{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:45:36Z","timestamp":1791272736891,"version":"4.1.0"},"reference-count":78,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,2,8]],"date-time":"2020-02-08T00:00:00Z","timestamp":1581120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Melatonin is probably produced in all cells but is only secreted by the pineal gland. The pineal secretion of melatonin is determined by the light\u2013dark cycle, and it is only released at night. Melatonin regulates biological rhythms via its receptors located in the suprachiasmatic nuclei of the hypothalamus. Melatonin also has strong antioxidant activities to scavenge free radicals such as reactive oxygen species (ROS). The direct free radical scavenging actions are receptor independent. ROS play an important role in reproductive function including in the ovulatory process. However, excessive ROS can also have an adverse effect on oocytes because of oxidative stress, thereby causing infertility. It is becoming clear that melatonin is located in the ovarian follicular fluid and in the oocytes themselves, which protects these cells from oxidative damage as well as having other beneficial actions in oocyte maturation, fertilization, and embryo development. Trials on humans have investigated the improvement of outcomes of assisted reproductive technology (ART), such as in vitro fertilization and embryo transfer (IVF-ET), by way of administering melatonin to patients suffering from infertility. In addition, clinical research has examined melatonin as an anti-aging molecule via its antioxidative actions, and its relationship with the aging diseases, e.g., Alzheimer\u2019s and Parkinson\u2019s disease, is also underway. Melatonin may also reduce ovarian aging, which is a major issue in assisted reproductive technology. This review explains the relationship between melatonin and human reproductive function, as well as the clinical applications expected to improve the outcomes of assisted reproductive technology such as IVF, while also discussing possibilities for melatonin in preventing ovarian aging.<\/jats:p>","DOI":"10.3390\/ijms21031135","type":"journal-article","created":{"date-parts":[[2020,2,10]],"date-time":"2020-02-10T11:48:51Z","timestamp":1581335331000},"page":"1135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":209,"title":["Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging"],"prefix":"10.3390","volume":"21","author":[{"given":"Hiroshi","family":"Tamura","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Jozaki","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Tanabe","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Saiseikai Shimonoseki General Hospital, Yasuokacho 8-5-1, Shimonoseki 759-6603, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Shirafuta","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumiko","family":"Mihara","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Shinagawa","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isao","family":"Tamura","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0923-376X","authenticated-orcid":false,"given":"Ryo","family":"Maekawa","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Taketani","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihisa","family":"Takasaki","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Saiseikai Shimonoseki General Hospital, Yasuokacho 8-5-1, Shimonoseki 759-6603, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russel J.","family":"Reiter","sequence":"additional","affiliation":[{"name":"Department of Cellular and Structural Biology, The University of Texas Health Science Center, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihiro","family":"Sugino","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.3389\/fendo.2019.00249","article-title":"Melatonin synthesis and function: Evolutionary history in animals and plants","volume":"10","author":"Zhao","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_2","first-page":"325","article-title":"Melatonin: Exceeding expectations","volume":"29","author":"Reiter","year":"2014","journal-title":"Physiology (Bethesda)"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1007\/s00018-014-1579-2","article-title":"Extrapineal melatonin: Sources, regulation, and potential functions","volume":"71","author":"Escames","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.arr.2018.07.010","article-title":"The role of melatonin, a multitasking molecule, in retarding the processes of ageing","volume":"47","author":"Majidinia","year":"2018","journal-title":"Ageing Res. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1002\/rmb2.12089","article-title":"Modulation of bone morphogenetic protein activity by melatonin in ovarian steroidogenesis","volume":"17","author":"Otsuka","year":"2018","journal-title":"Reprod. Med. