik","year":"1993","unstructured":"Tesarik, J. Subzonal sperm insertion with aged human oocytes from failed in vitro fertilization attempts: fertilization results and some applications. Hum Reprod 8, 1245\u20131250 (1993).","journal-title":"Hum Reprod"},{"key":"BFsrep08683_CR9","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1093\/oxfordjournals.humrep.a138084","volume":"8","author":"NJ Winston","year":"1993","unstructured":"Winston, N. J., Braude, P. R. & Johnson, M. H. Are failed-fertilized human oocytes useful? Hum Reprod 8, 503\u2013507 (1993).","journal-title":"Hum Reprod"},{"key":"BFsrep08683_CR10","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1095\/biolreprod61.5.1347","volume":"61","author":"JJ Tarin","year":"1999","unstructured":"Tarin, J. J. et al. Long-term effects of postovulatory aging of mouse oocytes on offspring: a two-generational study. Biol Reprod 61, 1347\u20131355 (1999).","journal-title":"Biol Reprod"},{"key":"BFsrep08683_CR11","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1095\/biolreprod66.2.495","volume":"66","author":"JJ Tarin","year":"2002","unstructured":"Tarin, J. J., Perez-Albala, S., Perez-Hoyos, S. & Cano, A. Postovulatory aging of oocytes decreases reproductive fitness and longevity of offspring. Biol Reprod 66, 495\u2013499 (2002).","journal-title":"Biol Reprod"},{"key":"BFsrep08683_CR12","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/1477-7827-6-58","volume":"6","author":"O Lacham-Kaplan","year":"2008","unstructured":"Lacham-Kaplan, O. & Trounson, A. Reduced developmental competence of immature, in-vitro matured and postovulatory aged mouse oocytes following IVF and ICSI. Reprod Biol Endocrinol 6, 58 (2008).","journal-title":"Reprod Biol Endocrinol"},{"key":"BFsrep08683_CR13","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1017\/S0967199403002181","volume":"11","author":"RP Cervera","year":"2003","unstructured":"Cervera, R. P. & Garc\u0131'a-Xime'nez, F. Oocyte age and nuclear donor cell type affect the technical efficiency of somatic cloning in rabbits. Zygote 11, 151\u2013158 (2003).","journal-title":"Zygote"},{"key":"BFsrep08683_CR14","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1017\/S0967199405003370","volume":"13","author":"M Iwamoto","year":"2005","unstructured":"Iwamoto, M. et al. Effects of caffeine treatment on aged porcine oocytes: parthenogenetic activation ability, chromosome condensation and development to the blastocyst stage after somatic cell nuclear transfer. Zygote 13, 335\u2013345 (2005).","journal-title":"Zygote"},{"key":"BFsrep08683_CR15","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1089\/clo.2006.0023","volume":"9","author":"YG Wu","year":"2007","unstructured":"Wu, Y. G. et al. The effects of delayed activation and MG132 treatment on nuclear remodeling and preimplantation development of embryos cloned by electrofusion are correlated with the age of recipient cytoplasts. Cloning Stem Cells 9, 417\u2013431 (2007).","journal-title":"Cloning Stem Cells"},{"key":"BFsrep08683_CR16","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1002\/ar.1091790104","volume":"179","author":"FJ Longo","year":"1974","unstructured":"Longo, F. J. An ultrastructural analysis of spontaneous activation of hamster eggs aged in vivo. Anat Rec 179, 27\u201355 (1974).","journal-title":"Anat Rec"},{"key":"BFsrep08683_CR17","first-page":"1","volume":"16","author":"JH Tan","year":"1985","unstructured":"Tan, J. H. An ultrastructural study on the pig oocyte during its aging after ovulation. Acta Vet Zootech Sinica 16, 1\u20134 (1985).","journal-title":"Acta Vet Zootech Sinica"},{"key":"BFsrep08683_CR18","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/0012-1606(82)90314-1","volume":"89","author":"JJ Eppig","year":"1982","unstructured":"Eppig, J. J. The relationship between cumulus cell-oocyte coupling, oocyte meiotic maturation and cumulus expansion. Dev Biol 89, 268\u2013272 (1982).","journal-title":"Dev Biol"},{"key":"BFsrep08683_CR19","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1002\/bies.950131105","volume":"13","author":"JJ Eppig","year":"1991","unstructured":"Eppig, J. J. Intercommunication between mammalian oocytes and companion somatic cells. Bioessays 13, 569\u2013574 (1991).","journal-title":"Bioessays"},{"key":"BFsrep08683_CR20","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1095\/biolreprod43.4.543","volume":"43","author":"R Buccione","year":"1990","unstructured":"Buccione, R., Schroeder, A. C. & Eppig, J. J. Interactions between somatic cells and germ cells throughout mammalian oogenesis. Biol Reprod 43, 543\u2013547 (1990).","journal-title":"Biol Reprod"},{"key":"BFsrep08683_CR21","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1002\/mrd.10102","volume":"61","author":"S Tanghe","year":"2002","unstructured":"Tanghe, S., Van Soom, A., Nauwynck, H., Coryn, M. & de Kruif, A. Minireview: functions of the cumulus oophorus during oocyte maturation, ovulation and fertilization. Mol Reprod Dev 61, 414\u2013424 (2002).","journal-title":"Mol Reprod Dev"},{"key":"BFsrep08683_CR22","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1002\/mrd.20779","volume":"75","author":"TW Qiao","year":"2008","unstructured":"Qiao, T. W. et al. Cumulus cells accelerate aging of mouse oocytes by secreting a soluble factor(s). Mol Reprod Devel 75, 521\u2013528 (2008).","journal-title":"Mol Reprod Devel"},{"key":"BFsrep08683_CR23","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1530\/REP-09-0122","volume":"138","author":"N Liu","year":"2009","unstructured":"Liu, N. et al. Pyruvate prevents aging of mouse oocytes. Reproduction 138, 223\u2013234 (2009).","journal-title":"Reproduction"},{"key":"BFsrep08683_CR24","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1016\/j.theriogenology.2011.06.016","volume":"76","author":"Y Wu","year":"2011","unstructured":"Wu, Y. et al. BIM EL-mediated apoptosis in cumulus cells contributes to degenerative changes in aged porcine oocytes via a paracrine action. Theriogenology 76, 1487\u20131495 (2011).","journal-title":"Theriogenology"},{"key":"BFsrep08683_CR25","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1084\/jem.182.6.1777","volume":"182","author":"N Kayagaki","year":"1995","unstructured":"Kayagaki, N. et al. Metalloproteinase-mediated release of human Fas ligand. J Exp Med 182, 1777\u20131783 (1995).","journal-title":"J Exp Med"},{"key":"BFsrep08683_CR26","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1002\/j.1460-2075.1995.tb07096.x","volume":"14","author":"M Tanaka","year":"1995","unstructured":"Tanaka, M., Suda, T., Takahashi, T. & Nagata, S. Expression of the functional soluble form of human fas ligand in activated lymphocytes. EMBO J 14, 1129\u20131135 (1995).","journal-title":"EMBO J"},{"key":"BFsrep08683_CR27","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1016\/S0002-9440(10)65708-2","volume":"153","author":"N Mitsiades","year":"1998","unstructured":"Mitsiades, N., Poulaki, V., Kotoula, V., Leone, A. & Tsokos, M. Fas ligand is present in tumors of the Ewing's sarcoma family and is cleaved into a soluble form by a metalloproteinase. Am J Pathol 153, 1947\u20131956 (1998).","journal-title":"Am J Pathol"},{"key":"BFsrep08683_CR28","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/0092-8674(91)90614-5","volume":"66","author":"N Itoh","year":"1991","unstructured":"Itoh, N. et al. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 66, 233\u2013243 (1991).","journal-title":"Cell"},{"key":"BFsrep08683_CR29","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1038\/373438a0","volume":"373","author":"J Dhein","year":"1995","unstructured":"Dhein, J., Walczak, H., Baumler, C., Debatin, K. M. & Krammer, P. H. Autocrine T-cell suicide mediated by APO-1\/(Fas\/CD95). Nature 373, 438\u2013441 (1995).","journal-title":"Nature"},{"key":"BFsrep08683_CR30","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1038\/373444a0","volume":"373","author":"ST Ju","year":"1995","unstructured":"Ju, S. T. et al. Fas(CD95)\/FasL interactions required for programmed cell death after T-cell activation. Nature 373, 444\u2013448 (1995).","journal-title":"Nature"},{"key":"BFsrep08683_CR31","first-page":"561","volume":"16","author":"R Matsumura","year":"1998","unstructured":"Matsumura, R. et al. Glandular and extraglandular expression of the Fas-Fas ligand and apoptosis in patients with Sj\u00f6gren's syndrome. Clin Exp Rheumatol 16, 561\u2013568 (1998).","journal-title":"Clin Exp Rheumatol"},{"key":"BFsrep08683_CR32","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1054\/drup.2001.0210","volume":"4","author":"V Poulaki","year":"2001","unstructured":"Poulaki, V., Mitsiades, C. S. & Mitsiades, N. The role of Fas and FasL as mediators of anticancer chemotherapy. Drug Resist Updat 4, 233\u2013242 (2001).","journal-title":"Drug Resist Updat"},{"key":"BFsrep08683_CR33","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1530\/rep.0.1260783","volume":"126","author":"SJ Dharma","year":"2003","unstructured":"Dharma, S. J., Kelkar, R. L. & Nandedkar, T. D. Fas and Fas ligand protein and mRNA in normal and atretic mouse ovarian follicles. Reproduction 126, 783\u2013789 (2003).","journal-title":"Reproduction"},{"key":"BFsrep08683_CR34","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1095\/biolreprod.104.028613","volume":"71","author":"FJ Rubio Pomar","year":"2004","unstructured":"Rubio Pomar, F. J. et al. Role of Fas-mediated apoptosis and follicle-stimulating hormone on the developmental capacity of bovine cumulus oocyte complexes in vitro. Biol Reprod 71, 790\u2013796 (2004).","journal-title":"Biol Reprod"},{"key":"BFsrep08683_CR35","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.theriogenology.2013.04.002","volume":"80","author":"HJ Li","year":"2013","unstructured":"Li, H. J. et al. FasL-induced apoptosis in bovine oocytes via the Bax signal. Theriogenology 80, 248\u2013255 (2013).","journal-title":"Theriogenology"},{"key":"BFsrep08683_CR36","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1016\/0092-8674(94)90375-1","volume":"76","author":"T Takahashi","year":"1994","unstructured":"Takahashi, T. et al. Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell 76, 969\u2013976 (1994).","journal-title":"Cell"},{"key":"BFsrep08683_CR37","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1530\/REP-06-0161","volume":"133","author":"M Moniruzzaman","year":"2007","unstructured":"Moniruzzaman, M., Sakamaki, K., Akazawa, Y. & Miyano, T. Oocyte growth and follicular development in KIT-deficient Fas-knockout mice. Reproduction 133, 117\u2013125 (2007).","journal-title":"Reproduction"},{"key":"BFsrep08683_CR38","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1017\/S096719949800032X","volume":"6","author":"JP Xu","year":"1998","unstructured":"Xu, J. P., Li, X., Mori, E., Guo, M. W. & Mori, T. Aberrant expression and dysfunction of Fas antigen in MRL\/MpJ-lpr\/lpr murine ovary. Zygote 6, 359\u2013367 (1998).","journal-title":"Zygote"},{"key":"BFsrep08683_CR39","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1017\/S0967199402002034","volume":"10","author":"M Guo","year":"2002","unstructured":"Guo, M. et al. Induction of apoptosis mediated by fas receptor and activation of caspase-3 in MRL-+\/+ or MRL-lpr\/lpr murine oocytes. Zygote 10, 17\u201322 (2002).","journal-title":"Zygote"},{"key":"BFsrep08683_CR40","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/0012-1606(89)90279-0","volume":"136","author":"JZ Kubiak","year":"1989","unstructured":"Kubiak, J. Z. Mouse oocytes gradually develop the capacity for activation during the metaphase II arrest. Dev Biol 136, 537\u2013545 (1989).","journal-title":"Dev Biol"},{"key":"BFsrep08683_CR41","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1002\/jez.a.62","volume":"301","author":"GC Lan","year":"2004","unstructured":"Lan, G. C. et al. Effects of posttreatment with 6-dimethylaminopurine (6-DMAP) on ethanol activation of mouse oocytes at different ages. J Exp Zool A Comp Exp Biol 301, 837\u2013843 (2004).","journal-title":"J Exp Zool A Comp Exp Biol"},{"key":"BFsrep08683_CR42","doi-asserted-by":"publisher","first-page":"1828","DOI":"10.1095\/biolreprod66.6.1828","volume":"66","author":"AC