{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T12:41:17Z","timestamp":1792932077333,"version":"4.5.0"},"reference-count":134,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,31]],"date-time":"2019-12-31T00:00:00Z","timestamp":1577750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["0708\/2018"],"award-info":[{"award-number":["0708\/2018"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2019\/00906-6"],"award-info":[{"award-number":["2019\/00906-6"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The development of the endometrium is a cyclic event tightly regulated by hormones and growth factors to coordinate the menstrual cycle while promoting a suitable microenvironment for embryo implantation during the \u201creceptivity window\u201d. Many women experience uterine failures that hamper the success of conception, such as endometrium thickness, endometriosis, luteal phase defects, endometrial polyps, adenomyosis, viral infection, and even endometrial cancer; most of these disturbances involve changes in endocrine components or cell damage. The emerging evidence has proven that circadian rhythm deregulation followed by low circulating melatonin is associated with low implantation rates and difficulties to maintain pregnancy. Given that melatonin is a circadian-regulating hormone also involved in the maintenance of uterine homeostasis through regulation of numerous pathways associated with uterine receptivity and gestation, the success of female reproduction may be dependent on the levels and activity of uterine and placental melatonin. Based on the fact that irregular production of maternal and placental melatonin is related to recurrent spontaneous abortion and maternal\/fetal disturbances, melatonin replacement may offer an excellent opportunity to restore normal physiological function of the affected tissues. By alleviating oxidative damage in the placenta, melatonin favors nutrient transfer and improves vascular dynamics at the uterine\u2013placental interface. This review focuses on the main in vivo and in vitro functions of melatonin on uterine physiological processes, such as decidualization and implantation, and also on the feto-maternal tissues, and reviews how exogenous melatonin functions from a mechanistic standpoint to preserve the organ health. New insights on the potential signaling pathways whereby melatonin resists preeclampsia and endometriosis are further emphasized in this review.<\/jats:p>","DOI":"10.3390\/ijms21010300","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T04:43:03Z","timestamp":1578026583000},"page":"300","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["Melatonin Promotes Uterine and Placental Health: Potential Molecular Mechanisms"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0199-3396","authenticated-orcid":false,"given":"Luiz Gustavo","family":"de Almeida Chuffa","sequence":"first","affiliation":[{"name":"Department of Anatomy-IBB\/UNESP, Institute of Biosciences of Botucatu, Univ. Estadual Paulista, Botucatu, S\u00e3o Paulo 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Antonio","family":"Lupi","sequence":"additional","affiliation":[{"name":"Department of Anatomy-IBB\/UNESP, Institute of Biosciences of Botucatu, Univ. Estadual Paulista, Botucatu, S\u00e3o Paulo 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0593-9335","authenticated-orcid":false,"given":"Maira Smaniotto","family":"Cucielo","sequence":"additional","affiliation":[{"name":"Department of Anatomy-IBB\/UNESP, Institute of Biosciences of Botucatu, Univ. Estadual Paulista, Botucatu, S\u00e3o Paulo 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrique Spaulonci","family":"Silveira","sequence":"additional","affiliation":[{"name":"Department of Anatomy-IBB\/UNESP, Institute of Biosciences of Botucatu, Univ. Estadual Paulista, Botucatu, S\u00e3o Paulo 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russel J.","family":"Reiter","sequence":"additional","affiliation":[{"name":"Department of Cellular and Structural Biology, UT Health, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7461-8773","authenticated-orcid":false,"given":"F\u00e1bio Rodrigues Ferreira","family":"Seiva","sequence":"additional","affiliation":[{"name":"Department of Biology and Technology\u2014UENP\/CLM\u2014Universidade Estadual do Norte do Paran\u00e1, Bandeirantes, Paran\u00e1 86360-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1093\/humrep\/dew099","article-title":"Endometrial preparation: Effect of estrogen dose and administration route on reproductive outcomes in oocyte donation cycles with fresh embryo transfer","volume":"31","author":"Madero","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.fertnstert.2019.02.008","article-title":"Uterine polyps, adenomyosis, leiomyomas, and endometrial receptivity","volume":"111","author":"Munro","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5468","DOI":"10.1128\/MCB.00342-07","article-title":"Bmp2 is critical for the murine uterine decidual response","volume":"27","author":"Lee","year":"2007","journal-title":"Mol. