Melatonin in the pathogenesis of preeclampsia
- Authors: Evsyukova I.I.1, Kvetnoy I.M.2,3
-
Affiliations:
- The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
- Saint-Petersburg State Research Institute of Phthisiopulmonology
- Saint-Petersburg State University
- Issue: Vol 71, No 3 (2022)
- Pages: 53-64
- Section: Reviews
- URL: https://journals.eco-vector.com/jowd/article/view/103863
- DOI: https://doi.org/10.17816/JOWD103863
- ID: 103863
Cite item
Abstract
The review presents the results of experimental studies that have revealed the molecular mechanisms underlying implantation and placentation controlled by cytokines, chemokines, adhesion molecules, hormones, as well as transcription and growth factors, and have indicated the key regulatory and protective role of melatonin. It has been shown that low production of the hormone and lack of its circadian rhythm underlie the disruption of endogenous antioxidant protection and contribute to oxidative stress leading to the development of preeclampsia. The necessity of using melatonin as a neuroimmunoendocrine marker of pathology is emphasized in this review article, which will allow for developing new approaches to its use for the prevention and treatment of preeclampsia, as well as its adverse consequences, such as obesity, type 2 diabetes mellitus, renal failure, and cardiovascular pathology.
Keywords
Full Text
About the authors
Inna I. Evsyukova
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: eevs@yandex.ru
ORCID iD: 0000-0003-4456-2198
SPIN-code: 4444-4567
Scopus Author ID: 520074
MD, Dr. Sci. (Med.), Professor
Russian Federation, 3 Mendeleevskaya Line, Saint Petersburg, 199034Igor M. Kvetnoy
Saint-Petersburg State Research Institute of Phthisiopulmonology; Saint-Petersburg State University
Author for correspondence.
Email: igor.kvetnoy@yandex.ru
ORCID iD: 0000-0001-7302-5581
ResearcherId: H-4882-2016
MD, PhD, DSci (Medicine),
Russian Federation, 3 Mendeleevskaya Line, Saint Petersburg, 199034; Saint PetersburgReferences
- Rana S, Lemoine E, Granger JP, Karumanchi SA. Preeclampsia: Pathophysiology, challenges, and perspectives. Circ Res. 2019;124(7):1094–1112. doi: 10.1161/CIRCRESAHA.118.313276
- Jenabi E, Afshari M, Khazaei S. The association between preeclampsia and the risk of metabolic syndrome after delivery: a meta-analysis. J Matern-Fetal Neonat Med. 2021;34(19):3253−3258. doi: 10.1080/14767058.2019.1678138
- Armengaud JB, Yzydorczyk C, Siddeek B, et al. Intrauterine growth restriction: Clinical consequences on health and disease at adulthood. Reprod Toxicol. 2021;99:168−176. doi: 10.1016/j.reprotox.2020.10.005
- Garovic VD, White WM, Vaughan L, et al. Incidence and long-term outcomes of hypertensive disorders of pregnancy. J Am Coll Cardiol. 2020;75(18):2323−2334. doi: 10.1016/j.jacc.2020.03.028
- Abramova MY, Churnosov MI. Modern concepts of etiology, pathogenesis and risk factors for preeclampsia. Journal of Obstetrics and Women’s Diseases. 2021;70(5):105–116. doi: 10.17816/JOWD77046
- Bakrania BA, Spradley FT, Drummond HA, et al. Preeclampsia: Linking placental ischemia with maternal endothelial and vascular dysfunction. Compr Physiol. 2021;11(1):1315–1349. doi: 10.1002/cphy.c200008
- Lim S, Li W, Kemper J, et al. Biomarkers and the prediction of adverse outcomes in preeclampsia: A systematic review and meta-analysis. Obstet Gynecol. 2021;137(1):72–81. doi: 10.1097/AOG.0000000000004149
