{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:38:42Z","timestamp":1788849522633,"version":"build-2803163510"},"reference-count":56,"publisher":"Bioscientifica","issue":"3","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:p>The expression of vaspin and GRP78 has been shown in the testis and ovary. The postnatal testis undergoes several changes in the expression of different proteins. The expression of vaspin and GRP78 has not been shown in the postnatal testis. It has also been shown that modulation of adipokine function could affect testicular germ cell proliferation and apoptosis. Whether vaspin regulates testicular proliferation and apoptosis in the early pubertal stage is still unknown. The aim of this study was to determine the expression of vaspin\/GRP78 in postnatal testes of mice. Next, we investigated the effects of vaspin on cell proliferation and cell death (apoptosis, ferroptosis, and autophagy) in the pubertal testis. Immunohistochemistry and western blot analyses revealed that vaspin and GRP78 exhibit dynamic expression levels through developmental stages. In the testis, both proteins showed mild to moderate immunostaining in Leydig cells at early stages (PND7 and 14), with increasing intensity at PND21 and 42 in Leydig cells and spermatocytes, and round and elongated spermatids. The expression of vaspin and GRP78 was significantly down-regulated at postnatal day 21 (PND21). Moreover, exogenous vaspin treatment (PND21 to PND35) suppressed germ cell proliferation (BrdU labelling, PCNA, and GCNA) and apoptosis (decreased expression of active caspase-3 and TNF\u03b1) in the testis. The marker of autophagy, LAMP2, was elevated by vaspin treatment. Furthermore, vaspin treatment showed both stimulatory and inhibitory effects on markers of ferroptosis. In conclusion, vaspin\/GRP78 could be a new regulator of cell proliferation and cell death in pubertal mouse testes.<\/jats:p>","DOI":"10.1530\/joe-25-0208","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T10:49:34Z","timestamp":1755773374000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":2,"title":["Exogenous vaspin suppresses germ cell proliferation, apoptosis, and promotes autophagy in pubertal mouse testes"],"prefix":"10.1530","volume":"266","author":[{"given":"Preethi","family":"Riba","sequence":"first","affiliation":[{"name":"Department of Zoology, Mizoram University , , ,","place":["Aizawl, Mizoram, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guruswami","family":"Gurusubramanian","sequence":"additional","affiliation":[{"name":"Department of Zoology, Mizoram University , , ,","place":["Aizawl, Mizoram, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8973-5529","authenticated-orcid":true,"given":"Vikas Kumar","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Zoology, Mizoram University , , ,","place":["Aizawl, Mizoram, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"2026070806130122700_bib1","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.vascn.2008.12.002","article-title":"Flow cytometric analysis of BrdU incorporation as a high-throughput method for measuring adult neurogenesis in the mouse","volume":"59","author":"Balu","year":"2009","journal-title":"J Pharmacol Toxicol Methods"},{"key":"2026070806130122700_bib2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3389\/fcell.2018.00065","article-title":"Apoptosis is a demanding selective tool during the development of fetal male germ cells","volume":"6","author":"Bejarano","year":"2018","journal-title":"Front Cell Dev Biol"},{"key":"2026070806130122700_bib3","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1530\/JOE-20-0550","article-title":"Vaspin, a novel adipokine in woman granulosa cells physiology and PCOS pathogenesis?","volume":"249","author":"Bongrani","year":"2021","journal-title":"J Endocrinol"},{"key":"2026070806130122700_bib4","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal Biochem"},{"key":"2026070806130122700_bib5","doi-asserted-by":"crossref","first-page":"4439","DOI":"10.3390\/ijms21124439","article-title":"Flutamide alters the expression of chemerin, apelin, and vaspin and their respective receptors in the testes of adult