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1172\/JCI1597","article-title":"HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium","volume":"101","author":"Taylor","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_5","first-page":"1129","article-title":"Sex steroids mediate HOXA11 expression in the human peri-implantation endometrium","volume":"84","author":"Taylor","year":"1999","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"a023002","DOI":"10.1101\/cshperspect.a023002","article-title":"The role of Hox genes in female reproductive tract development, adult function, and fertility","volume":"6","author":"Du","year":"2015","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ng, Y.H., Rome, S., Jalabert, A., Forterre, A., Singh, H., Hincks, C.L., and Salamonsen, L.A. (2013). Endometrial exosomes\/microvesicles in the uterine microenvironment: A new paradigm for embryo-endometrial cross talk at implantation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058502"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1111\/j.1600-0897.2012.01181.x","article-title":"A subset of human uterine endometrial macrophages is alternatively activated","volume":"68","author":"Jensen","year":"2012","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1210\/er.2014-1045","article-title":"Cyclic decidualization of the human endometrium in reproductive health and failure","volume":"35","author":"Gellersen","year":"2014","journal-title":"Endocr. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s004410000198","article-title":"Expression of vascular endothelial growth factor by granulated metrial gland cells in pregnant murine uteri","volume":"300","author":"Wang","year":"2000","journal-title":"Cell Tissue Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"16","DOI":"10.4110\/in.2015.15.1.16","article-title":"Immune cells in the female reproductive tract","volume":"15","author":"Lee","year":"2015","journal-title":"Immune Netw."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.rbmo.2017.03.019","article-title":"Uterine peristalsis and fertility: Current knowledge and future perspectives: A review and meta-analysis","volume":"35","author":"Kuijsters","year":"2017","journal-title":"Reprod. Biomed. Online"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"48","DOI":"10.2741\/1196","article-title":"The mammalian circadian clock: A network of gene expression","volume":"9","author":"Albrecht","year":"2004","journal-title":"Front. Biosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1002\/0470090839.ch15","article-title":"Expression of clock gene products in the suprachiasmatic nucleus in relation to circadian behaviour","volume":"253","author":"Hastings","year":"2003","journal-title":"Novartis Found. Symp."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5624","DOI":"10.1210\/en.2007-0660","article-title":"Minireview: The circadian clockwork of the suprachiasmatic nuclei\u2014Analysis of a cellular oscillator that drives endocrine rhythms","volume":"148","author":"Maywood","year":"2007","journal-title":"Endocrinology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1177\/0748730405277232","article-title":"Differential control of Bmal1 circadian transcription by REV-ERB and ROR nuclear receptors","volume":"20","author":"Guillaumond","year":"2005","journal-title":"J. Biol. Rhythm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1002\/bdrc.20101","article-title":"Circadian clocks during embryonic and fetal development","volume":"81","author":"Valenzuela","year":"2007","journal-title":"Birth Defects Res. C Embryo Today"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1620\/tjem.221.287","article-title":"The uterus sustains stable biological clock during pregnancy","volume":"221","author":"Akiyama","year":"2010","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"416","DOI":"10.3109\/07420528.2014.986576","article-title":"Embryonic development and maternal regulation of murine circadian clock function","volume":"32","author":"Landgraf","year":"2015","journal-title":"Chronobiol. Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1096\/fj.14-267195","article-title":"The clock protein period 2 synchronizes mitotic expansion and decidual transformation of human endometrial stromal cells","volume":"29","author":"Muter","year":"2015","journal-title":"FASEB J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"C528","DOI":"10.1152\/ajpcell.00220.2014","article-title":"Inhibitory role of REV-ERB\u03b1 in the expression of bone morphogenetic protein gene family in rat uterus endometrium stromal cells","volume":"308","author":"Tasaki","year":"2015","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"E650","DOI":"10.1152\/ajpendo.00533.2014","article-title":"Removal of Rev-erb\u03b1 inhibition contributes to the prostaglandin G\/H synthase 2 expression in rat endometrial stromal cells","volume":"308","author":"Isayama","year":"2015","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e12663","DOI":"10.14814\/phy2.12663","article-title":"The nuclear receptor REV-ERB\u03b1 represses the transcription of growth\/differentiation factor 10 and 15 genes in rat endometrium stromal cells","volume":"4","author":"Zhao","year":"2016","journal-title":"Physiol. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1007\/s00114-003-0468-6","article-title":"Light, timing of biological rhythms, and chronodisruption in man","volume":"90","author":"Erren","year":"2003","journal-title":"Naturwissenschaften"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1210\/er.2018-00084","article-title":"Melatonin as a hormone: New physiological and clinical insights","volume":"39","author":"Amaral","year":"2018","journal-title":"Endocr Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neures.2014.03.005","article-title":"The in vitro maintenance of clock genes expression within the rat pineal gland under standard and norepinephrine-synchronized stimulation","volume":"81-82","year":"2014","journal-title":"Neurosci. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3335","DOI":"10.1046\/j.1432-1033.2003.03708.x","article-title":"Characterization of the serotoninergic system in the C57BL\/6 mouse skin","volume":"270","author":"Slominski","year":"2003","journal-title":"Eur. J. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1096\/fj.04-2079rev","article-title":"The cutaneous serotoninergic\/melatoninergic system: Securing a place under the sun","volume":"19","author":"Slominski","year":"2005","journal-title":"FASEB J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1600-079X.2009.00729.x","article-title":"Sirtuins, melatonin and circadian rhythms: Building a bridge between aging and cancer","volume":"48","author":"Reiter","year":"2010","journal-title":"J. Pineal Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/jpi.12189","article-title":"Melatonin feedback on clock genes: A theory involving the proteasome","volume":"58","author":"Vriend","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"133","DOI":"10.32794\/mr11250026","article-title":"Clock genes and the role of melatonin in cancer cells: An overview","volume":"2","author":"Chuffa","year":"2019","journal-title":"Melatonin Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3872","DOI":"10.1021\/acs.jproteome.6b00713","article-title":"Quantitative proteomic profiling reveals that diverse metabolic pathways are influenced by melatonin in an in vivo model of ovarian carcinoma","volume":"15","author":"Chuffa","year":"2016","journal-title":"J. Proteome Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/jpi.12360","article-title":"Melatonin as an antioxidant: Under promises but over delivers","volume":"61","author":"Reiter","year":"2016","journal-title":"J. Pineal Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1007\/s00018-018-2963-0","article-title":"Mitochondrial functions and melatonin: A tour of the reproductive cancers","volume":"76","author":"Seiva","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1385\/ENDO:27:2:101","article-title":"Functional MT1 and MT2 melatonin receptors in mammals","volume":"27","author":"Dubocovich","year":"2005","journal-title":"Endocrine"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1096\/fj.13-242040","article-title":"ROR\u03b1 and ROR\u03b3 are expressed in human skin and serve as receptors for endogenously produced noncalcemic 20-hydroxy-and 20,23-dihydroxyvitamin D","volume":"28","author":"Slominski","year":"2014","journal-title":"FASEB J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1002\/bies.201600204","article-title":"ROR\u03b1 is not a receptor for melatonin","volume":"38","author":"Slominski","year":"2016","journal-title":"Bioessays"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2742","DOI":"10.1096\/fj.12-224691","article-title":"Metabolism of melatonin and biological activity of intermediates of melatoninergic pathway in human skin cells","volume":"27","author":"Kim","year":"2013","journal-title":"FASEB J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1111\/exd.13208","article-title":"Metabolism of melatonin in the skin: Why is it important?","volume":"26","author":"Slominski","year":"2017","journal-title":"Exp. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.reprotox.2008.03.005","article-title":"Melatonin and pregnancy in the human","volume":"25","author":"Tamura","year":"2008","journal-title":"Reprod. Toxicol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/jog.12177","article-title":"Melatonin and female reproduction","volume":"40","author":"Tamura","year":"2014","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s10495-015-1195-0","article-title":"Does melatonin influence the apoptosis in rat uterus of animals exposed to continuous light?","volume":"21","author":"Ferreira","year":"2016","journal-title":"Apoptosis"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1093\/humupd\/dmt054","article-title":"Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology","volume":"20","author":"Reiter","year":"2014","journal-title":"Hum. Reprod. Update"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4618","DOI":"10.1210\/en.2006-0628","article-title":"Maternal melatonin effects on clock gene expression in a nonhuman primate fetus","volume":"147","author":"Rocco","year":"2006","journal-title":"Endocrinology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.mce.2011.07.039","article-title":"Circadian rhythms in the fetus","volume":"349","author":"Mendez","year":"2012","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1093\/humrep\/dez082","article-title":"Melatonin activity and receptor expression in endometrial tissue and endometriosis","volume":"34","author":"Mosher","year":"2019","journal-title":"Hum. Reprod."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1210\/jc.2008-1723","article-title":"Melatonin synergizes with oxytocin to enhance contractility of human myometrial smooth muscle cells","volume":"94","author":"Sharkey","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.fertnstert.2014.06.020","article-title":"Clinical significance of melatonin receptors in the human myometrium","volume":"102","author":"Olcese","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1093\/molehr\/gav023","article-title":"Circadian clock regulation of melatonin MTNR1B receptor expression in human myometrial smooth muscle cells","volume":"21","author":"Beesley","year":"2015","journal-title":"Mol. Hum. Reprod."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1034\/j.1600-079X.2002.02898.x","article-title":"Variations of mt1 melatonin receptor density in the rat uterus during decidualization, the estrous cycle and in response to exogenous steroid treatment","volume":"33","author":"Zhao","year":"2002","journal-title":"J. Pineal Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1002\/mrd.1147","article-title":"mt(1) Receptor-mediated antiproliferative effects of melatonin on the rat uterine antimesometrial stromal cells","volume":"61","author":"Zhao","year":"2002","journal-title":"Mol. Reprod. Dev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/j.fertnstert.2007.03.050","article-title":"Effects of melatonin on the endometrial morphology and embryo implantation in rats","volume":"89","author":"Dair","year":"2008","journal-title":"Fertil. Steril."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/S0278-5846(99)00110-4","article-title":"Modulation of estrous cycle and LH, FSH and melatonin levels by pinealectomy and sham-pinealectomy in female rats","volume":"24","author":"Dardes","year":"2000","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1016\/j.fertnstert.2005.12.018","article-title":"Glycodelin is present in pinopodes of receptive-phase human endometrium and is associated with down-regulation of progesterone receptor B","volume":"85","author":"Mandelin","year":"2006","journal-title":"Fertil. Steril."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/nature05993","article-title":"p53 regulates maternal reproduction through LIF","volume":"450","author":"Hu","year":"2007","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/359076a0","article-title":"Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor","volume":"359","author":"Stewart","year":"1992","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1111\/jpi.12216","article-title":"Melatonin-related genes expressed in the mouse uterus during early gestation promote embryo implantation","volume":"58","author":"He","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.3892\/etm.2016.3692","article-title":"Increased apoptosis rate of human decidual cells and cytotrophoblasts in patients with recurrent spontaneous abortion as a result of abnormal expression of CDKN1A and Bax","volume":"12","author":"Lv","year":"2016","journal-title":"Exp. Ther. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1080\/10520295.2019.1605456","article-title":"Effect of melatonin on torsion and reperfusion induced pathogenesis of rat uterus","volume":"94","author":"Saat","year":"2019","journal-title":"Biotech. Histochem."},{"key":"ref_60","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_61","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1007\/s12033-016-9968-4","article-title":"Extended culture of encapsulated human blastocysts in alginate hydrogel containing decidualized endometrial stromal cells in the presence of melatonin","volume":"58","author":"Arjmand","year":"2016","journal-title":"Mol. Biotechnol."