- Jena MK, Sharma NR, Petitt M, et al. Pathogenesis of preeclampsia and therapeutic approaches targeting the placenta. Biomolecules. 2020;10(6):953. doi: 10.3390/biom10060953
- Phipps EA, Thadhani R, Benzing T, Karumanchi SA. Pre-eclampsia: Pathogenesis, novel diagnostics and therapies. Nat Rev Nephrol. 2019;15:275−289. doi: 10.1038/s41581-019-0119-6
- Tamura H, Jozaki M, Tanabe M, et al. Importance of melatonin in assisted reproductive technology and ovarian aging. Int J Mol Sci. 2020;21(3):1135. doi: 10.3390/ijms21031135
- Ashary N, Tiwari A, Modi D. Embryo implantation: War in times of love. Endocrinology. 2018;159(2):1188−1198. doi: 10.1210/en.2017-03082
- Zhu YQ, Yan XY, Li H, Zhang C. Insights into the pathogenesis of preeclampsia based on the features of placentation and tumorigenesis. Reprod Dev Med. 2021;5:97−106. doi: 10.4103/2096-2924.320886
- Staff AC. The two-stage placental model of preeclampsia: An update. J Reprod Immunol. 2019;134−135:1–10. doi: 10.1016/j.jri.2019.07.004
- Hong K, Kim SH, Cha DH, Park HJ. Defective uteroplacental vascular remodeling in preeclampsia: Key molecular factors leading to long term cardiovascular disease. Int J Mol Sci. 2021;22(20):11202. doi: 10.3390/ijms222011202
- Chiarello DI, Abada C, Rojasa D, et al. Oxidative stress: Normal pregnancy versus preeclampsia. Biochim Biophys Acta Mol Basis Dis. 2020;1866(2):165354. doi: 10.1016/j.bbadis.2018.12.005
- Guerby P, Tasta O, Swiader A, et al. Role of oxidative stress in the dysfunction of the placental endothelial nitric oxide synthase in preeclampsia. Redox Biol. 2021;40:101861. doi: 10.1016/j.redox.2021.101861
- Zhou X, Han TL, Chen H, et al. Impaired mitochondrial fusion, autophagy, biogenesis and dysregulated lipid metabolism is associated with preeclampsia. Exp Cell Res. 2017;359(1):195–204. doi: 10.1016/j.yexcr.2017.07. 029
- Sutton EF, Gemmel M, Powers RW. Nitric oxide signaling in pregnancy and preeclampsia. Nitric Oxide. 2020,95:55–62. doi: 10.1016/j.niox.2019.11.006
- Hu X-Q, Zhang L. Hypoxia and mitochondrial dysfunction in pregnancy complications. Antioxidants (Basel). 2021;10(3):405. doi: 10.3390/antiox10030405
- Vangrieken P, Salwan Al-Nasiry S, Bast A, et al. Placental mitochondrial abnormalities in preeclampsia. Reprod Sci. 2021;28:2186–2199. doi: 10.1007/s43032-021-00464-y
- Stefańska K, Zieliński M, Jankowiak M, et al. Cytokine imprint in preeclampsia. Front Immunol. 2021;12:667841. doi: 10.3389/fimmu.2021.667841
- Nath MC, Cubro H, McCormick D.J, et al. Preeclamptic women have decreased circulating IL-10 (Interleukin-10) values at the time of preeclampsia diagnosis: systematic review and meta-analysis. Hypertension. 2020;76(6):1817–1827. doi: 10.1161/HYPERTENSIONAHA.120.15870
- Magatti M, Masserdotti A, Cargnoni A, et al. The role of B cells in PE pathophysiology: A potential target for perinatal cell-based therapy? Int J Mol Sci. 2021;22:3405. doi: 10.3390/ijms22073405
- Guney G, Taskin MI, Tokmak A. Increase of circulating inflammatory molecules in preeclampsia, an update. Eur Cytokine Netw. 2020;31(1):18−31. doi: 10.1684/ecn.2020.0443
- Sahu MB, Deepak V, Gonzale SK, et al. Decidual cells from women with preeclampsia exhibit inadequate decidualization and reduced sFlt1 suppression. Pregnancy Hypertens. 2018;15:64–71. doi: 10.1016/j.preghy.2018.11.003
- Huppertz B. Biology of preeclampsia: Combined actions of angiogenic factors, their receptors and placental proteins. Biochim Biophys Acta Mol Basis Dis. 2020;1866(2):165349. doi: 10.1016/j.bbadis.2018.11.024
