{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T10:35:52Z","timestamp":1762252552438,"version":"3.37.3"},"reference-count":68,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T00:00:00Z","timestamp":1495065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"This work was supported by Lifespan Hospital System Research Funds"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0177995","type":"journal-article","created":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T19:43:49Z","timestamp":1495741429000},"page":"e0177995","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Ghrelin modulates testicular damage in a cryptorchid mouse model"],"prefix":"10.1371","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8135-9730","authenticated-orcid":true,"given":"Enrica","family":"Bianchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim","family":"Boekelheide","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Sigman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan J.","family":"Hall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2017,5,18]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"114","DOI":"10.2164\/jandrol.110.011320","article-title":"Simultaneous accumulation of hyaluronan binding protein 1 (HABP1\/p32\/gC1qR) and apoptotic induction of germ cells in cryptorchid testis","volume":"33","author":"V Kumar","year":"2012","journal-title":"J Androl"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.tice.2012.04.005","article-title":"Germ cell removal after induction of cryptorchidism in adult rats","volume":"44","author":"F Liu","year":"2012","journal-title":"Tissue Cell"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1095\/biolreprod51.5.865","article-title":"Experimentally induced cryptorchidism increases apoptosis in rat testis","volume":"51","author":"T Shikone","year":"1994","journal-title":"Biol Reprod"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1210\/en.2003-0175","article-title":"Key apoptotic pathways for heat-induced programmed germ cell death in the testis","volume":"144","author":"AP Hikim","year":"2003","journal-title":"Endocrinology"},{"key":"ref5","first-page":"47","article-title":"Effect of prolonged cryptorchidism on germ cell apoptosis and testicular sperm count","volume":"6","author":"A Barqawi","year":"2004","journal-title":"Asian J Androl"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/j.1939-4640.1999.tb02509.x","article-title":"Testis and temperature: an historical, clinical, and research perspective","volume":"20","author":"A Morgentaler","year":"1999","journal-title":"J Androl"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1095\/biolreprod61.2.393","article-title":"Role of radical oxygen species in rat testicular germ cell apoptosis induced by heat stress","volume":"61","author":"M Ikeda","year":"1999","journal-title":"Biol Reprod"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1002\/j.1939-4640.2005.tb01096.x","article-title":"Overexpression of endothelial nitric oxide synthase in transgenic mice accelerates testicular germ cell apoptosis induced by experimental cryptorchidism","volume":"26","author":"T Ishikawa","year":"2005","journal-title":"J Androl"},{"key":"ref9","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":"AP Sinha Hikim","year":"2003","journal-title":"J Steroid Biochem Mol Biol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1002\/j.1939-4640.2002.tb02336.x","article-title":"Mild testicular hyperthermia induces profound transitional spermatogenic suppression through increased germ cell apoptosis in adult cynomolgus monkeys (Macaca fascicularis)","volume":"23","author":"YH Lue","year":"2002","journal-title":"J Androl"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.bbrc.2003.10.191","article-title":"Suppression of cytochrome c release and apoptosis in testes with heat stress by minocycline","volume":"312","author":"S Matsuki","year":"2003","journal-title":"Biochem Biophys Res Commun"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/45230","article-title":"Ghrelin is a growth-hormone-releasing acylated peptide from stomach","volume":"402","author":"M Kojima","year":"1999","journal-title":"Nature"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/S1043-2760(00)00362-3","article-title":"Ghrelin: discovery of the natural endogenous ligand for the growth hormone secretagogue receptor","volume":"12","author":"M Kojima","year":"2001","journal-title":"Trends Endocrinol Metab"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1210\/mend.11.4.9908","article-title":"Molecular analysis of rat pituitary and hypothalamic growth hormone secretagogue receptors","volume":"11","author":"KK McKee","year":"1997","journal-title":"Mol Endocrinol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.jss.2015.10.044","article-title":"Ghrelin ameliorates adhesions in a postsurgical mouse model","volume":"201","author":"E Bianchi","year":"2016","journal-title":"J