Email this article Expression of the serotonergic system components in the placenta in various types of preeclampsia
- Authors: Bettikher O.A.1,2, Belyaeva O.A.1, Dukovich A.I.1, Vorobeva O.M.1, Tral T.G.2, Tolibova G.K.2, Bart V.A.1, Kogan I.Y.1,2, Zazerskaya I.E.1,2
-
Affiliations:
- Almazov National Medical Research Centre
- The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
- Issue: Vol 72, No 1 (2023)
- Pages: 5-16
- Section: Original Research
- URL: https://journals.eco-vector.com/jowd/article/view/110890
- DOI: https://doi.org/10.17816/JOWD110890
- ID: 110890
Cite item
Open Access
Access granted
Abstract
BACKGROUND: The serotonergic system plays an important role in the formation and development of the feto-placental complex. The study of the expression of the serotonin system components, including placental 5-HT2A (serotonin receptor) and SERT (serotonin transporter), in preeclampsia will create prerequisites for discovering new ways to correct hypertensive pregnancy complications and methods of influencing pregnancy outcomes.
AIM: The aim of this study was to compare the expressions of 5-HT2A and SERT in placental tissue in pure preeclampsia and its combinations with other complications of pregnancy.
MATERIALS AND METHODS: A comparative cohort study was conducted among patients with different preeclampsia phenotypes: preeclampsia (n = 6), preeclampsia and gestational diabetes mellitus (n = 6), gestational diabetes mellitus and superimposed preeclampsia (preeclampsia + chronic arterial hypertension) (n = 6), and normal pregnancy without pregnancy complications (n = 6). The expression of 5-HT2A (Abcam, USA) and SERT (BiossAntibodies, USA) was studied in placenta samples from all study groups by immunohistochemical method. Morphometric analysis was performed using the VideoTest-Morphology 5.2 program (Videotest Ltd., Russia). The database was constructed and statistical processing was performed using Microsoft Excel 2007 (Microsoft Corporation, USA) and the StatTech program v. 2.6.4 (Stattech Ltd., Russia).
RESULTS: The expression of SERT and 5-HT2A is higher in the studied pregnancy complications when compared to the normal one. The relative 5-HT2A expression area in the placenta among the studied nosologies is higher in preeclampsia without gestational diabetes mellitus or in superimposed preeclampsia in combination with chronic arterial hypertension compared to expression in placentas in preeclampsia in combination with gestational diabetes mellitus or in preeclampsia in combination with gestational diabetes mellitus and chronic arterial hypertension (p = 0.02 and p = 0.017, respectively). The relative area of SERT expression is higher in preeclampsia without gestational diabetes mellitus or chronic arterial hypertension and in preeclampsia in combination with gestational diabetes mellitus compared to preeclampsia in combination with gestational diabetes mellitus and chronic arterial hypertension (p = 0.002 and p = 0.012, respectively).
CONCLUSIONS: The highest expressions of 5-HT2A and SERT among the studied preeclampsia phenotypes were found in placentas in preeclampsia without gestational diabetes mellitus or chronic arterial hypertension.
Keywords
Full Text
About the authors
Ofelia A. Bettikher
Almazov National Medical Research Centre; The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Author for correspondence.
Email: ophelia.bettikher@gmail.com
ORCID iD: 0000-0002-1161-1558
SPIN-code: 4398-3964
Scopus Author ID: 57190122861
ResearcherId: AAH-8832-2020
MD, Cand. Sci. (Med.)
Russian Federation, Saint Petersburg; Saint PetersburgOlga A. Belyaeva
Almazov National Medical Research Centre
Email: belyaevaolga0138@gmail.com
ORCID iD: 0000-0002-6970-7085
SPIN-code: 2229-5409
Russian Federation, Saint Petersburg
Albina I. Dukovich
Almazov National Medical Research Centre
Email: alyadukovich@gmail.com
ORCID iD: 0000-0002-7912-035X
Russian Federation, Saint Petersburg
Olga M. Vorobeva
Almazov National Medical Research Centre
Email: olgarasp@yandex.ru
ORCID iD: 0000-0002-1349-7349
SPIN-code: 3327-7617
Scopus Author ID: 57205331117
ResearcherId: AAZ-5818-2020
MD, Cand. Sci. (Med.)
Russian Federation, Saint PetersburgTatiana G. Tral
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: ttg.tral@yandex.ru
ORCID iD: 0000-0001-8948-4811
SPIN-code: 1244-9631
Scopus Author ID: 37666260400
MD, Cand. Sci. (Med.)
