The role of melatonin in the implementation of women's reproductive plans: from menarche to the physiological course of the gestational process (literature review)

Authors

DOI:

https://doi.org/10.15574/HW.2025.1(176).7182

Keywords:

melatonin, antioxidant, reproductive function, pregnancy, gestational complications, premature birth, miscarriage

Abstract

The indoleamine hormone melatonin, with its many physiological and biological functions, is now considered an important and essential hormone during pregnancy. Melatonin is an antioxidant, anti-inflammatory agent, free radical scavenger, circadian rhythm regulator, and sleep hormone.

Aim: to analyze the current data on the effect of melatonin on reproductive function, pregnancy and fetal development, and the issues of exogenous melatonin administration in obstetrics and gynaecology.

Recent studies have shown that the placenta can synthesize its melatonin, which acts as an antioxidant and anti-inflammatory agent, providing a stable environment for both mother and fetus. Thanks to its antioxidant properties, the integrity of the placenta is maintained. During physiological pregnancy, the mother's immune system is constantly changing, and melatonin acts as a key anti-inflammatory factor that regulates immune homeostasis in the early and late stages of pregnancy. Excessive production of oxygen and nitrogen metabolites are important mediators of cell and tissue damage. It is melatonin, which is easily transferred from the maternal circulation to the fetus, that may be a protective factor that will prevent free radical damage to the fetus and contribute to better perinatal outcomes. The antioxidant properties of melatonin have been shown to optimize the reproductive physiology of pregnant women by eliminating undesirable oxidative and nitrosative reactions in ovarian, uterine, and placental cells. It is emphasized that melatonin is an important factor for the course of early pregnancy, for the normal development and functioning of the placenta. It has been determined that the circadian release of this hormone is involved in the correction of various pathological conditions that occur during pregnancy: dyssomnia, pre-eclampsia, paroxysmal eclampsia. It has been shown that exogenous melatonin supplementation in pregnant women contributes to the regression of sleep disorders, pre-eclampsia, fetal growth retardation, and normalization of adrenal corticosterone levels.

No conflict of interests was declared by the authors.

References

Abdal Dayem A, Hossain MK, Lee SB, Kim K, Saha SK, Yang GM et al. (2017). The role of reactive oxygen species (ROS) in the biological activities of metallic nanoparticles. Int. J. Mol. Sci 18(1): 120. https://doi.org/10.3390/ijms18010120; PMid:28075405 PMCid:PMC5297754

Acuna-Castroviejo D, Escames G, Venegas C. (2014). Extra-pineal melatonin: sources, regulation, and potential functions. Cell. Mol. Life Sci. 71(16): 2997-3025. https://doi.org/10.1007/s00018-014-1579-2; PMid:24554058 PMCid:PMC11113552

Albrecht U. (2004). The mammalian circadian clock: a network of gene expression. Front. Biosci. 9: 48-55. https://doi.org/10.2741/1196; PMid:14766343

Akiyama S, Ohta H, Watanabe S, Moriya T, Hariu A, Nakahata N et al. (2010). The uterus sustains stable biological clock during pregnancy. Tohoku J. Exp. Med. 221(4): 287-298. https://doi.org/10.1620/tjem.221.287; PMid:20647694

Antolin I, Rodriguez C, Sainz RM, Mayo JC, Uria H, Kotler ML et al. (1996). Neuro-hormone melatonin prevents cell damage: effect on gene expression for antioxidant enzymes. FASEB J. 10: 882-890. https://doi.org/10.1096/fasebj.10.8.8666165; PMid:8666165

Arendt J. (1995). Melatonin and the Mammalian Pineal Gland. Chapman& Hall, London.

Aversa S, Pellegrino S, Barberi I, Reiter RJ, Gitto E. (2012). Potential utility of melatonin as an antioxidant during pregnancy and in the perinatal period. J. Matern. Fetal. Neonatal. Med. 25 (3): 207-221. https://doi.org/10.3109/14767058.2011.573827; PMid:21557691

Baker J, Kimpinski K. (2018). Role of melatonin in blood pressure regulation: an adjunct anti-hypertensive agent. Clin. Exp. Pharmacol. Physiol. 45: 755-766. https://doi.org/10.1111/1440-1681.12942; PMid:29603319

Bates K, Herzog ED. (2020). Maternal-fetal circadian communication during pregnancy. Front. Endocrinol. (Lausanne). 11: 198. https://doi.org/10.3389/fendo.2020.00198; PMid:32351448 PMCid:PMC7174624