- Nuh AM, You Y, Ma M. Information on dysregulation of microRNA in placenta. linked to preeclampsia. Bioinformation. 2021;17(1):240−248. doi: 10.6026/97320630017240
- Xu P, Ma Y, Wu H, Wang Y-L. Placenta-derived microRNAs in the pathophysiology of human pregnancy. Front Cell Dev Biol. 2021;9:646326 doi: 10.3389/fcell.2021.646326
- Sun N, Qin S, Zhang L, Shiguo S. Roles of noncoding RNAs in preeclampsia. Reprod Biol Endocrinol. 2021;19:100. doi: 10.1186/s12958-021-00783-4
- Wang Z, Yang R, Zhang J, et al. Role of extracellular vesicles in placental inflammation and local immune balance. Мediators inflamm. 2021:5558048. doi: 10.1155/2021/5558048
- Chuffa LGA, Lupi LA, Cucielo MS, et al. Melatonin promotes uterine and placental health: Potential molecular mechanisms. Int J Mol Sci. 2020;21(1):300. doi: 10.3390/ijms21010300
- Langston-Cox A, Marshall SA, Lu D, et al. Melatonin for the Management of Preeclampsia: A Review. Antioxidants (Basel). 2021;10(3):376. doi: 10.3390/antiox10030376
- Carlomagno G, Minini M, Tilotta M, Unfer V. From implantation to birth: Insight into molecular melatonin functions. Int J Mol Sci. 2018;19(9):2802. doi: 10.3390/ijms19092802
- Hannan NJ, Binder NK, Beard S, et al. 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. 2018;13(4):e0187082. doi: 10.1371/journal.pone.0187082
- Ramiro-Cortijo D, de la Calle M, Benitez V, et al. Maternal psychological and biological factors associated to gestational complications. J Pers Med. 2021;11(3):183. doi: 10.3390/jpm11030183
- Ferlazzo N, Andolina G, Cannata A, et al. Is melatonin the cornucopia of the 21st century? Antioxidants. 2020;9(11):1088. doi: 10.3390/antiox9111088
- Slominski RM, Reiter RJ, Schlabritz-Loutsevitch N, et al. Melatonin membrane receptors in peripheral tissues: Distribution and functions. Mol Cell Endocrinol. 2012;351(2):152–166. doi: 10.1016/j.mce.2012.01.004
- Kvetnoy I, Ivanov D, Mironova E., et al. Melatonin as the cornerstone of neuroimmunoendocrinology. Int J Mol Sci. 2022;23:1835. DOI: 10.3390/ ijms23031835
- Yu K, Wang RX, Li MH, et al. Melatonin reduces androgen production and upregulates hem oxygenase-1 expression in granulosa cells from PCOS patients with hypoestrogenia and hyperandrogenia. Oxid Med Cell Longev. 2019:8218650. doi: 10.1155/2019/8218650
- Guo Y, Sun TC, Wang HP, Chen X. Research progress of melatonin (MT) in improving ovarian function: A review of the current status. Aging (Albany NY). 2021;13(13):17930−17947. doi: 10.18632/aging.203231
- Olcese JM. Melatonin and female reproduction: An expanding universe. Front Endocrinol (Lausanne). 2020;11:85. doi: 10.3389/fendo.2020.0008511:85
- Rai S, Ghosh H. Modulation of human ovarian function by melatonin. Front Biosci (Elite Ed). 2021;13:140–157. doi: 10.2741/875
- Russo M, Forte G, Montanino Oliva M, et al. Melatonin and myo-inositol: Supporting reproduction from the oocyte to birth. Int J Mol Sci. 2021;22(16):8433. doi: 10.3390/ijms22168433
- Zhang S, Lin H, Kong S, et al. Physiological and molecular determinants of embryo implantation. Mol Aspects Med. 2013;34(5);939–980. doi: 10.1016/j.mam.2012.12.011
- He C, Wang J, Li Y, et al. Melatonin-related genes expressed in the mouse uterus during early gestation promote embryo implantation. J Pineal Res. 2015;58(3):300–309. doi: 10.1111/jpi.12216
- Cha J, Sun X, Dey SK. Mechanisms of implantation: strategies for successful pregnancy. Nat Med. 2012;18(12):1754–1767. DOI: 1038/nm.3012