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/j.1600-079X.2008.00561.x","article-title":"Melatonin treatment in peri- and postmenopausal women elevates serum high-density lipoprotein cholesterol levels without influencing total cholesterol levels","volume":"45","author":"Tamura","year":"2008","journal-title":"J. Pineal Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/j.1600-079X.1998.tb00551.x","article-title":"Melatonin directly suppresses steroid production by preovulatory follicles in the cyclic hamster","volume":"25","author":"Tamura","year":"1998","journal-title":"J. Pineal Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.lfs.2015.12.031","article-title":"Melatonin, bone regulation and the ubiquitin-proteasome connection: A review","volume":"145","author":"Vriend","year":"2016","journal-title":"Life Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cytogfr.2019.07.002","article-title":"Potential role of melatonin in autoimmune diseases","volume":"48","author":"Zhao","year":"2019","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.3389\/fphar.2018.01086","article-title":"Promising antineoplastic actions of melatonin","volume":"9","author":"Favero","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Reiter, R.J., Rosales-Corral, S.A., Tan, D.X., Acuna-Castroviejo, D., Qin, L., Yang, S.F., and Xu, K. (2017). Melatonin, a full service anti-cancer agent: Inhibition of initiation, progression and metastasis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18040843"},{"key":"ref_12","first-page":"3851","article-title":"Clinical uses of melatonin in neurological diseases and mental and behavioural disorders","volume":"24","author":"Rueda","year":"2017","journal-title":"Curr. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/jpi.12137","article-title":"Melatonin, energy metabolism, and obesity: A review","volume":"56","author":"Amaral","year":"2014","journal-title":"J. Pineal Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Favero, G., Franceschetti, L., Bonomini, F., Rodella, L.F., and Rezzani, R. (2017). Melatonin as an anti-inflammatory agent modulating inflammasome activation. Int. J. Endocrinol., 1835195.","DOI":"10.1155\/2017\/1835195"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ma, N., Zhang, J., Reiter, R.J., and Ma, X. (2019). Melatonin mediates mucosal immune cells, microbial metabolism, and rhythm crosstalk: A therapeutic target to reduce intestinal inflammation. Med. Res. Rev.","DOI":"10.1002\/med.21628"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1002\/jcp.29036","article-title":"Immunoregulatory role of melatonin in cancer","volume":"235","author":"Moradkhani","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1002\/jnr.24220","article-title":"The neuroprotective role of melatonin in neurological disorders","volume":"96","author":"Alghamdi","year":"2018","journal-title":"J. Neurosci. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"480","DOI":"10.3389\/fendo.2019.00480","article-title":"Melatonin: Clinical perspectives in neurodegeneration","volume":"10","author":"Cardinali","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/s41574-018-0130-1","article-title":"Melatonin in type 2 diabetes mellitus and obesity","volume":"15","author":"Karamitri","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9740568","DOI":"10.1155\/2019\/9740568","article-title":"Therapeutic opportunities in colorectal cancer: Focus on melatonin antioncogenic action","volume":"2019","author":"Wu","year":"2019","journal-title":"BioMed Res. Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/164_2018_139","article-title":"Advances of melatonin-based therapies in the treatment of disturbed sleep and mood","volume":"253","author":"Alston","year":"2019","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Reiter, R.J., Tan, D.X., Rosales-Corral, S., Galano, A., Zhou, X.J., and Xu, B. (2018). Mitochondria: Central organelles for melatonin\u2019s antioxidant and anti-aging actions. Molecules, 23.","DOI":"10.3390\/molecules23020509"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S0149-7634(05)80016-8","article-title":"The significance of the metabolism of the neurohormone melatonin: Antioxidative protection and formation of bioactive substances","volume":"17","author":"Hardeland","year":"1993","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/j.1600-079X.1993.tb00498.x","article-title":"Melatonin, hydroxyl radical-mediated oxidative damage, and aging: A hypothesis","volume":"14","author":"Poeggeler","year":"1993","journal-title":"J. Pineal Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1006\/frne.1995.1014","article-title":"Functional pleiotropy of the neurohormone melatonin: Antioxidant protection and neuroendocrine regulation","volume":"16","author":"Reiter","year":"1995","journal-title":"Front. Neuroendocrinol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"21","DOI":"10.32794\/mr11250002","article-title":"Melatonin