Bellipanni G, Bianchi P, Pierpaoli W, Bulian D, Ilyia E. (2001). Effects of melatonin in perimenopausal and menopausal women: A randomized and placebo controlled study. Exp. Gerontol. 36: 297-310. https://doi.org/10.1016/S0531-5565(00)00217-5; PMid:11226744

Bouchlariotou S, Liakopoulos V, Giannopoulou M, Arampatzis S, Eleftheriadis Th, Mertens PR et al. (2014). Melatonin secretion is impaired in women with preeclampsia and an abnormal circadian blood pressure rhythm. Ren. Fail. 36(7): 1001-1007. https://doi.org/10.3109/0886022X.2014.926216; PMid:24932757

Burton GJ, Jauniaux E. Oxidative stress. Best Pract. Res. Clin. Obstet. Gynaecol. (2011). 25(3): 287-299. https://doi.org/10.1016/j.bpobgyn.2010.10.016; PMid:21130690 PMCid:PMC3101336

Burton GJ, Jauniaux E. (2004). Placental oxidative stress: from miscarriage to preeclampsia. J. Soc. Gynecol. Investig. 11(6): 342-352. https://doi.org/10.1016/j.jsgi.2004.03.003; PMid:15350246

Brzezinski A, Rai S, Purohit A, Pandi-Perumal SR. (2021). Melatonin, clock genes, and mammalian reproduction: what is the link? Int. J. Mol. Sci. 22(24): 13240. https://doi.org/10.3390/ijms222413240; PMid:34948038 PMCid:PMC8704059

Cajochen C, Münch M, Kobialka S, Kräuchi K, Steiner R, Oelhafen P et all. (2005). High sensitivity of human melatonin, alertness, thermoregulation, and heart rate to short wavelength light. J. Clin. Endocrinol. Metab. 90(3): 1311-1316. https://doi.org/10.1210/jc.2004-0957; PMid:15585546

Сarrillo-Vico AA, Guerrero JM, Lardone PJ. (2005). Review of the multiple actions of melatonin on the immune system. Endocrine. 27(2): 189-200. https://doi.org/10.1385/ENDO:27:2:189; PMid:16217132

Chen YC, Sheen JM, Tiao MM, Tain YL, Huang LT. (2013). Roles of melatonin in fetal programming in compromised pregnancies. Int. J. Mol. Sci. 14(3): 5380-5401. https://doi.org/10.3390/ijms14035380; PMid:23466884 PMCid:PMC3634509

Chuffa LGA, Lupi LA, Cucielo MS, Silveira HS, Reiter RJ, Seiva FRF. (2019). Melatonin promotes uterine and placental health: potential molecular mechanisms. Int. J. Mol. Sci. 21(1): 300. https://doi.org/10.3390/ijms21010300; PMid:31906255 PMCid:PMC6982088

Dragojevic DS., Jovanovic AM, Dikic S. (2015). Melatonin: a «Higgs boson» in human reproduction. Gynecol. Endocrinol. 31(2): 92-101. https://doi.org/10.3109/09513590.2014.978851; PMid:25377724

Ejaz H, Figaro JK, Woolner AMF, Thottakam BMV, Galley HF. (2020). Maternal serum melatonin increases during pregnancy and falls immediately after delivery implicating the placenta as a major source of melatonin. Front. Endocrinol. (Lausanne) 11: 623038. https://doi.org/10.3389/fendo.2020.623038; PMid:33679607 PMCid:PMC7930478

El-Raey M, Geshi M, Somfai T, Kaneda M, Hirako M, Abdel-Ghaffar AE et al. (2011). Evidence of melatonin synthesis in the cumulus oocyte complexes and its role in enhancing oocyte maturation in vitro in cattle Mol. Reprod. Dev. 78(4): 250-262. https://doi.org/10.1002/mrd.21295; PMid:21381146

Esposito E, Paterniti I, Mazzon E, Bramanti P, Cuzzocrea S. (2010). Melatonin reduces hyperalgesia associated with inflammation. J. Pineal. Res. 49: 321-331. https://doi.org/10.1111/j.1600-079X.2010.00796.x; PMid:20666977