rats","volume":"21","author":"Brzoskwinia","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2026070806130122700_bib6","first-page":"979","article-title":"Vaspin and amylin are expressed in human and rat placenta and regulated by nutritional status","volume":"24","author":"Caminos","year":"2009","journal-title":"Histol Histopathol"},{"key":"2026070806130122700_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.jsbmb.2022.106178","article-title":"Postnatal developmental expression of apelin receptor proteins and its role in juvenile mice testis","volume":"224","author":"Das","year":"2022","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2026070806130122700_bib10","doi-asserted-by":"crossref","DOI":"10.1016\/j.npep.2023.102354","article-title":"Apelin receptor antagonist (ML221) treatment has a stimulatory effect on the testicular proliferation, antioxidants system and steroidogenesis in adult mice","volume":"101","author":"Das","year":"2023","journal-title":"Neuropeptides"},{"key":"2026070806130122700_bib11","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1093\/molehr\/gax054","article-title":"Evaluation of apoptotic- and autophagic-related protein expressions before and after IVM of fresh, slow-frozen and vitrified pre-pubertal mouse testicular tissue","volume":"23","author":"Dumont","year":"2017","journal-title":"Mol Hum Reprod"},{"key":"2026070806130122700_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.reprotox.2024.108758","article-title":"Multi-omics revealed activation of TNF-\u03b1 induced apoptosis signaling pathway in testis of DEHP treated prepubertal male rat","volume":"132","author":"Fang","year":"2025","journal-title":"Reprod Toxicol"},{"key":"2026070806130122700_bib13","doi-asserted-by":"crossref","first-page":"10610","DOI":"10.1073\/pnas.0504703102","article-title":"Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity","volume":"102","author":"Hida","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026070806130122700_bib14","doi-asserted-by":"crossref","first-page":"176","DOI":"10.3389\/fendo.2012.00176","article-title":"Germ cell development in the postnatal testis: the key to prevent malignancy in cryptorchidism?","volume":"3","author":"Hutson","year":"2013","journal-title":"Front Endocrinol"},{"key":"2026070806130122700_bib15","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1111\/apha.12636","article-title":"Vaspin prevents elevation of blood pressure through inhibition of peripheral vascular remodelling in spontaneously hypertensive rats","volume":"217","author":"Kameshima","year":"2016","journal-title":"Acta Physiol"},{"key":"2026070806130122700_bib16","doi-asserted-by":"crossref","first-page":"147","DOI":"10.3109\/03008207.2012.761978","article-title":"Vaspin attenuates RANKL-induced osteoclast formation in RAW264.7 cells","volume":"54","author":"Kamio","year":"2013","journal-title":"Connect Tissue Res"},{"key":"2026070806130122700_bib17","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1097\/FJC.0000000000000562","article-title":"Vaspin prevents tumor necrosis factor-\u03b1\u2013induced apoptosis in cardiomyocytes by promoting autophagy","volume":"77","author":"Ke","year":"2018","journal-title":"J Cardiovasc Pharmacol"},{"key":"2026070806130122700_bib18","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1007\/s00125-011-2137-1","article-title":"Central vaspin administration acutely reduces food intake and has sustained blood glucose-lowering effects","volume":"54","author":"Kl\u00f6ting","year":"2011","journal-title":"Diabetologia"},{"key":"2026070806130122700_bib19","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1159\/000513725","article-title":"Ambivalent effects of tumor necrosis factor alpha on apoptosis of malignant and normal human keratinocytes","volume":"34","author":"Kokolakis","year":"2021","journal-title":"Skin Pharmacol Physiol"},{"key":"2026070806130122700_bib20","doi-asserted-by":"crossref","first-page":"5816","DOI":"10.3390\/ijms20225816","article-title":"In vitro effects of vaspin on porcine granulosa cell proliferation, cell cycle progression, and apoptosis by activation of GRP78 receptor and several kinase signaling pathways including MAP3\/1, AKT, and STAT3","volume":"20","author":"Kurowska","year":"2019","journal-title":"Int