Melatonin, placental growth factor and placental hormones at placental insufficiency

Cell and Organ Transplantology. 2019; 7(2):103-107.
DOI: 10.22494/cot.v7i2.100

Melatonin, placental growth factor and placental hormones at placental insufficiency

Berbets A.¹, Konkov D.², Bulavenko O.², Taran O.², Bakun O.¹¹Bukovinian State Medical University, Chernivtsi, Ukraine
²National Pirogov Memorial Medical University, Vinnytsya, Ukraine

Abstract
A pineal gland attracts much attention of scientists lately, because it secrets melatonin, which is a very important hormone. Melatonin plays a significant role in the development of pregnancy: it enhances implantation, decreases oxidative stress etc. At the same time, the links between the pineal gland and the placenta, as a part of endocrine system of a mother, are still not well described.
Objective of the study. To investigate the pathogenic links between secretion of melatonin, placental growth factor and reproductive hormones in pregnant women with placental insufficiency, manifested as intrauterine fetal growth restriction.
Material and methods. 35 pregnant women aged 18-36 with placental insufficiency (PI) were examined (study group). The placental insufficiency manifested as the intrauterine fetal growth restriction (IUGR) in the 3^rd pregnancy trimester. The control group consisted of 20 women with uncomplicated pregnancy at the same term. The blood concentrations of melatonin and placental growth factor (PlGF) were studied, as well as the blood concentrations of certain placental hormones: progesterone, placental lactogen and unconjugated estriol.
Results. The concentration of melatonin was found to decrease significantly, if pregnancy was complicated by intrauterine fetal growth retardation (study group – 129.90 ± 17.65 pg/ml, control group – 231.25 ± 21.56 pg/ml, p < 0.01), as well as concentration of PlGF (study group – 130,78 ± 15,80 pg/ml, control group – 230.0 ± 29.97 pg/ml, p < 0.01). A significant difference of progesterone concentrations between the groups was found (study group: 15.36 ± 2.78 ng/ml, control group: 30.43 ± 2.66 ng/ml, p < 0.01), as well as for placental lactogen (study group: 6.31 ± 2.08 mg/l, control group: 7.76 ± 1.93 mg/l, p < 0.05). No significant difference between the concentrations of unconjugated estriol was found. A close correlation between melatonin and progesterone in the control group was found (r = 0.76, P = 0.0001), a moderate correlation between melatonin and unconjugated estriol was also established in the control group (r = 0.61, P = 0.004), and a moderate negative correlation between melatonin and placental lactogen was found in the study group (r = -0.438, P = 0.042).
Conclusions. The blood levels of melatonin and PlGF significantly decrease in case of placental insufficiency, manifested as intrauterine fetal growth restriction syndrome. In healthy pregnant women, the secretion of steroid hormones (progesterone and unconjugated estriol) by placenta directly correlates with blood concentration of melatonin. This link is being disordered in case of placental insufficiency.

Key words: placental insufficiency, melatonin, placental growth factor, progesterone, placental lactogen, unconjugated estriol

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References

1. Grishchenko VI. Rol’ epifiza v fiziologii i patologii zhenskoy polovoy sistemy [Role of a pineal gland in physiology and pathology of woman’s reproductive system]. Khar’kov: Vishcha shkola; 1979. 248 s. [in Russian].

2. Shimada M, Seki H, Samejima M, Hayase M, Shirai F. Salivary melatonin levels and sleep-wake rhythms in pregnant women with hypertensive and glucose metabolic disorders: A prospective analysis. BioSci Trends. 2016; 10(1):34-41. DOI: 10.5582/bst.2015.01123. https://doi.org/10.5582/bst.2015.01123 PMid:26853813

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

4. Takayama H, Nakamura Y, Tamura H. Pineal gland (melatonin) affects the parturition time but not luteal function and fetal growth, in pregnant rats. Endocr J. 2003; 50(1):37-43. DOI: 10.1507/endocrj.50.37. https://doi.org/10.1507/endocrj.50.37 PMid:12733707

