{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T13:43:52Z","timestamp":1783950232547,"version":"3.55.0"},"reference-count":67,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,30]],"date-time":"2021-05-30T00:00:00Z","timestamp":1622332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health (Ricerca Corrente 2019, 2020) and RFFI grant","award":["18-54-06012"],"award-info":[{"award-number":["18-54-06012"]}]},{"name":"SDF (Azerbaijan) grant","award":["EIF-KETPL-2-2015-1(25)-56\/36\/3-M-54"],"award-info":[{"award-number":["EIF-KETPL-2-2015-1(25)-56\/36\/3-M-54"]}]},{"name":"SDF (Azerbaijan) grant","award":["EIF-BGM-4-RFTF-1\/2017-21\/19\/3"],"award-info":[{"award-number":["EIF-BGM-4-RFTF-1\/2017-21\/19\/3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Embryogenesis is a complex multi-stage process regulated by various signaling molecules including pineal and extrapineal melatonin (MT). Extrapineal MT is found in the placenta and ovaries, where it carries out local hormonal regulation. MT is necessary for normal development of oocytes, fertilization and subsequent development of human, animal and avian embryos. This review discusses the role of MT as a regulator of preimplantation development of the embryo and its implantation into endometrial tissue, followed by histo-, morpho- and organogenesis. MT possesses pronounced antioxidant properties and helps to protect the embryo from oxidative stress by regulating the expression of the NFE2L2, SOD1, and GPX1 genes. MT activates the expression of the ErbB1, ErbB4, GJA1, POU5F1, and Nanog genes which are necessary for embryo implantation and blastocyst growth. MT induces the expression of vascular endothelial growth factor (VEGF) and its type 1 receptor (VEGF-R1) in the ovaries, activating angiogenesis. Given the increased difficulties in successful fertilization and embryogenesis with age, it is of note that MT slows down ovarian aging by increasing the transcription of sirtuins. MT administration to patients suffering from infertility demonstrates an increase in the effectiveness of in vitro fertilization. Thus, MT may be viewed as a key factor in embryogenesis regulation, including having utility in the management of infertility.<\/jats:p>","DOI":"10.3390\/ijms22115885","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T00:22:15Z","timestamp":1622420535000},"page":"5885","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Melatonin, Its Beneficial Effects on Embryogenesis from Mitigating Oxidative Stress to Regulating Gene Expression"],"prefix":"10.3390","volume":"22","author":[{"given":"Dmitry","family":"Ivanov","sequence":"first","affiliation":[{"name":"Department of Neonatology, Saint-Petersburg State Pediatric Medical University, Litovskaya Str., 2, 194100 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3535-7635","authenticated-orcid":false,"given":"Gianluigi","family":"Mazzoccoli","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Division of Internal Medicine and Chronobiology Laboratory, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7243-0817","authenticated-orcid":false,"given":"George","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, CRC Scotland & London, London E14 6JE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5156-5421","authenticated-orcid":false,"given":"Natalia","family":"Linkova","sequence":"additional","affiliation":[{"name":"Department of Biogerontology, Saint Petersburg Institute of Bioregulation and Gerontology, 197110 St. Petersburg, Russia"},{"name":"Department of Therapy, Geriatry and Anti-Aging Medicine, Academy of Postgraduate Education, Federal Medical Biological Agency, 220013 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasiia","family":"Dyatlova","sequence":"additional","affiliation":[{"name":"Department of Biogerontology, Saint Petersburg Institute of Bioregulation and Gerontology, 197110 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8134-5104","authenticated-orcid":false,"given":"Ekaterina","family":"Mironova","sequence":"additional","affiliation":[{"name":"Department of Biogerontology, Saint Petersburg Institute of Bioregulation and Gerontology, 197110 St. Petersburg, Russia"},{"name":"Center of Molecular Biomedicine, Saint-Petersburg Institute of Phthisiopulmonology, Lygovsky Ave. 2-4, 191036 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8682-9909","authenticated-orcid":false,"given":"Victoria","family":"Polyakova","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Saint-Petersburg State Pediatric Medical University, Litovskaya Str., 2, 194100 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Kvetnoy","sequence":"additional","affiliation":[{"name":"Center of Molecular Biomedicine, Saint-Petersburg Institute of Phthisiopulmonology, Lygovsky Ave. 2-4, 191036 St. Petersburg, Russia"},{"name":"Department of Pathology, Saint-Petersburg State University, University Embankment, 7\/9, 199034 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inna","family":"Evsyukova","sequence":"additional","affiliation":[{"name":"Department of Newborns\u2019 Pathology, Ott Research Institute of Obstetrics, Gynecology and Reproductology, Mendeleyevskaya Liniya, 3, 199034 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalucia","family":"Carbone","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Division of Internal Medicine and Chronobiology Laboratory, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruslan","family":"Nasyrov","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Saint-Petersburg State Pediatric Medical University, Litovskaya Str., 2, 194100 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,30]]},"reference":[{"key":"ref_1","first-page":"3","article-title":"Human Embryogenesis: Overview","volume":"550","author":"Vaillancourt","year":"2009","journal-title":"Adv. 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