Submissions are open for the upcoming issue.

Molecular Medicine Peer-reviewed scientific journal

Molecular Medicine

ОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕ2025, No. 1

Significance of altered neutrophil extracellular traps formation during the development of pregnancy complications among patients with gestational diabetes mellitus

Shamarakova M.V., Artem’eva K.A., Nizyaeva N.V., Zayratyants G.O., Stepanova I.I., Stepanov A.A., Achmetshina A.A., Dobrochotova Y.E., Mikhaleva L.M.

Authors and affiliations

M.V. Shamarakova(1), K.A. Artem’eva(2), N.V. Nizyaeva(2), G.O. Zayratyants(1), I.I. Stepanova(2),
A.A. Stepanov(2), A.A. Achmetshina(2), Y.E. Dobrochotova(3), L.M. Mikhaleva(2)
1-S.S. Yudin City Clinical Hospital, Kolomenskiy passage, 4, Moscow, 115446, Russian Federation;
2-Avtsyn Research Institute of Human Morphology of FSBSI “Petrovsky National Research Center of Surgery”,
Abrikosovsky lane, 2, Moscow, 119991, Russian Federation;
3-FSAEI HE “N.I.Pirogov Russian National Research Medical University” of the Ministry of Health
of the Russian Federation, Ostrovityanova str., 1, Moscow, 117513, Russian Federation

Pages
49–55
Published
2025
Section
ОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕ
Молекулярная медицина, 2025, № 1Issue2025, No. 1Go to the issue →
How to cite

Abstract

Introduction. The interest in neutrophil extracellular traps (NETs) in various conditions, including pregnancy complications was increased over the last decade. Accompanied by gestational diabetes mellitus (GDM) hyperglycemia contributes to neutrophil’s activation and the formation of NETs.
The aim of study. In this study, we assess NETosis and placental function parameters of women who received diet only or insulin for treatment of gestational diabetes (GDMD/GDMI).
Methods. PR3 circulating levels, associated with NETs formation and placental expression were analyzed by ELISA and immunohistochemistry respectively in GDMD (n=35), GDMI (n=30) and healthy pregnant women (n=30). Clinical data, placental alpha microglobulin-1 (PAMG), placental lactogen and trophoblast glycoprotein (TGB) immunohistochemistry expression were characterized in 30 placentas of GDMD, 20 – GDMI and 25 uncomplicated pregnancies.
Results. PR3 placental expression was increased in complicated pregnancies (GDMD – 60,94 vs 31,88, p<0,001, GDMI – 64,42 vs 31,88, р=0,009) with no statistical differences between GDMD and GDMI. Though placental protein expression indicated potential ischemia among GDMI patients, newborn’s condition was the same like healthy mother’s group. Placental protein expression and clinical data between GDMD and uncomplicated pregnancy women were similar.
Conclusion. The study proposes that NETosis in GDM patients in adequate therapy condition, perhaps don’t stimulate pregnancy complications, in contrast – presents consequences of preexisting placental damage.

Keywords

Authors and affiliations

M.V. Shamarakova(1), K.A. Artem’eva(2), N.V. Nizyaeva(2), G.O. Zayratyants(1), I.I. Stepanova(2),
A.A. Stepanov(2), A.A. Achmetshina(2), Y.E. Dobrochotova(3), L.M. Mikhaleva(2)
1-S.S. Yudin City Clinical Hospital, Kolomenskiy passage, 4, Moscow, 115446, Russian Federation;
2-Avtsyn Research Institute of Human Morphology of FSBSI “Petrovsky National Research Center of Surgery”,
Abrikosovsky lane, 2, Moscow, 119991, Russian Federation;
3-FSAEI HE “N.I.Pirogov Russian National Research Medical University” of the Ministry of Health
of the Russian Federation, Ostrovityanova str., 1, Moscow, 117513, Russian Federation

References

Herre M., Cedervall J., Mackman N., Olsson A.K. Neutrophil extracellular traps in the pathology of cancer and other inflammatory diseases. Physiol Rev. 2023; 103 (1): 277–312. https://doi.org 10.1152/physrev.00062.2021.

Morales-Primo A.U., Becker I., Zamora-Chimal J. Neutrophil extracellular trap-associated molecules: a review on their immunophysiological and inflammatory roles. Int Rev Immunol. 2022; 41 (2): 253–74. https://doi.org 10.1080/08830185.2021.1921174.