Surg Res"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"e0153968","DOI":"10.1371\/journal.pone.0153968","article-title":"Ghrelin Inhibits Post-Operative Adhesions via Blockage of the TGF-beta Signaling Pathway","volume":"11","author":"E Bianchi","year":"2016","journal-title":"PLoS One"},{"key":"ref17","first-page":"RA217","article-title":"Ghrelin: central and peripheral effects of a novel peptydil hormone","volume":"9","author":"M De Ambrogi","year":"2003","journal-title":"Med Sci Monit"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S0167-0115(02)00067-8","article-title":"The ghrelin cell: a novel developmentally regulated islet cell in the human pancreas","volume":"107","author":"N Wierup","year":"2002","journal-title":"Regul Pept"},{"key":"ref19","first-page":"26","article-title":"Ghrelin: novel regulator of gonadal function","volume":"28","author":"M Tena-Sempere","year":"2005","journal-title":"J Endocrinol Invest"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1210\/endo.143.2.8646","article-title":"Novel expression and functional role of ghrelin in rat testis","volume":"143","author":"M Tena-Sempere","year":"2002","journal-title":"Endocrinology"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1210\/jc.2003-031375","article-title":"Expression of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor, in normal human testis and testicular tumors","volume":"89","author":"F Gaytan","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1095\/biolreprod.102.008862","article-title":"Developmental, stage-specific, and hormonally regulated expression of growth hormone secretagogue receptor messenger RNA in rat testis","volume":"68","author":"ML Barreiro","year":"2003","journal-title":"Biol Reprod"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1016\/j.peptides.2009.09.004","article-title":"Ghrelin inhibits post-infarct myocardial remodeling and improves cardiac function through anti-inflammation effect","volume":"30","author":"CX Huang","year":"2009","journal-title":"Peptides"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.regpep.2009.03.003","article-title":"Ghrelin inhibits apoptosis induced by high glucose and sodium palmitate in adult rat cardiomyocytes through the PI3K-Akt signaling pathway","volume":"155","author":"L Kui","year":"2009","journal-title":"Regul Pept"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.mce.2009.06.006","article-title":"Ghrelin treatment protects lactotrophs from apoptosis in the pituitary of diabetic rats","volume":"309","author":"M Granado","year":"2009","journal-title":"Mol Cell Endocrinol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1210\/en.2006-0266","article-title":"Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic beta-cells and human islets: involvement of 3&apos;,5&apos;-cyclic adenosine monophosphate\/protein kinase A, extracellular signal-regulated kinase 1\/2, and phosphatidyl inositol 3-Kinase\/Akt signaling","volume":"148","author":"R Granata","year":"2007","journal-title":"Endocrinology"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.regpep.2009.12.017","article-title":"Ghrelin inhibits cell apoptosis induced by lipotoxicity in pancreatic beta-cell line","volume":"161","author":"W Wang","year":"2010","journal-title":"Regul Pept"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1210\/me.2003-0459","article-title":"The mitogenic and antiapoptotic actions of ghrelin in 3T3-L1 adipocytes","volume":"18","author":"MS Kim","year":"2004","journal-title":"Mol Endocrinol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.domaniend.2006.11.005","article-title":"Effects of ghrelin and its analogues on chicken ovarian granulosa cells","volume":"34","author":"AV Sirotkin","year":"2008","journal-title":"Domest Anim Endocrinol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0167-0115(03)00117-4","article-title":"Ghrelin, a novel growth hormone-releasing peptide, in the treatment of chronic heart failure","volume":"114","author":"N Nagaya","year":"2003","journal-title":"Regul Pept"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1097\/01.mog.0000245540.87784.75","article-title":"Gastroduodenal mucosal defense","volume":"22","author":"MH Dong","year":"2006","journal-title":"Curr Opin Gastroenterol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.tice.2012.04.009","article-title":"Ghrelin regulates Bax and PCNA but not Bcl-2 expressions following scrotal hyperthermia in the rat","volume":"44","author":"A Kheradmand","year":"2012","journal-title":"Tissue Cell"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s13105-011-0122-2","article-title":"The effect of ghrelin pretreatment on epididymal sperm quality and tissue antioxidant enzyme activities after testicular ischemia\/reperfusion in rats","volume":"68","author":"M Taati","year":"2012","journal-title":"J Physiol Biochem"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/j.1439-0272.2009.00932.x","article-title":"Antioxidant