J Mol Sci"},{"key":"2026070806130122700_bib21","doi-asserted-by":"crossref","first-page":"6823","DOI":"10.3390\/ijms21186823","article-title":"Novel insights on the corpus luteum function: role of vaspin on porcine luteal cell angiogenesis, proliferation and apoptosis by activation of GRP78 receptor and MAP3\/1 kinase pathways","volume":"21","author":"Kurowska","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2026070806130122700_bib22","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1002\/bies.10329","article-title":"Apoptosis-an introduction","volume":"25","author":"Lawen","year":"2003","journal-title":"Bioessays"},{"key":"2026070806130122700_bib23","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/S0968-0004(01)01908-9","article-title":"The glucose-regulated proteins: stress induction and clinical applications","volume":"26","author":"Lee","year":"2001","journal-title":"Trends Biochem Sci"},{"key":"2026070806130122700_bib24","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1038\/cdd.2008.81","article-title":"The unfolded protein response regulator GRP78\/BiP is required for endoplasmic reticulum integrity and stress-induced autophagy in mammalian cells","volume":"15","author":"Li","year":"2008","journal-title":"Cell Death Differ"},{"key":"2026070806130122700_bib25","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.atherosclerosis.2013.02.013","article-title":"Vaspin attenuates high glucose-induced vascular smooth muscle cells proliferation and chemokinesis by inhibiting the MAPK, PI3K\/Akt, and NF-\u03baB signaling pathways","volume":"228","author":"Li","year":"2013","journal-title":"Atherosclerosis"},{"key":"2026070806130122700_bib26","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.3892\/mmr.2015.4708","article-title":"Vaspin attenuates the progression of atherosclerosis by inhibiting ER stress-induced macrophage apoptosis in apoE-\/- mice","volume":"13","author":"Lin","year":"2016","journal-title":"Mol Med Rep"},{"key":"2026070806130122700_bib27","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1177\/1535370214565081","article-title":"Vaspin promotes 3T3-L1 preadipocyte differentiation","volume":"240","author":"Liu","year":"2015","journal-title":"Exp Biol Med"},{"key":"2026070806130122700_bib28","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1016\/j.biocel.2004.04.011","article-title":"Apoptosis, autophagy, and more","volume":"36","author":"Lockshin","year":"2004","journal-title":"Int J Biochem Cell Biol"},{"key":"2026070806130122700_bib29","doi-asserted-by":"crossref","first-page":"5688","DOI":"10.1128\/MCB.00779-06","article-title":"GRP78\/BiP is required for cell proliferation and protecting the inner cell mass from apoptosis during early mouse embryonic development","volume":"26","author":"Luo","year":"2006","journal-title":"Mol Cell Biol"},{"key":"2026070806130122700_bib30","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.3390\/cells9112523","article-title":"Role of selective autophagy in spermatogenesis and male fertility","volume":"9","author":"Lv","year":"2020","journal-title":"Cells"},{"key":"2026070806130122700_bib46","first-page":"197","volume-title":"Mammalian Endocrinology and Male Reproductive Biology","author":"Majumder","year":"2015"},{"key":"2026070806130122700_bib31","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1530\/REP-11-0245","article-title":"Postnatal testicular development in mouse species with different levels of sperm competition","volume":"143","author":"Montoto","year":"2012","journal-title":"Reproduction"},{"key":"2026070806130122700_bib32","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0162977","article-title":"Up-regulated expression of LAMP2 and autophagy activity during neuroendocrine differentiation of prostate cancer LNCaP cells","volume":"11","author":"Morell","year":"2016","journal-title":"PLoS One"},{"key":"2026070806130122700_bib33","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1161\/CIRCRESAHA.111.300049","article-title":"Visceral adipose tissue-derived serine proteinase inhibitor inhibits apoptosis of endothelial cells as a ligand for the cell-surface GRP78\/voltage-dependent anion channel