actions in the heart; more than a hormone","volume":"1","author":"Reiter","year":"2018","journal-title":"Melatonin Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-079X.2004.00181.x","article-title":"Melatonin mitigates mitochondrial malfunction","volume":"38","author":"Leon","year":"2005","journal-title":"J. Pineal Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1111\/j.1600-079X.2010.00759.x","article-title":"Melatonin, cardiolipin and mitochondrial bioenergetics in health and disease","volume":"48","author":"Paradies","year":"2010","journal-title":"J. Pineal Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1080\/10409230903044914","article-title":"Reducing oxidative\/nitrosative stress: A newly-discovered genre for melatonin","volume":"44","author":"Reiter","year":"2009","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/j.1600-079X.2011.00931.x","article-title":"Extrapineal melatonin: Analysis of its subcellular distribution and daily fluctuations","volume":"52","author":"Venegas","year":"2012","journal-title":"J. Pineal Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1600-079X.2003.00092.x","article-title":"Regulation of antioxidant enzymes: A significant role for melatonin","volume":"36","author":"Rodriguez","year":"2004","journal-title":"J. Pineal Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"44","DOI":"10.32794\/mr11250011","article-title":"Mitochondria: The birth place, battle ground and the site of melatonin metabolism in cells","volume":"2","author":"Tan","year":"2019","journal-title":"Melatonin Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/978-1-4615-0135-0_62","article-title":"Melatonin: Detoxification of oxygen and nitrogen-based toxic reactants","volume":"527","author":"Reiter","year":"2003","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1600-079X.2006.00407.x","article-title":"One molecule, many derivatives: A never-ending interaction of melatonin with reactive oxygen and nitrogen species?","volume":"42","author":"Tan","year":"2007","journal-title":"J. Pineal Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s40659-018-0168-5","article-title":"and Chakraborty, S.B. Melatonin ameliorates H2O2-induced oxidative stress through modulation of Erk\/Akt\/NFkB pathway","volume":"51","author":"Moniruzzaman","year":"2018","journal-title":"Biol. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/rmb2.12013","article-title":"Equilibrium between anti-oxidants and reactive oxygen species: A requisite for oocyte development and maturation","volume":"16","author":"Kala","year":"2017","journal-title":"Reprod. Med. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"He, C., Wang, J., Zhang, Z., Yang, M., Li, Y., Tian, X., Ma, T., Tao, J., Zhu, K., and Song, Y. (2016). Mitochondria synthesize melatonin to ameliorate its function and improve mice oocyte\u2019s quality under in vitro conditions. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060939"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1757-2215-5-5","article-title":"The role of melatonin as an antioxidant in the follicle","volume":"5","author":"Tamura","year":"2012","journal-title":"J. Ovarian. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1111\/j.1600-079X.2007.00524.x","article-title":"Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilization rate","volume":"44","author":"Tamura","year":"2008","journal-title":"J. Pineal Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.theriogenology.2014.07.011","article-title":"Essential actions of melatonin in protecting the ovary from oxidative damage","volume":"82","author":"Cruz","year":"2014","journal-title":"Theriogenology"},{"key":"ref_41","first-page":"314","article-title":"The uptake of H3-melatonin in endocrine and nervous tissues and the effects of constant light exposure","volume":"143","author":"Wurtman","year":"1964","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/S0015-0282(03)01008-2","article-title":"Increased endogenous level of melatonin in preovulatory human follicles does not directly influence progesterone production","volume":"80","author":"Nakamura","year":"2003","journal-title":"Fertil. Steril."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1262\/jrd.2014-105","article-title":"Melatonin protects the integrity of granulosa cells by reducing oxidative stress in nuclei, mitochondria, and plasma membranes in mice","volume":"61","author":"Tanabe","year":"2015","journal-title":"J. Reprod. Dev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"R103","DOI":"10.1530\/REP-14-0242","article-title":"Oocyte ageing and epigenetics","volume":"149","author":"Ge","year":"2015","journal-title":"Reproduction"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s00441-015-2264-y","article-title":"Targeting oocyte maturation to improve fertility in older women","volume":"363","author":"Liu","year":"2015","journal-title":"Cell Tissue Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3109\/09513590.2011.589925","article-title":"The efficacy of melatonin administration on oocyte quality","volume":"28","author":"Batioglu","year":"2012","journal-title":"Gynecol. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s10815-011-9604-y","article-title":"Melatonin improves the oocyte and the embryo in IVF patients with sleep disturbances, but does not improve the sleeping problems","volume":"28","author":"Eryilmaz","year":"2011","journal-title":"J. Assist. Reprod Genet."},{"key":"ref_48","first-page":"73","article-title":"Effect of melatonin on the outcome of assisted reproductive technique cycles in women with diminished ovarian reserve: A double-blinded randomized clinical trial","volume":"42","author":"Jahromi","year":"2017","journal-title":"Iran. J. Med. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3109\/09513590.2013.879856","article-title":"Oral melatonin supplementation improves oocyte and embryo quality in women undergoing in vitro fertilization-embryo transfer","volume":"30","author":"Nishihara","year":"2014","journal-title":"Gynecol. Endocrinol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Espino, J., Macedo, M., Lozano, G., Ortiz, A., Rodriguez, C., Rodriguez, A.B., and Bejarano, I. (2019). Impact of melatonin supplementation in women with unexplained infertility undergoing fertility treatment. Antioxidants, 8.","DOI":"10.3390\/antiox8090338"},{"key":"ref_51","first-page":"244","article-title":"Melatonin modifies histone acetylation during in vitro maturation of mouse oocytes","volume":"20","author":"Keshavarzi","year":"2018","journal-title":"Cell. J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1002\/mrd.23052","article-title":"Melatonin supplementation during prolonged in vitro maturation improves the quality and development of poor-quality porcine oocytes via anti-oxidative and anti-apoptotic effects","volume":"85","author":"Lin","year":"2018","journal-title":"Mol. Reprod Dev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1111\/rda.13097","article-title":"Melatonin reduces apoptotic cells, SOD2 and HSPB1 and improves the in vitro production and quality of bovine blastocysts","volume":"53","author":"Marques","year":"2018","journal-title":"Reprod. Domest. Anim."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e12543","DOI":"10.1111\/jpi.12543","article-title":"Melatonin protects in vitro matured porcine oocytes from toxicity of Aflatoxin B1","volume":"66","author":"Cheng","year":"2019","journal-title":"J. Pineal Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Park, H.J., Park, S.Y., Kim, J.W., Yang, S.G., Kim, M.J., Jegal, H.G., Kim, I.S., Choo, Y.K., and Koo, D.B. (2018). Melatonin improves oocyte maturation and mitochondrial functions by reducing bisphenol A-derived superoxide in porcine oocytes in vitro. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113422"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"17370","DOI":"10.1002\/jcp.28357","article-title":"Melatonin supplementation during in vitro maturation of oocyte enhances subsequent development of bovine cloned embryos","volume":"234","author":"An","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e12424","DOI":"10.1111\/jpi.12424","article-title":"Melatonin influences the sonic hedgehog signaling pathway in porcine cumulus oocyte complexes","volume":"63","author":"Lee","year":"2017","journal-title":"J. Pineal Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1111\/asj.12970","article-title":"Protective effects of melatonin on the in vitro developmental competence of bovine oocytes","volume":"89","author":"Pang","year":"2018","journal-title":"Anim. Sci. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.freeradbiomed.2018.11.027","article-title":"Melatonin-induced demethylation of antioxidant genes increases antioxidant capacity through RORalpha in cumulus cells of prepubertal lambs","volume":"131","author":"Fang","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Fang, Y., Deng, S., Zhang, J., Liu, H., Li, Y., Zhang, X., and Liu, Y. (2018). Melatonin-mediated development of ovine cumulus cells, perhaps by regulation of DNA methylation. Molecules, 23.","DOI":"10.3390\/molecules23020494"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"791","DOI":"10.3389\/fendo.2019.00791","article-title":"Melatonin target proteins: Too many or not enough?","volume":"10","author":"Liu","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Lee, S., Jin, J.X., Taweechaipaisankul, A., Kim, G.A., and Lee, B.C. (2018). Stimulatory effects of melatonin on porcine in vitro maturation are mediated by MT2 receptor. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061581"},{"key":"ref_63","first-page":"157","article-title":"Melatonin improves the developmental competence of goat oocytes","volume":"12","author":"Saeedabadi","year":"2018","journal-title":"Int. J. Fertil. Steril."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1111\/rda.13378","article-title":"Effects of melatonin on oocyte developmental competence and the role of melatonin receptor 1 in juvenile goats","volume":"54","author":"Catala","year":"2019","journal-title":"Reprod. Domest. Anim."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Tian, X., Wang, F., Zhang, L., He, C., Ji, P., Wang, J., Zhang, Z., Lv, D., Abulizi, W., and Wang, X. (2017). Beneficial effects of melatonin on the in vitro maturation of sheep oocytes and its relation to melatonin receptors. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18040834"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e12532","DOI":"10.1111\/jpi.12532","article-title":"Melatonin protects against paraquat-induced damage during in vitro maturation of bovine oocytes","volume":"66","author":"Pang","year":"2019","journal-title":"J. Pineal Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Wang, Y., and Zeng, S. (2018). Melatonin Promotes Ubiquitination of Phosphorylated pro-apoptotic protein Bcl-2-interacting mediator of cell death-extra long (BimEL) in porcine granulosa cells. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113431"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Yang, M., Tao, J., Chai, M., Wu, H., Wang, J., Li, G., He, C., Xie, L., Ji, P., and Dai, Y. (2017). Melatonin improves the quality of inferior bovine oocytes and promoted their subsequent IVF embryo development: Mechanisms and Results. Molecules, 22.","DOI":"10.3390\/molecules22122059"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Tian, X., Wang, F., Zhang, L., Ji, P., Wang, J., Lv, D., Li, G., Chai, M., Lian, Z., and Liu, G. (2017). Melatonin promotes the in vitro development of microinjected pronuclear mouse embryos via its anti-oxidative and anti-apoptotic effects. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18050988"},{"key":"ref_70","first-page":"108","article-title":"Evaluating the effect of melatonin on HAS2, and PGR expression, as well as cumulus expansion, and fertility potential in mice","volume":"20","author":"Ezzati","year":"2018","journal-title":"Cell. J."},{"key":"ref_71","first-page":"3897","article-title":"Melatonin prevents deterioration in quality by preserving epigenetic modifications of porcine oocytes after prolonged culture","volume":"10","author":"Nie","year":"2018","journal-title":"Aging (Albany N.Y.)"},{"key":"ref_72","first-page":"41","article-title":"Ovarian aging and implications for fertility female health","volume":"37","author":"Younis","year":"2012","journal-title":"Minerva Endocrinol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s00439-002-0852-x","article-title":"Maternal aging and chromosomal abnormalities: New data drawn from in vitro unfertilized human oocytes","volume":"112","author":"Pellestor","year":"2003","journal-title":"Hum. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s13048-019-0529-x","article-title":"Mitochondrial dysfunction and endoplasmic reticulum stress involved in oocyte aging: An analysis using single-cell RNA-sequencing of mouse oocytes","volume":"12","author":"Zhang","year":"2019","journal-title":"J. Ovarian. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1095\/biolreprod.110.088583","article-title":"Oxidative damage increases and antioxidant gene expression decreases with aging in the mouse ovary","volume":"84","author":"Lim","year":"2011","journal-title":"Biol. Reprod."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e12381","DOI":"10.1111\/jpi.12381","article-title":"Long-term melatonin treatment delays ovarian aging","volume":"62","author":"Tamura","year":"2017","journal-title":"J. Pineal Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"35165","DOI":"10.1038\/srep35165","article-title":"Melatonin improves age-induced fertility decline and attenuates ovarian mitochondrial oxidative stress in mice","volume":"6","author":"Song","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e12550","DOI":"10.1111\/jpi.12550","article-title":"Melatonin regulates the activities of ovary and delays the fertility decline in female animals via MT1\/AMPK pathway","volume":"66","author":"Zhang","year":"2019","journal-title":"J. Pineal Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/3\/1135\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:56:00Z","timestamp":1760172960000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/3\/1135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,8]]},"references-count":78,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["ijms21031135"],"URL":"https:\/\/doi.org\/10.3390\/ijms21031135","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,8]]}}}