Gauster M, Moser G, Wernitznig S, Kupper N, Huppertz B. (2022). Early human trophoblast development: from morphology to function. Cell. Mol. Life Sci. 79(6): 345. https://doi.org/10.1007/s00018-022-04377-0; PMid:35661923 PMCid:PMC9167809

Galano A, Tan DX, Reite RJ. (2013). On the free radical scavenging activities of melatonin's metabolites, AFMK and AMK J. Pineal. Res. 54: 245-257. https://doi.org/10.1111/jpi.12010; PMid:22998574

Gonzalez-Candia A, Veliz M, Carrasco-Pozo C, Castillo RL, Cardenas JC, Ebensperger G et al. (2019). Antenatal melatonin modulates an enhanced antioxidant/prooxidant ratio in pulmonary hypertensive newborn sheep. Redox. Biol. 22: 101128. https://doi.org/10.1016/j.redox.2019.101128; PMid:30771751 PMCid:PMC6375064

Gitto E, Aversa S, Salpietro CD. (2012). Pain in neonatal intensive care: role of melatonin as an analgesic antioxidant. J. Pineal Res. 52: 291-295. https://doi.org/10.1111/j.1600-079X.2011.00941.x; PMid:22141591

Gitto E, Marseglia L, Manti S. (2013). Protective Role of Melatonin in Neonatal Diseases. Oxidative Medicine and Cellular Longevity. Oxid. Med. Cell. Longev. 2013: 980374. https://doi.org/10.1155/2013/980374; PMid:24349616 PMCid:PMC3852086

Hansson SR, Naav A, Erlandsson L. (2014). Oxidative stress in preeclampsia and the role of free fetal hemoglobin. Front. Physiol. 5: 516. https://doi.org/10.3390/ijms19051496; PMid:29772777 PMCid:PMC5983711

Hardeland R, Poeggeler B. (2003). Non-vertebrate melatonin. J. Pineal. Res. 34: 233-241. https://doi.org/10.1034/j.1600-079X.2003.00040.x; PMid:12662344

Hastings MH, Reddy AB, Garabette M, King VM, Chahad-Ehlers S, O'Brien J et al. (2003). Expression of clock gene products in the suprachiasmatic nucleus in relation to circadian behaviour. Novartis Found Symp. 253: 203-217. https://doi.org/10.1002/0470090839.ch15; PMid:14712923

Hsu CN, Tain YL. (2020). Light and circadian signaling pathway in pregnancy: programming of adult health and disease. Int. J. Mol. Sci. 21(6): 2232. https://doi.org/10.3390/ijms21062232; PMid:32210175 PMCid:PMC7139376

Irmak MK. Topal T, Oter S. (2005). Melatonin seems to be a mediator that transfers the environmental stimuli to oocytes for inheritance of adaptive changes through epigenetic inheritance system. Medical Hypotheses. 2: 1138-1143. https://doi.org/10.1016/j.mehy.2004.12.014; PMid:15823703

Ismail SA, Mowafi HA. (2009). Melatonin provides anxiolysis, enhances analgesia, decreases intraocular pressure, and promotes better operating conditions during cataract surgery under topical anesthesia. Anesth. Analg. 108(4): 1146-1151. https://doi.org/10.1213/ane.0b013e3181907ebe; PMid:19299777

Joseph TT, Schuch V, Hossack DJ, Chakraborty R, Johnson EL. (2024). Melatonin: the placental antioxidant and anti-inflammatory frontiersin. Front. Immunol. 15: 1339304. https://doi.org/10.3389/fimmu.2024.1339304; PMid:38361952 PMCid:PMC10867115

Juan CA, Perez de la Lastra JM, Plou FJ, Perez-Lebena E. (2021). The chemistry of reactive oxygen species (ROS) revisited: outlining their role in biological macromolecules (DNA, lipids and proteins) and induced pathologies. Int. J. Mol. Sci. 22(9): 4642. https://doi.org/10.3390/ijms22094642; PMid:33924958 PMCid:PMC8125527

Jung-Hynes B, Reiter RJ, Ahmad N. (2010). Sirtuins, melatonin and circadian rhythms: building a bridge between aging and cancer. J. Pineal. Res. 48(1): 9-19. https://doi.org/10.1111/j.1600-079X.2009.00729.x; PMid:20025641 PMCid:PMC2948667

Kaneko Y, Hayashi T, Yu S, Tajiri N, Bae EC, Solomita MA et al. (2011). Human amniotic epithelial cells express melatonin receptor MT1, but not melatonin receptor MT2: a new perspective to neuroprotection. J. Pineal. Res. 50: 272-280. https://doi.org/10.1111/j.1600-079X.2010.00837.x; PMid:21269327

Karasek M, Reiter RJ. (2002). Melatonin and aging. Neuroendocrinol. Lett. 23(1): 14-16.