- Bae H, Yang C, Lee J-Y, et al. Melatonin improves uterine-conceptus interaction via regulation of SIRT1 during early pregnancy. J Pineal Res. 2020;69(2):e12670. doi: 10.1111/jpi.12670
- Lanoix D, Beghdadi H, Lafond J, Vaillancourt C. Human placental trophoblasts synthesize melatonin and express its receptors. J Pineal Res. 2008;45(1):50–60. doi: 10.1111/j.1600-079X.2008.00555.x
- Swarnakar S, Paul S, Singh LP, Reiter RJ. Matrix metalloproteinases in health and disease: regulation by Melatonin. J Pineal Res. 2011;50(1):8–20. doi: 10.1111/j.1600-079X.2010.00812.x
- Mirza-Aghazadeh-Attari M, Reiter RJ, Rikhtegar R, et al. Melatonin: An atypical hormone with major functions in the regulation of angiogenesis. IUBMB Life. 2020;72(8):1560–1584. doi: 10.1002/iub.2287
- Uzun М, Gencer M, Turkon H, et al. Effects of melatonin on blood pressure, oxidative stress and placental expressions of TNFa, IL-6, VEGF and sFlt-1 in RUPP rat model of preeclampsiа. Arch Med Res. 2017;48(7):592−598. doi: 10.1016/j.arcmed.2017.08.007
- Waddel BJ, Wharfe MD, Crew RC, Mark PJ. A rhythmic placenta? Circadian variation, clock genes and placental function. Placenta. 2012;33(7):533–539. doi: 10.1016/j.placenta.2012.03.008
- Chitimus DM, Popescu MR, Voiculescu SE, et al. Melatonin’s impact on antioxidative and anti-inflammatory reprogramming in homeostasis and disease. Biomolecules. 2020;10(9):1211. doi: 10.3390/biom10091211
- Sagrillo-Fagundes L, Salustiano EMA, Ruano R, et al. Melatonin modulates autophagy and inflammation protecting human placental trophoblast from hypoxia/reoxygenation. J Pieal Res. 2018;65(4):e12520. doi: 10.1111/jpi.12520
- Ejaz H, Figaro JK, Woolner AMF, et al. Maternal serum melatonin increases during pregnancy and falls immediately after delivery implicating the placenta as a major source of melatonin. Front Endocrinol. 2021;11:623038. doi: 10.3389/fendo.2020.623038
- Majidinia M, Sadeghpour A, Mehrzadi S, et al. Melatonin: A pleiotropic molecule that modulates DNA damage response and repair pathways. J Pineal Res. 2017;63(1):e12416. doi: 10.1111/jpi.12416
- Tang Y, Groom K, Chamley L, Chen Q. Melatonin, a potential therapeutic agent for preeclampsia, reduces the extrusion of toxic extracellular vesicles from preeclamptic placenta. Cells. 2021;10(8):1904. doi: 10.3390/cells10081904
- Reiter RJ, Ma O, Sharm R. Melatonin in mitochondria: Mitigating clear and present dangers. Physiology. 2020;35(2):86–95. doi: 10.1152/physiol.00034.2019
- Carrascal L, Nunez-Abades P, Ayala A, Cano M. Role of melatonin in the inflammatory process and its therapeutic potential. Curr Pharm Des. 2018;24(14):1563–1588. doi: 10.2174/1381612824666180426112832
- Ren W, Liu G, Chen S, et al. Melatonin signaling in T cells: Functions and applications. J Pineal Res. 2017:62(3). doi: 10.1111/jpi.12394
- Kopustinskiene DM, Bernatoniene J. Molecular mechanisms of melatonin-mediated cell protection and signaling in health and disease. Pharmaceutics. 2021;13(2):129. doi: 10.3390/pharmaceutics13020129
- Pan X, Taylor MJ, Cohen E, et al. Circadian clock, time-restricted feeding and reproduction. Int J Mol Sci. 2020;21(3):831. doi: 10.3390/ijms21030831
- McCarthy R, Jungheim ES, Fay JC, et al. Riding the rhythm of melatonin through pregnancy to deliver on time. Front Endocrinol (Lausanne). 2019;10:616. doi: 10.3389/fendo.2019.00616
- Evsyukova II. The role of melatonin in prenatal ontogenesis. J Evol Biochim Physiol. 2021,57(1):33−43. doi: 10.31857/S0044452921010022
