{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:03:20Z","timestamp":1792785800926,"version":"4.5.0"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T00:00:00Z","timestamp":1615420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Major Project of Breeding New Varieties of Transgenic Organisms","award":["2016ZX080803"],"award-info":[{"award-number":["2016ZX080803"]}]},{"name":"Major Project of Breeding New Varieties of Transgenic Organisms","award":["2018ZX0800801B"],"award-info":[{"award-number":["2018ZX0800801B"]}]},{"name":"National Creature Breeding Grand Project","award":["2018ZX08008-01B"],"award-info":[{"award-number":["2018ZX08008-01B"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31830091"],"award-info":[{"award-number":["31830091"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Beijing Dairy Industry Innovation Team","award":["BAIC06-2017"],"award-info":[{"award-number":["BAIC06-2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Leydig cells play a critical role in male reproductive physiology, and their dysfunction is usually associated with male infertility. Melatonin has an important protective and regulatory role in these cells. However, the lack of suitable animal models impedes us from addressing the impact of endogenous melatonin on these cells. In the current study, by using arylalkylamine N-acetyltransferase (AANAT) overexpression transgenic sheep and AANAT knockout mice, we confirmed the regulatory effects of endogenously occurring melatonin on Leydig cells as well as its beneficial effects on male reproductive performance. The results showed that the endogenously elevated melatonin level was correlated with decreased Leydig cell apoptosis, increased testosterone production, and improved quality of sperm in melatonin-enriched transgenic mammals. Signal transduction analysis indicated that melatonin targeted the mitochondrial apoptotic Bax\/Bcl2 pathway and thus suppressed Leydig cell apoptosis. In addition, melatonin upregulated the expression of testosterone synthesis-related genes of Steroidogenic Acute Regulatory Protein (StAR), Steroidogenic factor 1 (SF1), and Transcription factor GATA-4 (Gata4) in Leydig cells. This action was primarily mediated by the melatonin nuclear receptor RAR-related orphan receptor alpha (ROR\u03b1) since blockade of this receptor suppressed the effect of melatonin on testosterone synthesis. All of these actions of melatonin cause Leydig cells to generate more testosterone, which is necessary for spermatogenesis in mammals. In contrast, AANAT knockout animals have dysfunctional Leydig cells and reduced reproductive performance.<\/jats:p>","DOI":"10.1093\/biolre\/ioab046","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T23:39:54Z","timestamp":1615505994000},"page":"1322-1336","source":"Crossref","is-referenced-by-count":70,"title":["Melatonin promotes male reproductive performance and increases testosterone synthesis in mammalian Leydig cells"],"prefix":"10.1093","volume":"104","author":[{"given":"Minghui","family":"Yang","sequence":"first","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengyu","family":"Guan","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingli","family":"Tao","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China"},{"name":"College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuanfeng","family":"Zhu","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongying","family":"Lv","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangdong","family":"Li","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuefeng","family":"Gao","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghao","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Cao","sequence":"additional","affiliation":[{"name":"Beijing Institute of Feed Control, Beijing Municipal Bureau of Agriculture and Rural Affairs, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Fu","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengyun","family":"Ji","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengxing","family":"Lian","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoshi","family":"Liu","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,3,11]]},"reference":[{"key":"2021060706375711000_ref1","doi-asserted-by":"crossref","first-page":"116","DOI":"10.4161\/spmg.1.2.16956","article-title":"Testosterone signaling and the regulation of spermatogenesis","volume":"1","author":"Walker","year":"2011","journal-title":"Spermatogenesis"},{"key":"2021060706375711000_ref2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.semcdb.2014.02.012","article-title":"The regulation of spermatogenesis by androgens","volume":"30","author":"Smith","year":"2014","journal-title":"Semin Cell Dev Biol"},{"key":"2021060706375711000_ref3","first-page":"1287","article-title":"The impact of exogenous testosterone