Kivela A. (1991). Serum melatonin during human pregnancy. Acta Endocrinol. (Copenh) 124(3): 233-237. https://doi.org/10.1530/acta.0.1240233

Korkmaz A, Reiter RJ, Topal T, Manchester LC, Oter S, Tan DX. (2009, Jan-Feb). Melatonin: an established antioxidant worthy of use in clinical trials. Mol. Med. 15(1-2): 43-50. https://doi.org/10.2119/molmed.2008.00117; PMid:19011689 PMCid:PMC2582546

Langston-Cox A, Marshall SA, Lu D, Palmer KR, Wallace EM. (2021). Melatonin for the management of preeclampsia: A review. Antioxidants (Basel). 10(3): 376. https://doi.org/10.3390/antiox10030376; PMid:33802558 PMCid:PMC8002171

Lanoix D, Beghdadi H, Lafond J, Vaillancourt C. (2008). Human placental trophoblasts synthesize melatonin and express its receptors. J. Pineal. Res. 45(1): 50-60. https://doi.org/10.1111/j.1600-079X.2008.00555.x; PMid:18312298

Lanoix D, Guerin P, Vaillancourt C. (2012). Placental melatonin production and melatonin receptor expression are altered in preeclampsia: new insights into the role of this hormone in pregnancy. J. Pineal. Res. 53(4): 417-425. https://doi.org/10.1111/j.1600-079X.2012.01012.x; PMid:22686298

Lanoix D, Lacasse AA, Reiter RJ, Vaillancourt C. (2013). Melatonin: the watchdog of villous trophoblast homeostasis against hypoxia/reoxygenation-induced oxidative stress and apoptosis. Mol. Cell. Endocrinol. 381(1-2): 35-45. https://doi.org/10.1016/j.mce.2013.07.010; PMid:23886990

Lago P. (2010). Premedication for non emergency intubation in the neonate. Minerva Pediatr. 62(3): 61-63.

Lee JY, Song H, Dash O, Park M, Shin NE, McLane MW et al. (2019). Administration of melatonin for prevention of preterm birth and fetal brain injury associated with premature birth in a mouse model. Am. J. Reprod. Immunol. 82(3): e13151. https://doi.org/10.1111/aji.13151; PMid:31131935

Maitra SK, Chattoraj A, Mukherjee S. (2013). Melatonin: a potent candidate in the regulation of fish oocyte growth and maturation. Gen. Comp. Endocrinol. 181: 215-222. https://doi.org/10.1016/j.ygcen.2012.09.015; PMid:23046602

Mark PJ, Crew RC, Wharfe MD, Waddell BJ. (2017). Rhythmic three-part harmony: the complex interaction of maternal, placental and fetal circadian systems. J. Biol. Rhythms. 32(6): 534-49. https://doi.org/10.1177/0748730417728671; PMid:28920512

Marseglia L, D'Angelo G, Manti S, Arrigo T, Barberi I, Reiter RJ et al. (2014). Oxidative stress-mediated aging during the fetal and perinatal periods. Oxid. Med. Cell. Longev. 2014: 358375. https://doi.org/10.1155/2014/358375; PMid:25202436 PMCid:PMC4151547

Mendez N, Abarzua-Catalan L, Vilches N. (2012). Timed Maternal Melatonin Treatment Reverses Circadian Disruption of the Fetal Adrenal Clock Imposed by Exposure to Constant Light. PLoS One. 7(8): e42713. https://doi.org/10.1371/journal.pone.0042713; PMid:22912724 PMCid:PMC3418288

Milczarek R, Hallmann A, Sokołowska E, Kaletha K, Klimek J. (2010). Melatonin enhances antioxidant action of α-tocopherol and ascorbate against NADPH- and iron-dependent lipid peroxidation in human placental mitochondria. J. Pineal. Res. 49(2): 149-155. https://doi.org/10.1111/j.1600-079X.2010.00779.x; PMid:20524970

Moore TA, Ahmad IM, Zimmerman MC. (2018). Oxidative stress and preterm birth: an integrative review. Biol. Res. Nurs. 20(5):497-512. https://doi.org/10.1177/1099800418791028