Gordo","year":"2002","unstructured":"Gordo, A. C. et al. Intracellular calcium oscillations signal apoptosis rather than activation in in vitro aged mouse eggs. Biol Reprod 66, 1828\u20131837 (2002).","journal-title":"Biol Reprod"},{"key":"BFsrep08683_CR43","doi-asserted-by":"publisher","first-page":"1438","DOI":"10.1006\/bbrc.1994.2346","volume":"203","author":"MW Guo","year":"1994","unstructured":"Guo, M. W., Mori, E., Xu, J. P. & Mori, T. Identification of Fas antigen associated with apoptotic cell death in murine ovary. Biochem Biophys Res Commun 203, 1438\u20131446 (1994).","journal-title":"Biochem Biophys Res Commun"},{"key":"BFsrep08683_CR44","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1111\/j.1600-0897.1997.tb00249.x","volume":"37","author":"MW Guo","year":"1997","unstructured":"Guo, M. W. et al. Expression of Fas ligand in murine ovary. Am J Reprod Immunol 37, 391\u2013398 (1997).","journal-title":"Am J Reprod Immunol"},{"key":"BFsrep08683_CR45","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1159\/000191295","volume":"3","author":"T Mori","year":"1997","unstructured":"Mori, T. et al. Expression of Fas-Fas ligand system associated with atresia through apoptosis in murine ovary. Horm Res 48 Suppl 3, 11\u20139 (1997).","journal-title":"Horm Res"},{"key":"BFsrep08683_CR46","doi-asserted-by":"publisher","first-page":"L298","DOI":"10.1152\/ajplung.2001.280.2.L298","volume":"280","author":"KL Serrao","year":"2001","unstructured":"Serrao, K. L., Fortenberry, J. D., Owens, M. L., Harris, F. L. & Brown, L. A. Neutrophils induce apoptosis of lung epithelial cells via release of soluble Fas ligand. Am J Physiol Lung Cell Mol Physiol 280, L298\u2013305 (2001).","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"BFsrep08683_CR47","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1016\/j.cellsig.2009.02.018","volume":"21","author":"F Zhang","year":"2009","unstructured":"Zhang, F. et al. Phospholipase A2-activating protein (PLAA) enhances cisplatin-induced apoptosis in HeLa cells. Cell Signal 21, 1085\u20131099 (2009).","journal-title":"Cell Signal"},{"key":"BFsrep08683_CR48","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.1016\/S0891-5849(02)01141-3","volume":"33","author":"TL Denning","year":"2002","unstructured":"Denning, T. L. et al. Oxidative stress induces the expression of Fas and Fas ligand and apoptosis in murine intestinal epithelial cells. Free Radic Biol Med 33, 1641\u20131650 (2002).","journal-title":"Free Radic Biol Med"},{"key":"BFsrep08683_CR49","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/S0014-5793(98)00562-6","volume":"429","author":"M Vogt","year":"1998","unstructured":"Vogt, M., Bauer, M. K., Ferrari, D. & Schulze-Osthoff, K. Oxidative stress and hypoxia\/reoxygenation trigger CD95 (APO-1\/Fas) ligand expression in microglial cells. FEBS Lett 429, 67\u201372 (1998).","journal-title":"FEBS Lett"},{"key":"BFsrep08683_CR50","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1183\/09031936.00084608","volume":"33","author":"R MacRedmond","year":"2009","unstructured":"MacRedmond, R., Singhera, G. K. & Dorscheid, D. R. Erythropoietin inhibits respiratory epithelial cell apoptosis in a model of acute lung injury. Eur Respir J 33, 1403\u20131414 (2009).","journal-title":"Eur Respir J"},{"key":"BFsrep08683_CR51","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1095\/biolreprod.104.030999","volume":"72","author":"W Ma","year":"2005","unstructured":"Ma, W. et al. Reduced expression of MAD2, BCL2 and MAP kinase activity in pig oocytes after in vitro aging are associated with defects in sister chromatid segregation during meiosis II and embryo fragmentation after activation. Biol Reprod 72, 373\u2013383 (2005).","journal-title":"Biol Reprod"},{"key":"BFsrep08683_CR52","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1095\/biolreprod.108.072017","volume":"80","author":"T Takahashi","year":"2009","unstructured":"Takahashi, T. et al. Poor embryo development in mouse oocytes aged in vitro is associated with impaired calcium homeostasis. Biol Reprod 