complex","volume":"112","author":"Nakatsuka","year":"2013","journal-title":"Circ Res"},{"key":"2026070806130122700_bib35","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1042\/BJ20101569","article-title":"Beyond the endoplasmic reticulum: atypical GRP78 in cell viability, signalling and therapeutic targeting","volume":"434","author":"Ni","year":"2011","journal-title":"Biochem J"},{"key":"2026070806130122700_bib36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-016-0028-x","article-title":"Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness","volume":"7","author":"Nishita","year":"2017","journal-title":"Sci Rep"},{"key":"2026070806130122700_bib37","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1152\/physrev.00025.2011","article-title":"The germline stem cell niche unit in mammalian testes","volume":"92","author":"Oatley","year":"2012","journal-title":"Physiol Rev"},{"key":"2026070806130122700_bib38","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.phrs.2011.06.001","article-title":"Vaspin prevents TNF-\u03b1-induced intracellular adhesion molecule-1 via inhibiting reactive oxygen species-dependent NF-\u03baB and PKC\u03b8 activation in cultured rat vascular smooth muscle cells","volume":"64","author":"Phalitakul","year":"2011","journal-title":"Pharmacol Res"},{"key":"2026070806130122700_bib39","first-page":"831","article-title":"New insights into cell apoptosis and proliferation: the potential role of vaspin","volume":"72","author":"Pich","year":"2021","journal-title":"J Physiol Pharmacol"},{"key":"2026070806130122700_bib40","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.bbamcr.2010.10.010","article-title":"Anti-apoptosis and cell survival: a review","volume":"1813","author":"Portt","year":"2011","journal-title":"Biochim Biophys Acta"},{"key":"2026070806130122700_bib41","doi-asserted-by":"crossref","DOI":"10.1016\/j.jsbmb.2023.106306","article-title":"Evidence of the inhibitory role of visfatin in the testicular activity of mice during the infantile stage","volume":"231","author":"Rempuia","year":"2023","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2026070806130122700_bib59","doi-asserted-by":"crossref","DOI":"10.1111\/jne.70044","article-title":"Exogenous visfatin suppresses pituitary gonadotrophins and stimulates testosterone secretion in a male mouse","volume":"37","author":"Rempuia","year":"2025","journal-title":"J Neuroendocrinol"},{"key":"2026070806130122700_bib42","doi-asserted-by":"crossref","DOI":"10.1111\/and.14602","article-title":"Interaction between apoptosis and autophagy in testicular function","volume":"54","author":"Rotimi","year":"2022","journal-title":"Andrologia"},{"key":"2026070806130122700_bib43","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1095\/biolreprod66.4.950","article-title":"Bax-dependent spermatogonia apoptosis is required for testicular development and spermatogenesis","volume":"66","author":"Russell","year":"2002","journal-title":"Biol Reprod"},{"key":"2026070806130122700_bib44","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.3390\/ijms19061732","article-title":"Anti-atherogenic effects of vaspin on human aortic smooth muscle cell\/macrophage responses and hyperlipidemic mouse plaque phenotype","volume":"19","author":"Sato","year":"2018","journal-title":"Int J Mol Sci"},{"key":"2026070806130122700_bib45","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1098\/rstb.2009.0124","article-title":"Male germ cell apoptosis: regulation and biology","volume":"365","author":"Shaha","year":"2010","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"2026070806130122700_bib47","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0960-0760(03)00193-6","article-title":"Deciphering the pathways of germ cell apoptosis in the testis","volume":"85","author":"Sinha Hikim","year":"2003","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2026070806130122700_bib48","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s40360-019-0334-6","article-title":"The adipokine vaspin reduces apoptosis in human hepatocellular carcinoma (Hep-3B) cells, associated with lower levels of NO and superoxide anion","volume":"20","author":"Skonieczna","year":"2019","journal-title":"BMC Pharmacol