Mowafi HA, Ismail SA. (2008). Melatonin improves to urniquet tolerance an denhances postoperative an algesia in patient sreceiving intravenous regional anesthesia. Melatonin: a potent candidate in the regulation of fish oocyte growth and maturation. Anesth. Analg. 107(4): 1422-1426. https://doi.org/10.1213/ane.0b013e318181f689; PMid:18806063

Myatt L, Cui X. (2004). Oxidative stress in the placenta. Histochem. Cell. Biol. 122(4): 369-382. https://doi.org/10.1007/s00418-004-0677-x; PMid:15248072

Nakamura Y, Tamura H, Kashida S, Takayama H, Yamagata Y, Karube A et al. (2001, Jan). Changes of serum melatonin level and its relationship to feto-placental unit during pregnancy. J. Pineal. Res. 30(1): 29-33. https://doi.org/10.1034/j.1600-079X.2001.300104.x; PMid:11168904

Nakamura Y, Tamura H, Takayama H, Kato H. (2003). Increased endogenous level of melatonin in preovulatory human follicle does not directly influence progesterone production. Fertil. Steril. 80: 1012-1016. https://doi.org/10.1016/S0015-0282(03)01008-2; PMid:14556825

Olcese J, Lozier S, Paradise C. (2013). Melatonin and the circadian timing of human parturition Reprod. Sci. 20(2): 168-174. https://doi.org/10.1177/1933719112442244; PMid:22556015

Okatani Y, Okamoto K, Hayashi K. (2008). Maternal-fetal transfer of melatonin in pregnant women near term. J. Pineal. Res. 25: 129-134. https://doi.org/10.1111/j.1600-079X.1998.tb00550.x; PMid:9745980

Opie LH, Lecour S. (2016). Melatonin has multiorgan effects. Euro. Heart J. Cardiovasc. Pharmacother. 2: 258-265. https://doi.org/10.1093/ehjcvp/pvv037; PMid:27533945

Pierpaoli W. (1998). Neuroimmunomodulation of aging. A program in the pineal gland. Ann. NY Acad. Sci. 840: 491-497. https://doi.org/10.1111/j.1749-6632.1998.tb09587.x; PMid:9629275

Pfeffer M, Rauch A, Korf HW. (2012). The endogenous melatonin (MT) signal facilitates reentrainment of the circadian system to light-induced phase advances by acting upon MT2 receptors. Chronobiol. Int. 29(4): 415-429. https://doi.org/10.3109/07420528.2012.667859; PMid:22489607

Reiter RJ, Tan DX, Manchester LC, Paredes SD, Mayo JC, Sainz RM. (2009). Melatonin and reproduction revisited. Biol. Reprod. 81(3): 445-456. https://doi.org/10.1095/biolreprod.108.075655; PMid:19439728

Reiter RJ. (2013). The universal nature, unequal distribution and antioxidant functions of melatonin and its derivatives. Mini-reviews in Medicinal Chemistry. 13(3): 373-384. https://doi.org/10.2174/138955713804999810

Reiter RJ, Tan DX, Korkmaz A, Rosales-Corral SA. (2014). Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology. Hum. Reprod. Update. 20(2): 293-307. https://doi.org/10.1093/humupd/dmt054; PMid:24132226

Reschke L, McCarthy R, Herzog ED, Fay JC, Jungheim ES, England SK. (2018). Chronodisruption: An untimely cause of preterm birth? Best Pract. Res. Clin. Obstet. Gynaecol. 52: 60-67. https://doi.org/10.1016/j.bpobgyn.2018.08.001; PMid:30228028

Sandyk R, Tsagas N, Anninos PA. (1992, Mar). Melatonin as a proconvulsive hormone in humans. Int. J. Neurosci. 63(1-2): 125-135. https://doi.org/10.3109/00207459208986662; PMid:1342024

Sakaguchi K, Itoh MT, Takahashi N, Tarumi W, Ishizuka B. (2013). The rat oocyte synthesises melatonin Reproduction, Fertility and Development 25(4): 674-682. https://doi.org/10.1071/RD12091; PMid:22951050

Sagrillo-Fagundes L, Soliman A, Vaillancourt C. (2014). Maternal and placental melatonin: actions and implication for successful pregnancies. Minerva Ginecol. 66(3): 251-266.