80, 493\u2013502 (2009).","journal-title":"Biol Reprod"},{"key":"BFsrep08683_CR53","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1095\/biolreprod62.5.1370","volume":"62","author":"AC Gordo","year":"2000","unstructured":"Gordo, A. C., Wu, H., He, C. L. & Fissore, R. A. Injection of sperm cytosolic factor into mouse metaphase II oocytes induces different developmental fates according to the frequency of [Ca(2t)](i) oscillations and oocyte age. Biol Reprod 62, 1370\u20131379 (2000).","journal-title":"Biol Reprod"},{"key":"BFsrep08683_CR54","doi-asserted-by":"publisher","first-page":"2303","DOI":"10.1002\/eji.1830250828","volume":"25","author":"SM Mariani","year":"1995","unstructured":"Mariani, S. M., Matiba, B., B\u00e4umler, C. & Krammer, P. H. Regulation of cell surface APO-1\/Fas (CD95) ligand expression by metalloproteases. Eur J Immunol 25, 2303\u20132307 (1995).","journal-title":"Eur J Immunol"},{"key":"BFsrep08683_CR55","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/0022-1759(96)00051-8","volume":"193","author":"SM Mariani","year":"1996","unstructured":"Mariani, S. M., Matiba, B., Sparna, T. & Krammer, P. H. Expression of biologically active mouse and human CD95\/APO-1\/Fas ligand in the baculovirus system. J Immunol Methods 193, 63\u201370 (1996).","journal-title":"J Immunol Methods"},{"key":"BFsrep08683_CR56","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1084\/jem.187.8.1205","volume":"187","author":"P Schneider","year":"1998","unstructured":"Schneider, P. et al. Conversion of membrane-bound Fas(CD95) ligand to its soluble form is associated with downregulation of its proapoptotic activity and loss of liver toxicity. J Exp Med 187, 1205\u20131213 (1998).","journal-title":"J Exp Med"},{"key":"BFsrep08683_CR57","doi-asserted-by":"publisher","first-page":"2253","DOI":"10.1002\/eji.1830250821","volume":"25","author":"A Rensing-Ehl","year":"1995","unstructured":"Rensing-Ehl, A. et al. Local Fas\/APO-1 (CD95) ligand-mediated tumor cell killing in vivo. Eur J Immunol 25, 2253\u20132258 (1995).","journal-title":"Eur J Immunol"},{"key":"BFsrep08683_CR58","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1111\/j.1439-0531.2008.01172.x","volume":"2","author":"N Manabe","year":"2008","unstructured":"Manabe, N. et al. Role of cell death ligand and receptor system on regulation of follicular atresia in pig ovaries. Reprod Domest Anim 43 Suppl 2, 268\u2013272 (2008).","journal-title":"Reprod Domest Anim"},{"key":"BFsrep08683_CR59","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.diff.2008.12.001","volume":"77","author":"M J\u00e4\u00e4skel\u00e4inen","year":"2009","unstructured":"J\u00e4\u00e4skel\u00e4inen, M. et al. TRAIL pathway components and their putative role in granulosa cell apoptosis in the human ovary. Differentiation 77, 369\u2013376 (2009).","journal-title":"Differentiation"},{"key":"BFsrep08683_CR60","doi-asserted-by":"publisher","first-page":"2445","DOI":"10.1210\/en.2004-1472","volume":"146","author":"AS Chang","year":"2005","unstructured":"Chang, A. S., Dale, A. N. & Moley, K. H. Maternal diabetes adversely affects preovulatory oocyte maturation, development and granulosa cell apoptosis. Endocrinology 146, 2445\u20132453 (2005).","journal-title":"Endocrinology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep08683","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep08683.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep08683.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T16:55:55Z","timestamp":1672937755000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep08683"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,3]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,8,14]]}},"alternative-id":["BFsrep08683"],"URL":"https:\/\/doi.org\/10.1038\/srep08683","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,3]]},"assertion":[{"value":"19 November 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 January 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 March 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"8683"}}