},{"key":"ref_62","first-page":"599","article-title":"Melatonin pretreated blastocysts along with calcitonin administration improved implantation by upregulation of heparin binding-epidermal growth factor expression in murine endometrium","volume":"19","author":"Moshkdanian","year":"2018","journal-title":"Cell J."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Guan, S., Xie, L., Ma, T., Lv, D., Jing, W., Tian, X., Song, Y., Liu, Z., Xiao, X., and Liu, G. (2017). Effects of melatonin on early pregnancy in mouse: Involving the regulation of StAR, Cyp11a1, and Ihh expression. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081637"},{"key":"ref_64","first-page":"655","article-title":"Melatonin upregulates ErbB1 and ErbB4, two primary implantation receptors, in pre-implantation mouse embryos","volume":"20","author":"Moshkdanian","year":"2017","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"18315","DOI":"10.1073\/pnas.0707909104","article-title":"Maternal heparin-binding-EGF deficiency limits pregnancy success in mice","volume":"104","author":"Xie","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s12958-017-0297-7","article-title":"Effects of melatonin administration on embryo implantation and offspring growth in mice under different schedules of photoperiodic exposure","volume":"15","author":"Zhang","year":"2017","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1093\/humupd\/dmm009","article-title":"Estrogen and the endometrium: Lessons learned from gene expression profiling in rodents and human","volume":"13","author":"Groothuis","year":"2007","journal-title":"Hum. Reprod. Update"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1101\/gad.9.18.2266","article-title":"Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities","volume":"9","author":"Lydon","year":"1995","journal-title":"Genes Dev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5310","DOI":"10.1210\/endo.140.11.7148","article-title":"Differential uterine expression of estrogen and progesterone receptors correlates with uterine preparation for implantation and decidualization in the mouse","volume":"140","author":"Tan","year":"1999","journal-title":"Endocrinology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S1043-6618(03)00014-8","article-title":"Effect of melatonin on estrogen and progesterone receptors in relation to uterine contraction in rats","volume":"47","author":"Hamada","year":"2003","journal-title":"Pharmacol. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/1477-7827-9-108","article-title":"Melatonin reduces LH, 17 beta-estradiol and induces differential regulation of sex steroid receptors in reproductive tissues during rat ovulation","volume":"9","author":"Chuffa","year":"2011","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1600-079X.1999.tb00598.x","article-title":"Changes in nocturnal pineal melatonin synthesis during the perimenopausal period: Relation to estrogen levels in female rats","volume":"27","author":"Okatani","year":"1999","journal-title":"J. Pineal Res."},{"key":"ref_73","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_74","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.fertnstert.2014.06.014","article-title":"Melatonin and the circadian system: Contributions to successful female reproduction","volume":"102","author":"Reiter","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Carlomagno, G., Minini, M., Tilotta, M., and Unfer, V. (2018). From implantation to birth: Insight into molecular melatonin functions. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092802"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/j.1600-079X.2005.00244.x","article-title":"Melatonin as a local regulator of human placental function","volume":"39","author":"Iwasaki","year":"2005","journal-title":"J. Pineal Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/j.1600-079X.2012.01012.x","article-title":"Placental melatonin production and melatonin receptor expression are altered in preeclampsia: New insights into the role of this hormone in pregnancy","volume":"53","author":"Lanoix","year":"2012","journal-title":"J. Pineal Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3109\/09513590.2013.849238","article-title":"Clinical relevance of melatonin in ovarian and placental physiology: A review","volume":"30","author":"Reiter","year":"2014","journal-title":"Gynecol. Endocrinol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.placenta.2012.03.008","article-title":"A rhythmic placenta? Circadian variation, clock genes and placental function","volume":"33","author":"Waddell","year":"2012","journal-title":"Placenta"},{"key":"ref_80","first-page":"251","article-title":"Maternal and placental melatonin: Actions and implication for successful pregnancies","volume":"66","author":"Soliman","year":"2014","journal-title":"Minerva Ginecol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"825802","DOI":"10.1155\/2015\/825802","article-title":"Circadian system and melatonin hormone: Risk factors for complications during pregnancy","volume":"2015","author":"Valenzuela","year":"2015","journal-title":"Obstet. Gynecol. Int."