Toxicol"},{"key":"2026070806130122700_bib49","doi-asserted-by":"crossref","first-page":"R69","DOI":"10.1530\/EC-17-0382","article-title":"Cancer treatment in childhood and testicular function: the importance of the somatic environment","volume":"7","author":"Stukenborg","year":"2018","journal-title":"Endocr Connect"},{"key":"2026070806130122700_bib50","volume-title":"Testes and Ovaries \u2013 Functional and Clinical Differences and Similarities","author":"Tang","year":"2017"},{"key":"2026070806130122700_bib51","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1080\/21623945.2021.1910154","article-title":"Cleavage of the vaspin N-terminus releases cell-penetrating peptides that affect early stages of adipogenesis and inhibit lipolysis in mature adipocytes","volume":"10","author":"Tindall","year":"2021","journal-title":"Adipocyte"},{"key":"2026070806130122700_bib52","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.2147\/DDDT.S199459","article-title":"Role of GRP78 inhibiting artesunate-induced ferroptosis in KRAS mutant pancreatic cancer cells","volume":"13","author":"Wang","year":"2019","journal-title":"Drug Des Dev Ther"},{"key":"2026070806130122700_bib53","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12986-020-0429-5","article-title":"Vaspin antagonizes high fat-induced bone loss in rats and promotes osteoblastic differentiation in primary rat osteoblasts through Smad-Runx2 signaling pathway","volume":"17","author":"Wang","year":"2020","journal-title":"Nutr Metab"},{"key":"2026070806130122700_bib54","doi-asserted-by":"crossref","DOI":"10.1016\/j.envpol.2023.121434","article-title":"Cadmium exposure during puberty damages testicular development and spermatogenesis via ferroptosis caused by intracellular iron overload and oxidative stress in mice","volume":"325","author":"Wang","year":"2023","journal-title":"Environ Pollut"},{"key":"2026070806130122700_bib55","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1038\/sj.onc.1204254","article-title":"Differential expression and regulation of the retinoblastoma family of proteins during testicular development and spermatogenesis: roles in the control of germ cell proliferation, differentiation and apoptosis","volume":"20","author":"Yan","year":"2001","journal-title":"Oncogene"},{"key":"2026070806130122700_bib56","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1095\/biolreprod.116.144063","article-title":"Regulatory effects of autophagy on spermatogenesis","volume":"96","author":"Yin","year":"2017","journal-title":"Biol Reprod"},{"key":"2026070806130122700_bib57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2022\/1149582","article-title":"Vaspin alleviates sepsis-induced cardiac injury and cardiac inflammation by inhibiting kallikrein 7 in mice","volume":"2022","author":"Yin","year":"2022","journal-title":"Mediat Inflamm"},{"key":"2026070806130122700_bib58","doi-asserted-by":"crossref","first-page":"3244","DOI":"10.1128\/MCB.21.9.3244-3255.2001","article-title":"Control of spermatogenesis in mice by the cyclin D-dependent kinase inhibitors p18Ink4c and p19Ink4d","volume":"21","author":"Zindy","year":"2001","journal-title":"Mol Cell Biol"}],"container-title":["Journal of Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/266\/3\/JOE-25-0208.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/downloadpdf\/journals\/joe\/266\/3\/JOE-25-0208.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/joe\/article-pdf\/doi\/10.1530\/JOE-25-0208\/45086\/joe-25-0208.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/joe\/article-pdf\/doi\/10.1530\/JOE-25-0208\/45086\/joe-25-0208.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T10:13:16Z","timestamp":1783505596000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/joe\/article\/266\/3\/e250208\/5740\/Exogenous-vaspin-suppresses-germ-cell"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,21]]},"references-count":56,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,9,1]]}},"URL":"https:\/\/doi.org\/10.1530\/joe-25-0208","relation":{},"ISSN":["1479-6805","0022-0795"],"issn-type":[{"value":"1479-6805","type":"electronic"},{"value":"0022-0795","type":"print"}],"subject":[],"published":{"date-parts":[[2025,8,21]]},"article-number":"e250208"}}