supplementation on spermatogenesis in a rat model of oligoasthenospermia","volume":"13","author":"An","year":"2020","journal-title":"Int J Clin Exp Pathol"},{"key":"2021060706375711000_ref4","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/B978-0-12-803678-5.00265-4","volume-title":"International Encyclopedia of Public Health","author":"Behre","year":"2017","edition":"Second"},{"key":"2021060706375711000_ref5","doi-asserted-by":"crossref","first-page":"10373","DOI":"10.1096\/fj.202000361R","article-title":"Ablation of the canonical testosterone production pathway via knockout of the steroidogenic enzyme HSD17B3, reveals a novel mechanism of testicular testosterone production","volume":"34","author":"Rebourcet","year":"2020","journal-title":"FASEB J"},{"key":"2021060706375711000_ref6","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1002\/jcp.25700","article-title":"Interactive effect of corticosterone and lactate on regulation of testosterone production in rat Leydig cells","volume":"232","author":"Chen","year":"2017","journal-title":"J Cell Physiol"},{"key":"2021060706375711000_ref7","doi-asserted-by":"crossref","first-page":"184","DOI":"10.3109\/13685538.2013.839648","article-title":"Effects of testosterone treatment on body composition in males with testosterone deficiency syndrome","volume":"16","author":"Rodriguez-Tolra","year":"2013","journal-title":"Aging Male"},{"key":"2021060706375711000_ref8","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1111\/jsm.12393","article-title":"Prevalence of symptoms and associated comorbidities of testosterone deficiency syndrome in the Korean general population","volume":"11","author":"Moon","year":"2014","journal-title":"J Sex Med"},{"key":"2021060706375711000_ref9","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.eursup.2007.07.001","article-title":"Testosterone deficiency syndrome in males: Science and politics","volume":"6","author":"Morales","year":"2007","journal-title":"Eur Urol Suppl"},{"key":"2021060706375711000_ref10","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/jpi.12010","article-title":"On the free radical scavenging activities of melatonin's metabolites, AFMK and AMK","volume":"54","author":"Galano","year":"2013","journal-title":"J Pineal Res"},{"key":"2021060706375711000_ref11","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/0024-3205(94)00928-7","article-title":"Potent protective effect of melatonin on in vivo paraquat-induced oxidative damage in rats","volume":"56","author":"Melchiorri","year":"1994","journal-title":"Life Sci"},{"key":"2021060706375711000_ref12","doi-asserted-by":"crossref","first-page":"181","DOI":"10.2174\/1568026023394443","article-title":"Chemical and physical properties and potential mechanisms: Melatonin as a broad spectrum antioxidant and free radical scavenger","volume":"2","author":"Tan","year":"2002","journal-title":"Curr Top Med Chem"},{"key":"2021060706375711000_ref13","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1111\/jpi.12267","article-title":"Melatonin: An ancient molecule that makes oxygen metabolically tolerable","volume":"59","author":"Manchester","year":"2015","journal-title":"J Pineal Res"},{"key":"2021060706375711000_ref14","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1080\/15287390801988020","article-title":"Arylalkylamine N-acetyltransferase (AANAT) genotype as a personal trait in melatonin synthesis","volume":"71","author":"Bl\u00f6meke","year":"2008","journal-title":"J Toxicol Environ Health Part A"},{"key":"2021060706375711000_ref15","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/S1074-5521(01)00020-5","article-title":"Mechanistic studies on the alkyltransferase activity of serotonin N-acetyltransferase","volume":"8","author":"Zheng","year":"2001","journal-title":"Chem Biol"},{"key":"2021060706375711000_ref16","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/j.1600-079X.2009.00673.x","article-title":"Cloning and characterization of a Chlamydomonas reinhardtii cDNA arylalkylamine N-acetyltransferase and its use in the genetic engineering of melatonin content in the Micro-Tom tomato","volume":"46","author":"Okazaki","year":"2009","journal-title":"J Pineal Res"},{"key":"2021060706375711000_ref17","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12406","article-title":"An AANAT\/ASMT transgenic animal model constructed with CRISPR\/Cas9 system serving as the mammary gland bioreactor to produce melatonin-enriched milk in sheep","volume":"63","author":"Ma","year":"2017","journal-title":"J Pineal Res"},{"key":"2021060706375711000_ref18","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1080\/15548627.2018.1490852","article-title":"Effects of AANAT overexpression on the inflammatory responses and autophagy activity in the cellular and transgenic animal