Serotonin receptor and serotonin transporter expressions in the placental villous tree in gestational diabetes mellitus

Abstract

BACKGROUND: The serotonergic system during pregnancy plays an important role not only in carbohydrate metabolism, but also in the laying and regulation of the fetoplacental complex, growth and development of the fetus. The study of the expression of placental serotonin 5-HT2A receptor and serotonin transporter (SERT) in gestational diabetes mellitus is foremost for scrutinizing the pathogenesis of perinatal complications, as it may allow for finding new opportunities for their prevention and correction.

AIM: The aim of this study was to compare the expression patterns of the serotonin 5-HT2A receptor and SERT in placental tissue in gestational diabetes mellitus and in normal pregnancy.

MATERIALS AND METHODS: This comparative cohort study included pregnant women with gestational diabetes mellitus (n = 6) and patients with normal pregnancy (n = 10). The expression of serotonin 5-HT2A receptor (Abcam, USA) and SERT (Bioss Antibodies, USA) was studied in placenta samples from the both study groups by immunohistochemical method. Morphometric analysis was performed using the VideoTest-Morphology 5.2 program (Videotest Ltd., Russia).

RESULTS: The relative area of SERT expression in the placenta in gestational diabetes mellitus was higher compared to normal pregnancy (p < 0.001). The relative areas of expression of the serotonin 5-HT2A receptor in the placenta did not differ between the study groups (p = 0.5).

CONCLUSIONS: Higher SERT expression in the placentas of patients with gestational diabetes mellitus compared to those from women with normal pregnancies may reflect the level of tension of compensatory mechanisms in gestational diabetes mellitus and the effect of insulin therapy on these mechanisms.

Keywords

gestational diabetes mellitus / placenta / serotonin / 5-HT2A / SERT

References

[1] Watts SW. 5-HT in systemic hypertension: foe, friend or fantasy? Clin Sci (Lond). 2005;108(5):399–412. doi: 10.1042/CS20040364

[2] Watts S.W. 5-HT in systemic hypertension: foe, friend or fantasy? // Clin Sci (Lond). 2005. Vol. 108, N. 5. Р. 399–412. doi: 10.1042/CS20040364

[3] Kanova M, Kohout P. Serotonin-its synthesis and roles in the healthy and the critically ill. Int J Mol Sci. 2021;22(9):4837. doi: 10.3390/ijms22094837

[4] Kanova M., Kohout P. Serotonin — its synthesis and roles in the healthy and the critically ill. // Int J Mol. Sci. 2021. Vol 22, N. 9. P. 4837. doi: 10.3390/ijms22094837

[5] 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

[6] Deroy K., Côté F., Fournier T., et al. Serotonin production by human and mouse trophoblast: involvement in placental development and function // Placenta. 2013. Vol. 34, N. 9. P. A71. doi: 10.1016/j.placenta.2013.06.214

[7] 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. 2020;1866(2). doi: 10.1016/j.bbadis.2019.01.017

[8] 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. 2020. Vol. 1866, N. 2. doi: 10.1016/j.bbadis.2019.01.017

[9] 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

[10] 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. Vol. 232, N. 12. P. 3520–3529. doi: 10.1002/jcp.25812

[11] Viau M, Lafond J, Vaillancourt C. Expression of placental serotonin transporter and 5-HT 2A receptor in normal and gestational diabetes mellitus pregnancies. Reprod Biomed Online. 2009;19(2):207–215. doi: 10.1016/s1472-6483(10)60074-0

[12] Viau M., Lafond J., Vaillancourt C. Expression of placental serotonin transporter and 5-HT 2A receptor in normal and gestational diabetes mellitus pregnancies // Reprod Biomed Online. 2009. Vol. 19, N. 2. P. 207–215. doi: 10.1016/s1472-6483(10)60074-0

[13] 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

[14] Blazevic S., Horvaticek M., Kesic M., et al. Epigenetic adaptation of the placental serotonin transporter gene (SLC6A4) to gestational diabetes mellitus // PLoS One. 2017. Vol. 12, N. 6. doi: 10.1371/journal.pone.0179934

[15] Li Y, Hadden C, Singh P, et al. GDM-associated insulin deficiency hinders the dissociation of SERT from ERp44 and down-regulates placental 5-HT uptake. Proc Natl Acad Sci USA. 2014;111(52):E5697–E5705. doi: 10.1073/pnas.1416675112

[16] Li Y., Hadden C., Singh P., et al. GDM-associated insulin deficiency hinders the dissociation of SERT from ERp44 and down-regulates placental 5-HT uptake // Proc Natl Acad Sci USA. 2014. Vol. 111, N. 52. P. E5697–E5705. doi: 10.1073/pnas.1416675112

[17] Carrasco-Wong I, Moller A, Giachini FR, et al. Placental structure in gestational diabetes mellitus. Biochim Biophys Acta Mol Basis Dis. 2020;1866(2). doi: 10.1016/j.bbadis.2019.165535