Sagrillo-Fagundes L, Clabault H, Laurent L, Hudon-Thibeault AA, Salustiano EM, Fortier M et al. (2016). Human primary trophoblast cell culture model to study the protective effects of melatonin against hypoxia/reoxygenation-induced disruption. J. Vis. Exp. 113: 54228. https://doi.org/10.3791/54228; PMid:27500522 PMCid:PMC5091709

Sati L. (2020). Chronodisruption: effects on reproduction, transgenerational health of offspring and epigenome. Reproduction. 160(5): 79-94. https://doi.org/10.1530/REP-20-0298; PMid:33065548

Seron-Ferre M, Valenzuela GJ, Torres-Farfan C. (2007). Circadian clocks during embryonic and fetal development. Birth Defects Res C Embryo Today. 81(3): 204-214. https://doi.org/10.1002/bdrc.20101; PMid:17963275

Sharkey J, Cable C, Olcese J. (2010). Melatonin sensitizes human myometrial cells to oxytocin in a PKCα/ERK-dependent manner. J Clin. Endocrinol. Metab. 95(6): 2902-2908. https://doi.org/10.1210/jc.2009-2137; PMid:20382690 PMCid:PMC2902072

Schibler U. (2005). The daily rhythms of genes, cells and organs. Biological clocks and circadian timing in cells. EMBO Rep. 6(1): 9-13. https://doi.org/10.1038/sj.embor.7400424; PMid:15995671 PMCid:PMC1369272

Soliman A, Lacasse AA, Lanoix D, Sagrillo-Fagundes L, Boulard V, Vaillancourt C. (2015). Placental melatonin system is present throughout pregnancy and regulates villous trophoblast differentiation. J. Pineal. Res. 59(1): 38-46. https://doi.org/10.1111/jpi.12236; PMid:25833399

Slominski RM, Reiter RJ, Schlabritz-Loutsevitch N, Ostrom RS, Slominski AT. (2012). Melatonin membrane receptors in peripheral tissues: distribution and functions. Mol. Cell. Endocrinol. 351(2): 152-166. https://doi.org/10.1016/j.mce.2012.01.004; PMid:22245784 PMCid:PMC3288509

Schoots MH, Gordijn SJ, Scherjon SA, van Goor H, Hillebrands JL. (2018). Oxidative stress in placental pathology. Placenta. 69: 153-161. https://doi.org/10.1016/j.placenta.2018.03.003; PMid:29622278

Srinivasan V, Lauterbach EC, Ho KY. (2012). Melatonin in antinociception: its therapeutic applications. Curr. Neuropharmacol. 10(2): 167-178. https://doi.org/10.2174/157015912800604489; PMid:23204986 PMCid:PMC3386506

Su LJ, Zhang JH, Gomez H, Murugan R, Hong X, Xu D et al. (2019). Reactive oxygen species-induced lipid peroxidation in apoptosis, autophagy, and ferroptosis. Oxid. Med. Cell. Longev. 2019: 5080843. https://doi.org/10.1155/2019/5080843; PMid:31737171 PMCid:PMC6815535

Taggart MJ, Mowafi HA, Ismail SA, Arthur P, Zielnik B. (2012). Molecular pathways regulating contractility in rat uterus through late gestation and parturition. Am. J. Obstet. Gynecol. 207(1): 15-24. https://doi.org/10.1016/j.ajog.2012.04.036; PMid:22727353

Tan DX, Manchester LC, Hardeland R, Lopez-Burillo S, Mayo JC, Sainz RM et al. (2003). Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin. J. Pineal. Res. 34: 75-78. https://doi.org/10.1034/j.1600-079X.2003.02111.x; PMid:12485375

Tan DX, Manchester LC, Terron MP, Flores LJ, Reiter RJ. (2007). One molecule, many derivatives: A never-ending interaction of melatonin with reactive oxygen and nitrogen species? J. Pineal. Res. 42: 28-42. https://doi.org/10.1111/j.1600-079X.2006.00407.x; PMid:17198536

Tamura H, Nakamura Y, Terron MP, Flores LJ, Manchester LC, Tan DX et al. (2008). Melatonin and pregnancy in the human. Reprod. Toxicol. 25(3): 291-303. https://doi.org/10.1016/j.reprotox.2008.03.005; PMid:18485664