5. Teixeira AA, Simoes MJ, Wanderley Teixeira V, Soares JJr. Evaluation of the implantation in pinealectomized and/or submitted to the constant illumination rats. Int J Morphol. 2004; 22(3):189-194. https://doi.org/10.4067/S0717-95022004000300003

6. Richter HG, Hansell JA, Raut Sh, Giussani DA. Melatonin improves placental efficiency and birth weight and increases the placental expression of antioxidant enzymes in undernourished pregnancy. J Pineal Res. 2009; 46:357-364. DOI: 10.1111/j.1600-079X.2009.00671.x. https://doi.org/10.1111/j.1600-079X.2009.00671.x PMid:19552758

7. Reiter RJ, Dun Xian Tan, Korkmaz A, Rosales-Corral SA. Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology. Hum Reprod Update. 2013; 20(2):293-307. DOI: 10.1093/humupd/dmt054. https://doi.org/10.1093/humupd/dmt054 PMid:24132226

8. Marseglia L, D’Angelo G, Manti S, Reiter RJ, Gitto E. Potential Utility of melatonin in preeclampsia, intrauterine fetal growth retardation, and perinatal asphyxia. Reprod Sci. 2016; 23(8):970-977. DOI: 10.1177/1933719115612132. https://doi.org/10.1177/1933719115612132 PMid:26566856

9. Sun C, Yue J, He N, Liu Y, Zhang X, Zhang Y. Fundamental Principles of Stem Cell Banking. Adv Exp Med Biol. 2016; 951:31-45. DOI: 10.1007/978-3-319-45457-3_3. https://doi.org/10.1007/978-3-319-45457-3_3 PMid:27837552

10. Teofili L, Silini AR, Bianchi M, Valentini CG, Parolini O. Incorporating placental tissue in cord blood banking for stem cell transplantation. Expert Rev Hematol. 2018 Aug; 11(8):649-661. DOI: 10.1080/17474086.2018.1483717. https://doi.org/10.1080/17474086.2018.1483717 PMid:29856650

11. Albanna MZ, Woods EJ. Fetal Stem Cell Banking. Stem Cell Biology and Regenerative Medicine. 2016; 295-316. DOI: 10.1007/978-1-4939-3483-6_16. https://doi.org/10.1007/978-1-4939-3483-6_16

12. Xie Y, Zhou S, Jiang Z, Dai J, Puscheck EE, Lee I, et al. Hypoxic stress induces, but cannot sustain trophoblast stem cell differentiation to labyrinthine placenta due to mitochondrial insufficiency. Stem Cell Res. 2014; 13(3):478-91. DOI: 10.1016/j.scr.2014.07.007. https://doi.org/10.1016/j.scr.2014.07.007 PMid:25239494 PMCid:PMC4253717

13. Bentona S, McCowan L, Heazell A, et al. Placental growth factor as a marker of fetal growth restriction caused by placental dysfunction. Placenta. 2016; 42:1-8. DOI: 10.1016/j.placenta.2016.03.010. https://doi.org/10.1016/j.placenta.2016.03.010 PMid:27238707

14. Ong C, Liao A, Cacho A, et al. First-trimester maternal serum levels of placenta growth factor as predictor preeclampsia and fetal growth restriction. Am J Obstet Gynecol. 2001; 98(4):608-611. DOI: 10.1016/s0029-7844(01)01528-9. https://doi.org/10.1016/S0029-7844(01)01528-9

15. Bligh LN, Greer RM, Kumar S. The relationship between maternal placental growth factor levels and intrapartum fetal compromise. Placenta. 2016; 48:63-67. DOI: 10.1016/j.placenta.2016.10.007. https://doi.org/10.1016/j.placenta.2016.10.007 PMid:27871474