- Dou Y, Lin B, Cheng H, et al. The reduction of melatonin levels is associated with the development of preeclampsia: A meta-analysis. Hypertens Pregnancy. 2019;38(2):65−72. doi: 10.1080/10641955.2019.1581215
- Zeng K, Gao Y, Wan J, et al. The reduction in circulating levels of melatonin may be associated with the development of preeclampsia. J Hum Hypertens. 2016;30(11):666–671. doi: 10.1038/jhh.2016.37
- Bouchlariotou S, Liakopoulos V, Giannopoulou M, et al. Melatonin secretion is impaired in women with preeclampsia and an abnormal circadian blood pressure rhythm. Ren Fail. 2014;36(7):1001−1007. doi: 10.3109/0886022X.2014.926216
- Laste G, Silva AA, Gheno BR, Rychcik PM. Relationship between melatonin and high-risk pregnancy: A review of investigations published between the years 2010 and 2020. Chronobiol. 2021;38(2):168−181. doi: 10.1080/07420528.2020.1863975
- Berbets AM, Davydenko IS, Barbe AM, et al. Melatonin 1A and 1B receptors’ expression decreases in the placenta of women with fetal growth restriction. Reprod Sci. 2021;28(1):197−206. doi: 10.1007/s43032-020-00285-5
- Forrestel AC, Miedlich SU, Yurcheshen M, et al. Chronomedicine and type 2 diabetes: shining some light on melatonin. Diabetologia. 2017;60(5):808−822. doi: 10.1007/s00125-016-4175-1
- Nechme PA, Amaral FG, Middleton B, et al. Melatonin profiles during the third trimester of pregnancy and health status in the offspring among day and night workers: A case series. Neurobiol Sleep Circadian Rhythms. 2019;6:70−76. doi: 10.1016/j.nbscr.2019.04.001
- Palmer KR, Mockler JC, Davies-Tuck ML, et al. Protect-me: A parallel-group, triple blinded, placebo-controlled randomised clinical trial protocol assessing antenatal maternal melatonin supplementation for fetal neuroprotection in early-onset fetal growth restriction. BMJ Open. 2019;9(6):e028243. doi: 10.1136/bmjopen-2018-028243
- Fernando S, Wallace EM, Vollenhoven B, et al. Melatonin in assisted reproductive technology: A pilot double-blind randomized placebo-controlled clinical trial. Front Endocrino (Lausanne). 2018;9:545. doi: 10.3389/fendo.2018.00545
- Khezri MB, Reihany MD, Dabbaghi Ghaleh T, Mohammadi N. Effect of melatonin on blood loss after cesarean section: A prospective randomized double-blind trial. J Obstet. Gynaecol India. 2019;69(5):436–443. doi: 10.1007/s13224-019-01205-7
- Hobson SR, Gurusinghe S, Lim R, et al. Melatonin improves endothelial function in vitro and prolongs pregnancy in women with early-onset preeclampsia. J Pineal Res. 2018;65(3):e12508. doi: 10.1111/jpi.12508
- Zheng M, Tong J, Li WP, Chen ZJ, Zhang C. 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. Gynecol Endocrinol. 2018;34(5):446–450. doi: 10.1080/09513590.2017.1409713
- Mokhtari F, Akbari Asbagh F, Azmoodeh O, et al. Effects of melatonin administration on chemical pregnancy rates of polycystic ovary syndrome patients undergoing intrauterine insemination: A randomized clinical trial. Int J Fertil Steril. 2019;13(3):225–229. doi: 10.22074/ijfs.2019.5717
- Valenzuela-Melgarejo FJ, Lagunas C, Carmona-Pastén F, et al. Supraphysiological role of melatonin over vascular dysfunction of pregnancy, a new therapeutic agent? Front Physiol. 2021;12:767684. doi: 10.3389/fphys.2021.767684
- De Martelly VA, Dreixler J, Tung A, et al Long-term postpartum cardiac function and its association with preeclampsia. J Am Heart Assoc. 2021;10(5):e018526. doi: 10.1161/JAHA.120.018526