levels","volume":"14","author":"Tao","year":"2018","journal-title":"Autophagy"},{"key":"2021060706375711000_ref19","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/jpi.12162","article-title":"Melatonin: A well-documented antioxidant with conditional pro-oxidant actions","volume":"57","author":"Zhang","year":"2014","journal-title":"J Pineal Res"},{"key":"2021060706375711000_ref20","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/j.1600-079X.2011.00921.x","article-title":"Xu DX. Melatonin alleviates cadmium-induced cellular stress and germ cell apoptosis in testes","volume":"52","author":"Ji","year":"2012","journal-title":"J Pineal Res"},{"key":"2021060706375711000_ref21","first-page":"639","article-title":"Melatonin ameliorates testicular damages induced by nicotine in mice","volume":"21","author":"Mohammadghasemi","year":"2018","journal-title":"Iran J Basic Med Sci"},{"key":"2021060706375711000_ref22","doi-asserted-by":"crossref","DOI":"10.5812\/ircmj.14463","article-title":"Melatonin and testicular damage in busulfan treated mice","volume":"16","author":"Mirhoseini","year":"2014","journal-title":"Iran Red Crescent Med J"},{"key":"2021060706375711000_ref23","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.cca.2015.04.029","article-title":"Melatonin and male reproduction","volume":"446","author":"Li","year":"2015","journal-title":"Clin Chim Acta"},{"key":"2021060706375711000_ref24","doi-asserted-by":"crossref","DOI":"10.1111\/and.13323","article-title":"Melatonin appears to protect against steroidogenic collapse in both mice fed with high-fat diet and H2O2-treated TM3 cells","volume":"51","author":"Chen","year":"2019","journal-title":"Andrologia"},{"key":"2021060706375711000_ref25","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.theriogenology.2017.10.025","article-title":"Melatonin promotes sheep Leydig cell testosterone secretion in a co-culture with Sertoli cells","volume":"106","author":"Deng","year":"2018","journal-title":"Theriogenology"},{"key":"2021060706375711000_ref26","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1071\/RD14165","article-title":"Decreased melatonin levels and increased levels of advanced oxidation protein products in the seminal plasma are related to male infertility","volume":"28","author":"Kratz","year":"2016","journal-title":"Reprod Fertil Dev"},{"key":"2021060706375711000_ref27","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0093-691X(98)00136-8","article-title":"Circadian and pulsatile variations in plasma levels of inhibin, FSH, LH and testosterone in adult Murrah buffalo bulls","volume":"50","author":"Dixit","year":"1998","journal-title":"Theriogenology"},{"key":"2021060706375711000_ref28","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/j.1365-2265.1983.tb00019.x","article-title":"Circannual rhythms of plasma luteinizing hormone, follicle-stimulating hormone, testosterone, prolactin and cortisol in prepuberty","volume":"19","author":"Bellastella","year":"1983","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2021060706375711000_ref29","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0079-6123(08)62942-8","article-title":"Effects of melatonin administration on the reproductive system of the male rat","volume":"52","author":"Mas","year":"1979","journal-title":"Prog Brain Res"},{"key":"2021060706375711000_ref30","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1159\/000122616","article-title":"Melatonin inhibition of reproduction in the male hamster: Its dependency on time of day of administration and on an intact and sympathetically innervated pineal gland","volume":"22","author":"Reiter","year":"1976","journal-title":"Neuroendocrinology"},{"key":"2021060706375711000_ref31","first-page":"763","article-title":"Persistence of fertility despite semen alterations in a pinealectomised patient treated with melatonin","volume":"34","author":"Kocher","year":"2013","journal-title":"Neuro Endocrinol Lett"},{"key":"2021060706375711000_ref32","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.theriogenology.2015.05.032","article-title":"Effect of different media additives on capacitation of frozen\u2013thawed ram spermatozoa as a potential replacement for estrous sheep serum","volume":"84","author":"Garc\u00eda-\u00c1lvarez","year":"2015","journal-title":"Theriogenology"},{"key":"2021060706375711000_ref33","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1071\/RD13034","article-title":"Dynamics of sperm subpopulations based on motility and plasma membrane status in thawed ram spermatozoa incubated under conditions that support in vitro capacitation and fertilisation","volume":"26","author":"Garc\u00eda-\u00c1lvarez","year":"2014","journal-title":"Reprod Fertil Dev"},{"key":"2021060706375711000_ref34","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1071\/RD99019","article-title":"Kinematic definition of ram sperm