Russian Federation, Saint PetersburgGulrukhsor Kh. Tolibova
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: gulyatolibova@mail.ru
ORCID iD: 0000-0002-6216-6220
SPIN-code: 7544-4825
Scopus Author ID: 23111355700
ResearcherId: Y-6671-2018
MD, Dr. Sci. (Med.)
Russian Federation, Saint PetersburgViktor A. Bart
Almazov National Medical Research Centre
Email: vbartvit@mail.ru
ORCID iD: 0000-0002-9406-4421
SPIN-code: 9400-0754
Scopus Author ID: 8314645900
Cand. Sci. (Phys. & Math.)
Russian Federation, Saint PetersburgIgor Yu. Kogan
Almazov National Medical Research Centre; The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: ikogan@mail.ru
ORCID iD: 0000-0002-7351-6900
SPIN-code: 6572-6450
Scopus Author ID: 56895765600
ResearcherId: P-4357-2017
MD, Dr. Sci. (Med.), Professor, Corresponding Member of the Russian Academy of Sciences
Russian Federation, Saint Petersburg; Saint PetersburgIrina E. Zazerskaya
Almazov National Medical Research Centre; The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: zazera@mail.ru
ORCID iD: 0000-0003-4431-3917
SPIN-code: 5683-6741
Scopus Author ID: 55981393900
ResearcherId: AAI-1309-2020
MD, Dr. Sci. (Med.), Professor
Russian Federation, Saint Petersburg; Saint PetersburgReferences
- Valencia-Ortega J, Saucedo R, Sánchez-Rodríguez MA, et al. Epigenetic alterations related to gestational diabetes mellitus. Int J Mol Sci. 2021;22(17). doi: 10.3390/ijms22179462
- Watts SW. 5-HT in systemic hypertension: foe, friend or fantasy? Clinical Science. 2005;108(5):399–412. doi: 10.1042/cs20040364
- Hadden C, Fahmi T, Cooper A, et al. Serotonin transporter protects the placental cells against apoptosis in caspase 3-independent pathway. J Cell Physiol. 2017;232(12):3520–3529. doi: 10.1002/jcp.25812
- Bönisch H, Fink KB, Malinowska B, et al. Serotonin and beyond — a tribute to Manfred Göthert (1939-2019). Naunyn-Schmiedeberg’s Arch Pharmacol. 2021;394(9):1829–1867. doi: 10.1007/s00210-021-02083-5
- Athar S. Serotonin and tryptophan. In: Encyclopedia of movement disorders. Ed. by K. Kompoliti, L. Verhagen Metman. Amsterdam: Elsevier; 2010. P. 104–108. doi: 10.1016/b978-0-12-374105-9.00001-0
- Gumusoglu S, Scroggins S, Vignato J, et al. The serotonin-immune axis in preeclampsia. Curr Hypertens Rep. 2021;23(7):37. doi: 10.1007/s11906-021-01155-4
- Mercado CP, Kilic F. Molecular mechanisms of SERT in platelets: regulation of plasma serotonin levels. Molecular Interventions. 2010;10(4):231–241. doi: 10.1124/mi.10.4.6
- Ni W, Watts SW. 5-hydroxytryptamine in the cardiovascular system: focus on the serotonin transporter (SERT). Clin Exp Pharmacol Physiol. 2006;33(7):575–583. doi: 10.1111/j.1440-1681.2006.04410.x
- Fraer M, Kilic F. Serotonin: a different player in hypertension-associated thrombosis. Hypertension. 2015;65(5):942–948. doi: 10.1161/hypertensionaha.114.05061
- Iwabayashi M, Taniyama Y, Sanada F, et al. Role of serotonin in angiogenesis: Induction of angiogenesis by sarpogrelate via endothelial 5-HT1B/Akt/eNOS pathway in diabetic mice. Atherosclerosis. 2012;220(2):337–342. doi: 10.1016/j.atherosclerosis.2011.10.042
- Deroy K, Côté F, Fournier T, et al. Serotonin production by human and mouse trophoblast: involvement in placental development and function. Placenta. 2013;34(9). doi: 10.1016/j.placenta.2013.06.214
- Balsells M, García-Patterson A, Gich I, et al. Major congenital malformations in women with gestational diabetes mellitus: a systematic review and meta-analysis. Diabetes Metab Res Rev. 2012;28(3):252–257. doi: 10.1002/dmrr.1304