[18] Carrasco-Wong I., Moller A., Giachini F.R., et al. Placental structure in gestational diabetes mellitus // Biochim Biophys Acta Mol Basis Dis. 2020. Vol. 1866, N. 2. doi: 10.1016/j.bbadis.2019.165535

[19] Tral TG, Tolibova GK, Musina EV, et al. Molecular and morphological peculiarities of chronic placental insufficiency formation caused by different types of diabetes mellitus. Diabetes mellitus. 2020;23(2):185–191. EDN: WMVKAO doi: 10.14341/DM10228

[20] Траль Т.Г., Толибова Г.Х., Мусина Е.В., и др. Молекулярно-морфологические особенности формирования хронической плацентарной недостаточности, обусловленной разными типами сахарного диабета // Сахарный диабет. 2020. Т. 23, № 2. С. 185–191. EDN: WMVKAO doi: 10.14341/DM10228

[21] 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

[22] Valencia-Ortega J., Saucedo R., Sánchez-Rodríguez M.A., et al. Epigenetic alterations related to gestational diabetes mellitus // Int J Mol Sci. 2021. Vol. 22, N. 17. P. 9462. doi: 10.3390/ijms22179462

[23] Horvatiček M, Perić M, Bečeheli I, et al. Maternal metabolic state and fetal sex and genotype modulate methylation of the serotonin receptor type 2A gene (HTR2A) in the human placenta. Biomedicines. 2022;10(2):467. doi: 10.3390/biomedicines10020467

[24] Horvatiček M., Perić M., Bečeheli I., et al. Maternal metabolic state and fetal sex and genotype modulate methylation of the serotonin receptor type 2A gene (HTR2A) in the human placenta // Biomedicines. 2022. Vol. 10, N. 2. P. 467. doi: 10.3390/biomedicines10020467

[25] Pavlova TV, Kaplin AN, Goncharov IYu, et al. Uteroplacental blood flow in maternal diabetes mellitus. Arkhiv Patologii. 2021;83(1):25–30. EDN: RTLQNV doi: 10.17116/patol20218301125

[26] Павлова Т.В., Каплин А.Н., Гончаров И.Ю, и др. Маточно-плацентарный кровоток при сахарном диабете у матери // Архив патологии. 2021. Т. 83, №. 1. С. 25–30. EDN: RTLQNV doi: 10.17116/patol20218301125

[27] Brodowski L, Rochow N, Yousuf EI, et al. The impact of parity and maternal obesity on the fetal outcomes of a non-selected Lower Saxony population. J Perinat Med. 2021;50(2):167–175. doi: 10.1515/jpm-2020-0614

[28] Brodowski L., Rochow N., Yousuf E.I., et al. The impact of parity and maternal obesity on the fetal outcomes of a non-selected Lower Saxony population // J Perinat Med. 2021. Vol. 50, N. 2. P. 167–175. doi: 10.1515/jpm-2020-0614

[29] Anderson MS, Flowers-Ziegler J, Das UG, et al. Glucose transporter protein responses to selective hyperglycemia or hyperinsulinemia in fetal sheep. Am J Physiol Regul Integr Comp Physiol. 2001;281(5):R1545–R1552. doi: 10.1152/ajpregu.2001.281.5.R1545

[30] Anderson M.S., Flowers-Ziegler J., Das U.G., et al. Glucose transporter protein responses to selective hyperglycemia or hyperinsulinemia in fetal sheep // Am J Physiol Regul Integr Comp Physiol. 2001. Vol. 281, N. 5. P. R1545–R1552. doi: 10.1152/ajpregu.2001.281.5.R1545

[31] Bönisch H, Fink KB, Malinowska B, et al. Serotonin and beyond — a tribute to Manfred Göthert (1939–2019). Naunyn Schmiedebergs Arch Pharmacol. 2021;394(9):1829–1867. doi: 10.1007/s00210-021-02083-5

[32] Bönisch H., Fink K.B., Malinowska B., et al. Serotonin and beyond — a tribute to Manfred Göthert (1939–2019) // Naunyn-Schmiedeberg’s Arch Pharmacol. 2021. Vol. 394, N. 9. P. 1829–1867. doi: 10.1007/s00210-021-02083-5

[33] Bettikher OA, Belyaeva OA, Dukovich AI, et al. Expression of the serotonergic system components in the placenta in various types of preeclampsia. Journal of Obstetrics and Women’s Diseases. 2023;72(1):5–16. EDN: BFRVOI doi: 10.17816/JOWD110890

[34] Беттихер О.А., Беляева О.А., Дукович А.И., и др. Экспрессия компонентов серотонинергической системы в плаценте при различных типах преэклампсии // Журнал акушерства и женских болезней. 2023. Т. 72, № 1. С. 5–16. EDN: BFRVOI doi: 10.17816/JOWD110890

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