hyperactivation","volume":"11","author":"Mortimer","year":"1999","journal-title":"Reprod Fertil Dev"},{"key":"2021060706375711000_ref35","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/j.1939-4640.1990.tb03228.x","article-title":"Kinematics of human spermatozoa incubated under capacitating conditions","volume":"11","author":"Mortimer","year":"1990","journal-title":"J Androl"},{"key":"2021060706375711000_ref36","first-page":"157","article-title":"Melatonin as a new possible anti-inflammatory agent","volume":"11","author":"Lissoni","year":"1997","journal-title":"J Biol Regul Homeost Agents"},{"key":"2021060706375711000_ref37","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3109\/10715762.2013.845295","article-title":"Melatonin suppresses nitric oxide production in glial cultures by pro-inflammatory cytokines through p38 MAPK inhibition","volume":"48","author":"Vilar","year":"2014","journal-title":"Free Radic Res"},{"key":"2021060706375711000_ref38","doi-asserted-by":"crossref","first-page":"8638","DOI":"10.3390\/ijms14048638","article-title":"Melatonin: Buffering the immune system","volume":"14","author":"Carrillo-Vico","year":"2013","journal-title":"Int J Mol Sci"},{"key":"2021060706375711000_ref39","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/0024-3205(94)00417-Q","article-title":"Potent protective effect of melatonin on in vivo paraquat-induced oxidative damage in rats","volume":"56","author":"Melchiorri","year":"1995","journal-title":"Life Sci"},{"key":"2021060706375711000_ref40","doi-asserted-by":"crossref","first-page":"12107","DOI":"10.3390\/ijms150712107","article-title":"Melatonin promotes superovulation in sika deer (Cervus nippon)","volume":"15","author":"Wang","year":"2014","journal-title":"Int J Mol Sci"},{"key":"2021060706375711000_ref41","doi-asserted-by":"crossref","first-page":"939","DOI":"10.3390\/ijms17060939","article-title":"Mitochondria synthesize Melatonin to ameliorate its function and improve mice Oocyte's quality under in vitro conditions","volume":"17","author":"He","year":"2016","journal-title":"Int J Mol Sci"},{"key":"2021060706375711000_ref42","doi-asserted-by":"crossref","first-page":"3422","DOI":"10.3390\/ijms19113422","article-title":"Melatonin improves oocyte maturation and mitochondrial functions by reducing bisphenol A-derived superoxide in porcine oocytes in vitro","volume":"19","author":"Park","year":"2018","journal-title":"Int J Mol Sci"},{"key":"2021060706375711000_ref43","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s40104-016-0093-9","article-title":"Resveratrol compares with melatonin in improving in vitro porcine oocyte maturation under heat stress","volume":"7","author":"Li","year":"2016","journal-title":"J Anim Sci Biotechnol"},{"key":"2021060706375711000_ref44","first-page":"598","article-title":"Melatonin improves the fertilization ability of post-ovulatory aged mouse oocytes by stabilizing ovastacin and Juno to promote sperm binding and fusion","volume":"32","author":"Dai","year":"2017","journal-title":"Hum Reprod"},{"key":"2021060706375711000_ref45","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12445","article-title":"Melatonin improves the fertilization capacity and developmental ability of bovine oocytes by regulating cytoplasmic maturation events","volume":"64","author":"Zhao","year":"2018","journal-title":"J Pineal Res"},{"key":"2021060706375711000_ref46","first-page":"21","article-title":"The effect of Melatonin on semen quality and subsequent embryonic development in male mice after heat stress","volume":"50","author":"Xu","year":"2014","journal-title":"Chin J Anim Sci"},{"key":"2021060706375711000_ref47","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.freeradbiomed.2019.04.009","article-title":"Melatonin protects spermatogonia from the stress of chemotherapy and oxidation via eliminating reactive oxidative species","volume":"137","author":"Zhang","year":"2019","journal-title":"Free Radic Biol Med"},{"key":"2021060706375711000_ref48","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/j.1939-4640.2004.tb02778.x","article-title":"Melatonin administration alters semen quality in normal men","volume":"25","author":"Lerchl","year":"2004","journal-title":"J Androl"},{"key":"2021060706375711000_ref49","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1111\/and.12308","article-title":"Supplementation of IVF medium with melatonin: Effect on sperm functionality and in vitro produced bovine embryos","volume":"47","author":"Cheuqueman","year":"2015","journal-title":"Andrologia"},{"key":"2021060706375711000_ref50","first-page":"38","article-title":"Effect of pinealectomy on reproductive functions of male rats","volume":"2009","author":"Tian","year":"2009","journal-title":"Chongqing Medicine"},{"key":"2021060706375711000_ref51","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1002\/aja.1001670408","article-title":"Effects