enzyme activity and MDA level in the rat testis following chronic administration of ghrelin","volume":"41","author":"A Kheradmand","year":"2009","journal-title":"Andrologia"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"7973","DOI":"10.1128\/MCB.23.22.7973-7981.2003","article-title":"Deletion of ghrelin impairs neither growth nor appetite","volume":"23","author":"Y Sun","year":"2003","journal-title":"Mol Cell Biol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"4679","DOI":"10.1073\/pnas.0305930101","article-title":"Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor","volume":"101","author":"Y Sun","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1016\/j.fct.2007.01.016","article-title":"Heme oxygenase-1 upregulated by Ginkgo biloba extract: potential protection against ethanol-induced oxidative liver damage","volume":"45","author":"P Yao","year":"2007","journal-title":"Food Chem Toxicol"},{"key":"ref38","first-page":"47","article-title":"A decrease in intracellular glutathione concentration precedes the onset of apoptosis in murine thymocytes","volume":"68","author":"JP Beaver","year":"1995","journal-title":"Eur J Cell Biol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1080\/10715760802317663","article-title":"Glutathione and apoptosis","volume":"42","author":"ML Circu","year":"2008","journal-title":"Free Radic Res"},{"article-title":"Handbook on Genetically Standardized JAX Mice","year":"1991","author":"MC Green","key":"ref40"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1095\/biolreprod.102.006965","article-title":"Cellular location and hormonal regulation of ghrelin expression in rat testis","volume":"67","author":"ML Barreiro","year":"2002","journal-title":"Biol Reprod"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mce.2004.07.015","article-title":"Ghrelin and reproduction: a novel signal linking energy status and fertility?","volume":"226","author":"ML Barreiro","year":"2004","journal-title":"Mol Cell Endocrinol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/1477-7827-3-60","article-title":"Immunohistochemical evidence for an endocrine\/paracrine role for ghrelin in the reproductive tissues of sheep","volume":"3","author":"DW Miller","year":"2005","journal-title":"Reprod Biol Endocrinol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3109\/10520295.2012.724083","article-title":"Effects of capsaicin on testis ghrelin expression in mice","volume":"88","author":"T Ilhan","year":"2013","journal-title":"Biotech Histochem"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1159\/000329983","article-title":"Activation of growth hormone secretagogue type 1a receptor inhibits T-type Ca2+ channel currents through pertussis toxin-sensitive novel protein kinase C pathway in mouse spermatogenic cells","volume":"27","author":"K Liu","year":"2011","journal-title":"Cell Physiol Biochem"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"245","DOI":"10.2220\/biomedres.25.245","article-title":"Ghrelin is expressed in and released from mouse testicular Sertoli TM4 cells","volume":"25","author":"Y. YS Arakawa","year":"2004","journal-title":"Biomed. Res"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/j.1365-2184.1992.tb01399.x","article-title":"Spermatogonial apoptosis has three morphologically recognizable phases and shows no circadian rhythm during normal spermatogenesis in the rat","volume":"25","author":"DJ Allan","year":"1992","journal-title":"Cell Prolif"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1210\/endo.136.1.7828545","article-title":"Apoptosis of male germ cells, a generalized or a cell type-specific phenomenon?","volume":"136","author":"A Bartke","year":"1995","journal-title":"Endocrinology"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1210\/endo.136.1.7828558","article-title":"Apoptosis in testis germ cells: developmental changes in gonadotropin dependence and localization to selective tubule stages","volume":"136","author":"H Billig","year":"1995","journal-title":"Endocrinology"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/S0015-0282(97)00372-5","article-title":"In situ end-labeling of human testicular tissue demonstrates increased apoptosis in conditions of abnormal spermatogenesis","volume":"68","author":"WW Lin","year":"1997","journal-title":"Fertil Steril"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0015-0282(98)00401-4","article-title":"Decreased expression of the c-kit receptor is associated with increased apoptosis in subfertile human testes","volume":"71","author":"HL Feng","year":"1999","journal-title":"Fertil Steril"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1006\/taap.1996.0066","article-title":"Fate of germ cells in 2,5-hexanedione-induced testicular injury. I. Apoptosis is the mechanism of germ cell death","volume":"137","author":"KT Blanchard","year":"1996","journal-title":"Toxicol Appl