Tamura H, Takasaki A, Taketani T. (2013). Melatonin as a free radical scavenger in the ovarian follicle. Endocr. J. 60(1): 1-13. https://doi.org/10.1507/endocrj.EJ12-0263; PMid:23171705

Tamura H, Takasaki A, Taketani T, Tanabe M, Lee L, Tamura I et al. (2014). Melatonin and female reproduction. J. Obstet. Gynaecol. Res. 40(1): 1-11. https://doi.org/10.1111/jog.12177; PMid:24118696

Tarocco A, Caroccia N, Morciano G, Wieckowski MR, Ancora G, Garani G et al. (2019). Melatonin as a master regulator of cell death and inflammation: molecular mechanisms and clinical implications for newborn care. Cell. Death. Dis. 10(4): 317. https://doi.org/10.1038/s41419-019-1556-7; PMid:30962427 PMCid:PMC6453953

Thomas L, Purvis CC, Drew JE. (2002). Melatonin receptors in human fetal brain: 2-[(125)I] iodomelatonin binding and MT1 gene expression. J. Pineal. Res. 33(4): 218-224. https://doi.org/10.1034/j.1600-079X.2002.02921.x; PMid:12390504

Turco MY, Moffett A. (2019). Development of the human placenta. Development. 146(22). https://doi.org/10.1242/dev.163428; PMid:31776138

Tyana TJ, Schuch V, Hossack DJ, Chakraborty R, Johnson EL. (2024). Melatonin: the placental antioxidant and anti-inflammatory. Front. Immunol. 15: 1339304. https://doi.org/10.3389/fimmu.2024.1339304; PMid:38361952 PMCid:PMC10867115

Valenzuela FJ, Vera J, Venegas C, Pino F, Lagunas C. (2015). Circadian system and melatonin hormone: risk factors for complications during pregnancy. Obstet. Gynecol. Int. 2015: 825802. https://doi.org/10.1155/2015/825802; PMid:25821470 PMCid:PMC4363680

Vatish M, Steer PJ, Blanks AM, Hon M, Thornton S. (2010). Diurnal variation is lost in preterm deliveries before 28 weeks of gestation. Br J Obstet Gynecol. 117(6): 765-767. https://doi.org/10.1111/j.1471-0528.2010.02526.x; PMid:20236106

Venegas C, García JA, Escames G, Ortiz F, López A, Doerrier C et al. (2012). Extrapineal melatonin: analysis of its subcellular distribution and daily fluctuations. J. Pineal. Res. 52: 217-227. https://doi.org/10.1111/j.1600-079X.2011.00931.x; PMid:21884551

Vollrath L, Semm P, Gammel G. (1981). Sleep Induction by Intranasal Application of Melatonin. Melatonin: Current Status and Perspectives. Proceedings of an International Symposium on Melatonin, Held in Bremen, Federal Republic of Germany, September 28-30, 1980: 327-329. https://doi.org/10.1016/B978-0-08-026400-4.50043-8

Voiculescu SE, Zygouropoulos N, Zahiu CD, Zagrean AM. (2014). Role of melatonin in embryo fetal development. J. Med. Life 7(4):488-92.

Vriend J, Reiter RJ. (2015). Melatonin feedback on clock genes: a theory involving the proteasome. J. Pineal. Res. 58(1): 1-11. https://doi.org/10.1111/jpi.12189; PMid:25369242

Wilhelmsen M, Amirian I, Reiter RJ, Rosenberg J, Gogenur I. (2011). Analgesic effects of melatonin: a review of current evidence fromexperimental and clinical studies. J. Pineal. Res. 51: 270-277. https://doi.org/10.1111/j.1600-079X.2011.00895.x; PMid:21615490

Wu F, Tian FJ, Lin Y. (2015). Oxidative stress in placenta: health and diseases. BioMed. Res. Int. 2015: 293271. https://doi.org/10.1155/2015/293271; PMid:26693479 PMCid:PMC4676991

Wu F, Tian FJ, Lin Y, Xu WM. (2016). Oxidative stress: placenta function and dysfunction. Am. J. Reprod. Immunol. 76(4): 258-271. https://doi.org/10.1111/aji.12454; PMid:26589876

Zawilska JB, Skene DJ, Arendt J. (2009). Physiology and pharmacology of melatonin in relation to biological rhythms. Pharmacol. Rep. 61: 383-410. https://doi.org/10.1016/S1734-1140(09)70081-7; PMid:19605939

Published

2025-03-05