of pinealectomy on reproduction in the Syrian hamster mutant anophthalmic white (Wh)","volume":"167","author":"Hagen","year":"1983","journal-title":"Am J Anat"},{"key":"2021060706375711000_ref52","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.tem.2007.10.007","article-title":"Melatonin in the skin: Synthesis, metabolism and functions","volume":"19","author":"Slominski","year":"2008","journal-title":"Trends Endocrinol Metab"},{"key":"2021060706375711000_ref53","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0197-0186(95)00037-9","article-title":"Melatonin synthesis in the retina and pineal gland of Djungarian hamsters at different times of the year","volume":"27","author":"Steinlechner","year":"1995","journal-title":"Neurochem Int"},{"key":"2021060706375711000_ref54","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s00360-016-0966-4","article-title":"Characterization of melatonin synthesis in the gastrointestinal tract of rainbow trout (Oncorhynchus mykiss): Distribution, relation with serotonin, daily rhythms and photoperiod regulation","volume":"186","author":"Munoz-Perez","year":"2016","journal-title":"J Comp Physiol B"},{"key":"2021060706375711000_ref55","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/j.1749-6632.1994.tb56826.x","article-title":"Melatonin synthesis in the gastrointestinal tract and the impact of nutritional factors on circulating melatonin","volume":"719","author":"Huether","year":"1994","journal-title":"Ann N Y Acad Sci"},{"key":"2021060706375711000_ref56","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1089\/ars.2018.7555","article-title":"Melatonin supplementation in embryo development: Involvement of mitochondrial function and DNA methylation","volume":"30","author":"Yang","year":"2019","journal-title":"Antioxid Redox Signal"},{"key":"2021060706375711000_ref57","doi-asserted-by":"crossref","first-page":"110592","DOI":"10.18632\/oncotarget.22855","article-title":"Melatonin up-regulates the expression of the GATA-4 transcription factor and increases testosterone secretion from Leydig cells through RORalpha signaling in an in vitro goat spermatogonial stem cell differentiation culture system","volume":"8","author":"Deng","year":"2017","journal-title":"Oncotarget"},{"key":"2021060706375711000_ref58","article-title":"Melatonergic systems of AANAT, melatonin, and its receptor MT2 in the corpus luteum are essential for reproductive success in mammals","author":"Wang","year":"2020","journal-title":"Biol Reprod"},{"key":"2021060706375711000_ref59","first-page":"553","article-title":"Effects of nickel sulfate on cell proliferation and testosterone synthesis in mice testicular Leydig cells","volume":"45","author":"Biyong","year":"2018","journal-title":"China Occup Med"},{"key":"2021060706375711000_ref60","first-page":"12","article-title":"ZnT8 is involved in testosterone synthesis in mouse Leydig cells","volume":"18","author":"Zhong","year":"2012","journal-title":"Prog Anat Sci"},{"key":"2021060706375711000_ref61","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/nrurol.2017.69","article-title":"Oxidative stress and male infertility","volume":"14","author":"Bisht","year":"2017","journal-title":"Nat Rev Urol"},{"key":"2021060706375711000_ref62","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1093\/humrep\/der132","article-title":"The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy","volume":"26","author":"Gharagozloo","year":"2011","journal-title":"Hum Reprod"},{"key":"2021060706375711000_ref63","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.3390\/molecules24173084","article-title":"Apoptosis and oxidative stress of mouse Leydig cells via a SIRT1-dependent mechanism","volume":"24","author":"Xu","year":"2019","journal-title":"Molecules"}],"container-title":["Biology of Reproduction"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/biolreprod\/advance-article-pdf\/doi\/10.1093\/biolre\/ioab046\/36875412\/ioab046.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/biolreprod\/article-pdf\/104\/6\/1322\/38488224\/ioab046.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/biolreprod\/article-pdf\/104\/6\/1322\/38488224\/ioab046.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,22]],"date-time":"2023-10-22T20:10:31Z","timestamp":1698005431000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biolreprod\/article\/104\/6\/1322\/6168287"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,11]]},"references-count":63,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,3,11]]},"published-print":{"date-parts":[[2021,6,4]]}},"URL":"https:\/\/doi.org\/10.1093\/biolre\/ioab046","relation":{},"ISSN":["0006-3363","1529-7268"],"issn-type":[{"value":"0006-3363","type":"print"},{"value":"1529-7268","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,6]]},"published":{"date-parts":[[2021,3,11]]}}}