16. Kwiatkowski S, Kwiatkowska E, Rzepka R, Dołegowska B, Torbe A, Bartosik-Sławińska A. Using Doppler ultrasound of the uterine and umbilical arteries and disordered angiogenesis markers (sFlt-1/PlGF) in unified monitoring of ischemic placental syndrome patients. Hypertens Pregnancy. 2016; 35(4):490-498. DOI: 10.1080/10641955.2016.1186688. https://doi.org/10.1080/10641955.2016.1186688 PMid:27314436

17. Broere-Brown ZA, Schalekamp-Timmermans S, Jaddoe VWV, Steegers EAP. Fetal Growth and Placental Growth Factor Umbilical Cord Blood Levels. Fetal Diagn Ther. 2018; 43(1):26-33. DOI: 10.1159/000475547. https://doi.org/10.1159/000475547 PMid:28926825

18. Sherrell H, Dunn L, Clifton V, Kumar S. Systematic review of maternal Placental Growth Factor levels in late pregnancy as a predictor of adverse intrapartum and perinatal outcomes. Eur J Obstet Gynecol Reprod Biol. 2018; 225:26-34. DOI: 10.1016/j.ejogrb.2018.03.059. https://doi.org/10.1016/j.ejogrb.2018.03.059 PMid:29631209

19. Regnault TR, de Vrijer B, Galan HL, Davidsen ML, Trembler KA, Battaglia FC, et al. The relationship between transplacental O2 diffusion and placental expression of PlGF, VEGF and their receptors in a placental insufficiency model of fetal growth restriction. J Physiol. 2003; 15(550):641-56. DOI: 10.1113/jphysiol.2003.039511. https://doi.org/10.1113/jphysiol.2003.039511 PMid:12740423 PMCid:PMC2343042

20. González A, Martínez-Campa C, Alonso-González C, Cos S. Melatonin affects the dynamic steady-state equilibrium of estrogen sulfates in human umbilical vein endothelial cells by regulating the balance between estrogen sulfatase and sulfotransferase. Int J Mol Med. 2015; 36: 1671-1676. DOI: 10.3892/ijmm.2015.2360. https://doi.org/10.3892/ijmm.2015.2360 PMid:26458420

21. Taketani T, Tamura H, Takasaki A, Lee L, Kizuka F, Tamura I, et al. Protective role of melatonin in progesterone production by human luteal cells. J Pineal Res. 2011; 51:207-13. DOI: 10.1111/j.1600-079X.2011.00878.x. https://doi.org/10.1111/j.1600-079X.2011.00878.x PMid:21585519

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

23. 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. https://doi.org/10.3390/ijms19092802 PMid:30227688 PMCid:PMC6164374

24. Valenzuela FJ, Vera J, Venegas C, Pino F, Lagunas C. Circadian System and Melatonin Hormone: Risk Factors for Complications during Pregnancy. Obstet Gynecol Int. 2015; 2015: 825802. DOI: 10.1155/2015/825802. https://doi.org/10.1155/2015/825802 PMid:25821470 PMCid:PMC4363680

25. Hu C, Li L. Melatonin plays critical role in mesenchymal stem cell-based regenerative medicine in vitro and in vivo. Stem Cell Res Ther. 2019; 10:13. DOI: 10.1186/s13287-018-1114-8. https://doi.org/10.1186/s13287-018-1114-8 PMid:30635065 PMCid:PMC6329089

26. Dilogo IH, Fiolin, J, Aprianto P. Osteogenic Potency of Secretome Bone Marrow Derived Mesenchymal Stem Cells: A Literature Review. Adv Sci Let. 2018; 24(8): 6206-6208. DOI: 10.1166/asl.2018.12684. https://doi.org/10.1166/asl.2018.12684

How to cite

Berbets A, Konkov D, Bulavenko O, Taran O, Bakun O. Melatonin, placental growth factor and placental hormones at placental insufficiency. Cell and Organ Transplantology. 2019; 7(2):103-107. doi:10.22494/cot.v7i2.100

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