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e12591","DOI":"10.1111\/jpi.12591","article-title":"Melatonin for prevention of placental malperfusion and fetal compromise associated with intrauterine inflammation-induced oxidative stress in a mouse model","volume":"67","author":"Lee","year":"2019","journal-title":"J. Pineal Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e13151","DOI":"10.1111\/aji.13151","article-title":"Administration of melatonin for prevention of preterm birth and fetal brain injury associated with premature birth in a mouse model","volume":"82","author":"Lee","year":"2019","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_84","first-page":"1","article-title":"Melatonin decreases and cytokines increase in women with placental insufficiency","volume":"25","author":"Berbets","year":"2019","journal-title":"J. Matern Fetal Neonatal Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1053\/j.semperi.2009.02.010","article-title":"The global impact of pre-eclampsia and eclampsia","volume":"33","author":"Duley","year":"2009","journal-title":"Semin. Perinatol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1034\/j.1600-079X.2001.300104.x","article-title":"Changes of serum melatonin level and its relationship to feto-placental unit during pregnancy","volume":"30","author":"Nakamura","year":"2001","journal-title":"J. Pineal Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/jhh.2016.37","article-title":"The reduction in circulating levels of melatonin may be associated with the development of preeclampsia","volume":"30","author":"Zeng","year":"2016","journal-title":"J. Hum. Hypertens."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/jpi.12236","article-title":"Placental melatonin system is present throughout pregnancy and regulates villous trophoblast differentiation","volume":"59","author":"Soliman","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e12520","DOI":"10.1111\/jpi.12520","article-title":"Melatonin modulates autophagy and inflammation protecting human placental trophoblast from hypoxia\/reoxygenation","volume":"65","author":"Ruano","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Sagrillo-Fagundes, L., Bienvenue-Pariseault, J., and Vaillancourt, C. (2019). Melatonin: The smart molecule that differentially modulates autophagy in tumor and normal placental cells. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0202458"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e12508","DOI":"10.1111\/jpi.12508","article-title":"Melatonin improves endothelial function in vitro and prolongs pregnancy in women with early-onset preeclampsia","volume":"65","author":"Hobson","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.arcmed.2017.08.007","article-title":"Effects of melatonin on blood pressure, oxidative stress and placental expressions of TNF\u03b1, IL-6, VEGF and sFlt-1 in RUPP rat model of preeclampsia","volume":"48","author":"Uzun","year":"2017","journal-title":"Arch. Med. Res."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Hannan, N.J., Binder, N.K., Beard, S., Nguyen, T.V., Kaitu\u2019u-Lino, T.J., and Tong, S. (2018). Melatonin enhances antioxidant molecules in the placenta, reduces secretion of soluble fms-like tyrosine kinase 1 (sFLT) from primary trophoblast but does not rescue endothelial dysfunction: An evaluation of its potential to treat preeclampsia. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0187082"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1146\/annurev-cellbio-101512-122326","article-title":"Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles","volume":"30","author":"Colombo","year":"2014","journal-title":"Annu Rev. Cell Dev. Biol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.placenta.2017.08.001","article-title":"Melatonin prevents preeclamptic sera and antiphospholipid antibodies inducing the production of reactive nitrogen species and extrusion of toxic trophoblastic debris from first trimester placentae","volume":"58","author":"Zhao","year":"2017","journal-title":"Placenta"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1177\/1933719117704908","article-title":"Melatonin improves mitochondrial respiration in syncytiotrophoblasts from placentas of obese women","volume":"25","author":"Ireland","year":"2018","journal-title":"Reprod. Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e12525","DOI":"10.1111\/jpi.12525","article-title":"Melatonin and inflammation-Story of a double-edged blade","volume":"65","author":"Hardeland","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Man, G.C.W., Zhang, T., Chen, X., Wang, J., Wu, F., Liu, Y., Wang, C.C., Cheong, Y., and Li, T.C. (2017). The regulations and role of circadian clock and melatonin in uterine receptivity and pregnancy\u2014An immunological perspective. Am. J. Reprod. Immunol., 78.","DOI":"10.1111\/aji.12715"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1399-0039.2004.00170.x","article-title":"Human uterine leukocytes and pregnancy","volume":"63","author":"Trundley","year":"2004","journal-title":"Tissue Antigens"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4750","DOI":"10.1128\/IAI.00287-06","article-title":"The circadian clock Period 2 gene regulates gamma interferon production of NK cells in host response to lipopolysaccharide-induced endotoxic shock","volume":"74","author":"Liu","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/j.1600-0897.2008.00674.x","article-title":"Changes in the subpopulation of CD25+ CD4+ and FOXP3+ regulatory T cells in decidua with respect to the progression of labor at term and the lack of analogical changes in the subpopulation of suppressive B7-H4 macrophages\u2014A preliminary report","volume":"61","author":"Galazka","year":"2009","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0165-0378(00)00060-7","article-title":"Cytokine network at the feto-maternal interface","volume":"47","author":"Saito","year":"2000","journal-title":"J. Reprod. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000069464","article-title":"Circadian secretions of IL-2, IL-12, IL-6 and IL-10 in relation to the light\/dark rhythm of the pineal hormone melatonin in healthy humans","volume":"16","author":"Lissoni","year":"1998","journal-title":"Nat. Immun."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1146\/annurev-immunol-032712-100003","article-title":"Immunology of the maternal-fetal interface","volume":"31","author":"Erlebacher","year":"2013","journal-title":"Annu. Rev. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/jpi.12075","article-title":"The role of melatonin in the cells of the innate immunity: A review","volume":"55","author":"Calvo","year":"2013","journal-title":"J. Pineal Res."},{"key":"ref_106","first-page":"1026","article-title":"Tryptophan administration in rats enhances phagocytic function and reduces oxidative metabolism","volume":"29","author":"Sanchez","year":"2008","journal-title":"Neuro Endocrinol. Lett."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1111\/j.1600-0897.2010.00852.x","article-title":"Th1\/Th2\/Th17 and regulatory T-cell paradigm in pregnancy","volume":"63","author":"Saito","year":"2010","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1007\/s10517-016-3242-4","article-title":"Role of melatonin in the regulation of differentiation of T cells producing interleukin-17 (Th17)","volume":"160","author":"Kuklina","year":"2016","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1007\/s10517-018-4013-1","article-title":"Role of endogenous melatonin in the regulation of Th17\/Treg balance during pregnancy","volume":"164","author":"Glebezdina","year":"2018","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1056\/NEJMra0804690","article-title":"Endometriosis","volume":"360","author":"Bulun","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e137","DOI":"10.1016\/j.fertnstert.2019.08.082","article-title":"Reprint of: Impact of endometriosis on quality of life and work productivity: A multicenter study across ten countries","volume":"112","author":"Nnoaham","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e153","DOI":"10.1016\/j.fertnstert.2019.08.083","article-title":"Reprint of: Pathogenesis and pathophysiology of endometriosis","volume":"112","author":"Burney","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1210\/er.2018-00242","article-title":"Endometriosis","volume":"40","author":"Bulun","year":"2019","journal-title":"Endocr. Rev."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1097\/EDE.0b013e31816b7378","article-title":"Shift work, hCLOCK T3111C polymorphism, and endometriosis risk","volume":"19","author":"Marino","year":"2008","journal-title":"Epidemiology."