Islam M.M., Takeyama N. Role of Neutrophil Extracellular Traps in Health and Disease Pathophysiology: Recent Insights and Advances. Int. J. Mol. Sci. 2023; 24 (21): 15805. https://doi.org 10.3390/ijms242115805.

Zhang H., Wang Y., Qu M., Li W., Wu D., Cata J.P., Miao C. Neutrophil, neutrophil extracellular traps and endothelial cell dysfunction in sepsis. Clin Transl Med. 2023; 13 (1): e1170. https://doi.org 10.1002/ctm2.1170.

Воронова О.В., Милованов А.П., Михалева Л.М. Интеграционный подход в исследовании сосудов плаценты при преэклампсии. Клиническая и экспериментальная морфология. 2022; 11 (3): 30–44. DOI: 10.31088/CEM2022.11.3.30-44. [Voronova OV, Milovanov AP, Mikhaleva LM. Integration approach to study placental vessels in preeclampsia. Clinical and experimental morphology. 2022; 11 (3): 30–44. DOI: 10.31088/CEM2022.11.3.30-44 (in Russian)]

Tarry-Adkins J.L., Aiken C.E., Ozanne S.E. Neonatal, infant, and childhood growth following metformin versus insulin treatment for gestational diabetes: A systematic review and meta-analysis. PLoS Med. 2019; 16 (8): e1002848. https://doi.org 10.1371/journal.pmed.1002848.

Njeim R., Azar W.S., Fares A.H., Azar S.T., Kfoury Kassouf H., Eid A.A. NETosis contributes to the pathogenesis of diabetes and its complications. J. Mol. Endocrinol. 2020; 65 (4): 65–76. https://doi.org 10.1530/JME-20-0128.

Богданова И.М., Артемьева К.А., Болтовская М.Н., Низяева Н.В. Потенциальная роль нейтрофильных внеклеточных ловушек в патогенезе преэклампсии. Проблемы репродукции. 2023; 29 (1): 63–72. [Bogdanova IM, Artem’eva KA, Boltovskaya MN, Nizyaeva NV. The potential role of neutrophil extracellular traps in the pathogenesis of preeclampsia. Russian J. Of Human Reproduction. 2023; 29 (1): 63 72. https://doi.org/10.17116/repro20232901163 (in Russian)]

Nizyaeva N.V., Kulikova G.V., Nagovitsyna M.N., Kan N.E., Prozorovskaya K.N., Shchegolev A.I., Sukhikh G.T. Expression of MicroRNA-146a and MicroRNA-155 in Placental Villi in Early- and Late-Onset Preeclampsia. Bull Exp. Biol. Med. 2017; 163 (3): 394–9. https://doi.org 10.1007/s10517-017-3812-0.

Wang Y., Xiao Y., Zhong L., Ye D., Zhang J., Tu Y., Bornstein S.R., Zhou Z., Lam K.S., Xu A. Increased neutrophil elastase and proteinase 3 and augmented NETosis are closely associated with β-cell autoimmunity in patients with type 1 diabetes. Diabetes. 2014; 63 (12): 4239–48. https://doi.org 10.2337/db14-0480.

Старосветская Н.А., Назимова С.В., Степанова И.И. и др. Получение комплекса моноклональных антител для иммуногистохимических исследований в области физиологии и патологии репродукции. Клиническая и экспериментальная морфология. 2012; 2: 22–7. [Starosvetskaya N.A., Nazimova S.V., Stepanova I.I. et al. Production of monoclonal antibodies set for immunohistochemical studies in the field of physiology and pathology of human reproduction. Clinical and experimental morphology. 2012; 2: 22–7 (in Russian)]

Artemieva K.A., Stepanova Y.V., Stepanova I.I., Shamarakova M.V., Tikhonova N.B., Nizyaeva N.V., Tsakhilova S.G., Mikhaleva L.M. Morfofunctional and Molecular Changes in Placenta and Peripheral Blood in Preeclampsia and Gestational Diabetes Mellitus. Dokl Biol Sci. 2023; 513 (1): 387–94. DOI: 10.1134/S0012496623700722.