- Murthi P, Vaillancourt C. Placental serotonin systems in pregnancy metabolic complications associated with maternal obesity and gestational diabetes mellitus. Biochim Biophys Acta Mol Basis Dis. 2019;1866(2). doi: 10.1016/j.bbadis.2019.01.017
- Goeden N, Velasquez J, Arnold KA, et al. Maternal inflammation disrupts fetal neurodevelopment via increased placental output of serotonin to the fetal brain. J Neurosci. 2016;36(22):6041–6049. doi: 10.1523/JNEUROSCI.2534-15.2016
- Baković P, Kesić M, Perić M, et al. Differential serotonin uptake mechanisms at the human maternal-fetal interface. In J Mol Sci. 2021;22(15). doi: 10.3390/ijms22157807
- Ayme-Dietrich E, Aubertin-Kirch G, Maroteaux L, et al. Cardiovascular remodeling and the peripheral serotonergic system. Arch Cardiovasc Dis. 2017;110(1):51–59. doi: 10.1016/j.acvd.2016.08.002
- Staff AC, Johnsen GM, Dechend R, et al. Preeclampsia and uteroplacental acute atherosis: immune and inflammatory factors. J Reprod Immunol. 2014;101–102:120–126. doi: 10.1016/j.jri.2013.09.001
- Blazevic S, Horvaticek M, Kesic M, et al. Epigenetic adaptation of the placental serotonin transporter gene (SLC6A4) to gestational diabetes mellitus. Plos One. 2017;12(6). doi: 10.1371/journal.pone.0179934
- Bettikher OA, Zazerskaya IE, Popova PV, et al. Preeclampsia features in pregnancy with gestational diabetes mellitus. Journal of Obstetrics and Women’s Diseases. 2019;68(5):19–36. (In Russ.). doi: 10.17816/JOWD68519-36
- El-Tarhouny SA, Almasry SM, Elfayomy AK, et al. Placental growth factor and soluble Fms-like tyrosine kinase 1 in diabetic pregnancy: a possible relation to distal villous immaturity. Histol Histopathol. 2014;29(2):259–272. doi: 10.14670/HH-29.259
- Troncoso F, Acurio J, Herlitz K, et al. Gestational diabetes mellitus is associated with increased pro-migratory activation of vascular endothelial growth factor receptor 2 and reduced expression of vascular endothelial growth factor receptor 1. Plos One. 2017;12(8). doi: 10.1371/journal.pone.0182509
- Kapustin RV. Possibilities for prediction and prevention of preeclampsia in women with diabetes mellitus. Journal of Obstetrics and Women’s Diseases. 2018;67(3):20–29. (In Russ.). doi: 10.17816/JOWD67320-29
- Kapustin RV, Arzhanova ON, Polyakova VO. Vascular tropic signaling molecules expression in the placental tissue samples from puerperae with gestational diabetes mellitus. Molecular Medicine. 2012;(5):45–49. (In Russ.)
- Rosenfeld CS. Placental serotonin signaling, pregnancy outcomes, and regulation of fetal brain development. Biol Reprod. 2020;102(3):532–538. doi: 10.1093/biolre/ioz204
- Chanrion B, Mannoury la Cour C, Bertaso F, et al. Physical interaction between the serotonin transporter and neuronal nitric oxide synthase underlies reciprocal modulation of their activity. Proc Natl Acad Sci USA. 2007; 104(19):8119–8124. doi: 10.1073/pnas.0610964104
- Patrick Davis R, Linder AE, Watts SW. Lack of the serotonin transporter (SERT) reduces the ability of 5-hydroxytryptamine to lower blood pressure. Naunyn Schmiedebergs Arch Pharmacol. 2011;383(5):543–546. doi: 10.1007/s00210-011-0622-1
- Monassier L, Maroteaux L. Serotonin and cardiovascular diseases. In: Serotonin: The Mediator That Spans Evolution. Ed. by P.M. Pilowsky. Amsterdam: Elsevier; 2019. P. 203–238. doi: 10.1016/b978-0-12-800050-2.00012-7
- Aflyatumova GN, Nigmatullina RR, Sadykova DI, et al. Endothelin-1, nitric oxide, serotonin and high blood pressure in male adolescents. Vasc Health Risk Manag. 2018;14:213–223. doi: 10.2147/VHRM.S170317
- Iqbal M, Audette MC, Petropoulos S, et al. Placental drug transporters and their role in fetal protection. Placenta. 2012;33(3):137–142. doi: 10.1016/j.placenta.2012.01.008
Supplementary files