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ejogrb.2010.06.012","article-title":"Effects of pinealectomy and melatonin supplementation on endometrial explants in a rat model","volume":"153","author":"Koc","year":"2010","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1016\/j.fertnstert.2009.09.021","article-title":"The effects of letrozole and melatonin on surgically induced endometriosis in a rat model: A preliminary study","volume":"93","author":"Yildirim","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"25","DOI":"10.12891\/ceog2035.2016","article-title":"The effects of melatonin on endometriotic lesions induced by implanting human endometriotic cells in the first SCID-mouse endometriosis-model developed in Turkey","volume":"43","author":"Yesildaglar","year":"2016","journal-title":"Clin. Exp. Obstet. Gynecol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s00404-014-3466-3","article-title":"The effects of different doses of melatonin treatment on endometrial implants in an oophorectomized rat endometriosis model","volume":"291","author":"Cetinkaya","year":"2015","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.fertnstert.2007.04.023","article-title":"Regression of endometrial explants in a rat model of endometriosis treated with melatonin","volume":"89","author":"Oral","year":"2008","journal-title":"Fertil. Steril."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s00404-014-3599-4","article-title":"Melatonin causes regression of endometriotic implants in rats by modulating angiogenesis, tissue levels of antioxidants and matrix metalloproteinases","volume":"292","author":"Yilmaz","year":"2015","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/S0015-0282(16)55437-5","article-title":"Early endometriosis invades the extracellular matrix","volume":"58","author":"Spuijbroek","year":"1992","journal-title":"Fertil. Steril."},{"key":"ref_122","first-page":"156","article-title":"Melatonin protects against endometriosis via regulation of matrix metalloproteinase-3 and an apoptotic pathway","volume":"49","author":"Paul","year":"2010","journal-title":"J. Pineal Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1111\/j.1600-079X.2007.00547.x","article-title":"Role of melatonin in regulating matrix metalloproteinase-9 via tissue inhibitors of metalloproteinase-1 during protection against endometriosis","volume":"44","author":"Paul","year":"2008","journal-title":"J. Pineal Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.freeradbiomed.2019.03.027","article-title":"Mitochondria and oxidative stress in ovarian endometriosis","volume":"136","author":"Chen","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.freeradbiomed.2019.01.022","article-title":"Mitochondrial translocation of estrogen receptor \u03b2 affords resistance to oxidative insult-induced apoptosis and contributes to the pathogenesis of endometriosis","volume":"134","author":"Liao","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1515\/bmc-2019-0017","article-title":"Endometriosis pathoetiology and pathophysiology: Roles of vitamin A, estrogen, immunity, adipocytes, gut microbiome and melatonergic pathway on mitochondria regulation","volume":"10","author":"Anderson","year":"2019","journal-title":"Biomol. Concepts"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s12958-018-0375-5","article-title":"Melatonin inhibits 17\u03b2-estradiol-induced migration, invasion and epithelial-mesenchymal transition in normal and endometriotic endometrial epithelial cells","volume":"16","author":"Qi","year":"2018","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1016\/j.pain.2013.02.025","article-title":"Efficacy of melatonin in the treatment of endometriosis: A phase II, randomized, double-blind, placebo-controlled trial","volume":"154","author":"Schwertner","year":"2013","journal-title":"Pain"},{"key":"ref_129","first-page":"564","article-title":"The endometrial immune environment of women with endometriosis","volume":"25","author":"Houshdaran","year":"2019","journal-title":"Hum. Reprod. Update"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"e12839","DOI":"10.1111\/aji.12839","article-title":"Pleiotropic roles of melatonin in endometriosis, recurrent spontaneous abortion, and polycystic ovary syndrome","volume":"80","author":"Yang","year":"2018","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/j.1600-079X.1998.tb00550.x","article-title":"Maternal-fetal transfer of melatonin in pregnant women near term","volume":"25","author":"Okatani","year":"1998","journal-title":"J. Pineal Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/s41419-019-1556-7","article-title":"Melatonin as a master regulator of cell death and inflammation: Molecular mechanisms and clinical implications for newborn care","volume":"10","author":"Tarocco","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1080\/09513590.2017.1409713","article-title":"Melatonin concentration in follicular fluid is correlated with antral follicle count (AFC) and in vitro fertilization (IVF) outcomes in women undergoing assisted reproductive technology (ART) procedures","volume":"34","author":"Zheng","year":"2018","journal-title":"Gynecol. Endocrinol."},{"key":"ref_134","first-page":"225","article-title":"Effects of melatonin administration on chemical pregnancy rates of polycystic ovary syndrome patients undergoing intrauterine insemination: A randomized clinical trial","volume":"13","author":"Mokhtari","year":"2019","journal-title":"Int. J. Fertil. 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