Aslanian-Kalkhoran L., Mehdizadeh A., Aghebati-Maleki L., Danaii S., Shahmohammadi-Farid S., Yousefi M. The role of neutrophils and neutrophil extracellular traps (NETs) in stages, outcomes and pregnancy complications. J. Reprod Immunol. 2024; 163: 104237. https://doi.org 10.1016/j.jri.2024.104237.

Vokalova L., van Breda S.V., Ye X.L., Huhn E.A., Than N.G., Hasler P., Lapaire O., Hoesli I., Rossi S.W., Hahn S. Excessive Neutrophil Activity in Gestational Diabetes Mellitus: Could It Contribute to the Development of Preeclampsia? Front Endocrinol (Lausanne). 2018; 9: 542. https://doi.org 10.3389/fendo.2018.00542.

Guillotin F., Fortier M., Portes M., Demattei C., Mousty E., Nouvellon E., Mercier E., Chea M., Letouzey V., Gris J.C., Bouvier S. Vital NETosis vs. suicidal NETosis during normal pregnancy and preeclampsia. Front Cell Dev Biol. 2023; 10: 1099038. https://doi.org 10.3389/fcell.2022.1099038.

Kärkkäinen H., Laitinen T., Heiskanen N., Saarelainen H., Valtonen P., Lyyra-Laitinen T., Vanninen E., Heinonen S. Need for insulin to control gestational diabetes is reflected in the ambulatory arterial stiffness index. BMC Pregnancy Childbirth. 2013; 13: 9. https://doi.org 10.1186/1471–2393-13-9.

Bergwik J., Kristiansson A., Allhorn M., Gram M., Åkerström B. Structure, Functions, and Physiological Roles of the Lipocalin α1-Microglobulin (A1M). Front Physiol. 2021; 12: 645650. https://doi.org 10.3389/fphys.2021.645650.

Sibiak R., Jankowski M., Gutaj P., Mozdziak P., Kempisty B., Wender-Ożegowska E. Placental Lactogen as a Marker of Maternal Obesity, Diabetes, and Fetal Growth Abnormalities: Current Knowledge and Clinical Perspectives. J. Clin. Med. 2020; 9 (4): 1142. https://doi.org 10.3390/jcm9041142.

Davenport B.N., Wilson R.L., Jones H.N. Interventions for placental insufficiency and fetal growth restriction. Placenta. 2022; 125: 4–9. https://doi.org 10.1016/j.placenta.2022.03.127.

Martin-Estal I., Castorena-Torres F. Gestational Diabetes Mellitus and Energy-Dense Diet: What Is the Role of the Insulin/IGF Axis? Front Endocrinol (Lausanne). 2022; 13: 916042. https://doi.org 10.3389/fendo.2022.916042.

Ruiz-Palacios M., Ruiz-Alcaraz A.J., Sanchez-Campillo M., Larqué E. Role of Insulin in Placental Transport of Nutrients in Gestational Diabetes Mellitus. Ann Nutr Metab. 2017; 70 (1): 16–25. https://doi.org 10.1159/000455904.

Muralimanoharan S., Maloyan A., Myatt L. Mitochondrial function and glucose metabolism in the placenta with gestational diabetes mellitus: role of miR-143. Clin Sci (Lond). 2016; 130 (11): 931–41. https://doi.org 10.1042/CS20160076. Alam S.M.K., Jasti S., Kshirsagar S.K., Tannetta D.S., Dragovic R.A., Redman C.W., Sargent I.L., Hodes H.C., Nauser T.L., Fortes T., Filler A.M., Behan K., Martin D.R., Fields T.A., Petroff B.K., Petroff M.G. Trophoblast Glycoprotein (TPGB/5T4) in Human Placenta: Expression, Regulation, and Presence in Extracellular Microvesicles and Exosomes. Reprod Sci. 2018; 25 (2): 185–97. https://doi.org 10.1177/1933719117707053.

How to cite

Shamarakova M.V., Artem’eva K.A., Nizyaeva N.V., Zayratyants G.O., Stepanova I.I., Stepanov A.A., Achmetshina A.A., Dobrochotova Y.E., Mikhaleva L.M. (2025). Significance of altered neutrophil extracellular traps formation during the development of pregnancy complications among patients with gestational diabetes mellitus. Molecular Medicine, 23(1), 49–55. https://doi.org/10.29296/24999490-2025-01-06

Article search and quick navigation

Navigation