Pharmacol"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1006\/taap.1996.0055","article-title":"Mono-(2-ethylhexyl) phthalate rapidly alters both Sertoli cell vimentin filaments and germ cell apoptosis in young rat testes","volume":"137","author":"JH Richburg","year":"1996","journal-title":"Toxicol Appl Pharmacol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"32","DOI":"10.3389\/fendo.2013.00032","article-title":"Testicular cancer and cryptorchidism","volume":"4","author":"L Ferguson","year":"2013","journal-title":"Front Endocrinol (Lausanne)"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/978-1-61779-436-0_11","article-title":"Spermatogenesis in cryptorchidism","volume":"825","author":"AI Agoulnik","year":"2012","journal-title":"Methods Mol Biol"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0015-0282(16)43045-1","article-title":"Testicular germ cell differentiation in vivo","volume":"29","author":"Y Nishimune","year":"1978","journal-title":"Fertil Steril"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ydbio.2004.02.018","article-title":"Molecular and genetic regulation of testis descent and external genitalia development","volume":"270","author":"T Klonisch","year":"2004","journal-title":"Dev Biol"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1111\/andr.12070","article-title":"Scrotal ultrasound findings in previously congenital and acquired unilateral undescended testes and their contralateral normally descended testis","volume":"3","author":"J van Brakel","year":"2015","journal-title":"Andrology"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1530\/jrf.0.0140427","article-title":"Development of the rectum\u2014testis temperature difference in the post-natal rat","volume":"14","author":"M Kormano","year":"1967","journal-title":"J Reprod Fertil"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1006\/excr.1996.3447","article-title":"Differential effects of heat shock on translation of normal mRNAs in primary spermatocytes, elongated spermatids, and Sertoli cells in seminiferous tubule culture","volume":"231","author":"L Cataldo","year":"1997","journal-title":"Exp Cell Res"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"325","DOI":"10.2164\/jandrol.108.005934","article-title":"Differential gene expression in the testes of different murine strains under normal and hyperthermic conditions","volume":"30","author":"Y Li","year":"2009","journal-title":"J Androl"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/mrd.20759","article-title":"Scrotal heat stress effects on sperm viability, sperm DNA integrity, and the offspring sex ratio in mice","volume":"75","author":"M Perez-Crespo","year":"2008","journal-title":"Mol Reprod Dev"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1007\/BF02893394","article-title":"Determination of apoptosis through bax expression in cryptorchid testis: an experimental study","volume":"11","author":"M Dundar","year":"2005","journal-title":"Pathol Oncol Res"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1203\/00006450-199608000-00026","article-title":"Apoptotic cell death in the normal and cryptorchid human testis: the effect of human chorionic gonadotropin on testicular cell survival","volume":"40","author":"P Heiskanen","year":"1996","journal-title":"Pediatr Res"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"127","DOI":"10.3109\/01485018708986808","article-title":"Temperature sensitivity of human spermatogonia and spermatocytes in vitro","volume":"19","author":"M Nakamura","year":"1987","journal-title":"Arch Androl"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1095\/biolreprod58.2.492","article-title":"Experimental cryptorchidism induces testicular germ cell apoptosis by p53-dependent and -independent pathways in mice","volume":"58","author":"Y Yin","year":"1998","journal-title":"Biol Reprod"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1016\/S0002-9440(10)63614-0","article-title":"Expression of a K48R mutant ubiquitin protects mouse testis from cryptorchid injury and aging","volume":"163","author":"RJ Rasoulpour","year":"2003","journal-title":"Am J Pathol"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.jpedsurg.2013.10.003","article-title":"Ghrelin is a suppressor of testicular damage following experimentally induced cryptorchidism in the rat","volume":"49","author":"A Kheradmand","year":"2014","journal-title":"J Pediatr Surg"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0177995","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T10:30:26Z","timestamp":1719225026000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0177995"}},"subtitle":[],"editor":[{"given":"Jean-Pierre","family":"Rouault","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2017,5,18]]},"references-count":68,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2017,5,18]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0177995","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2017,5,18]]}}}