Criteria for assessing fetal neurogenesis dysfunction in early-onset growth restriction using extracellular vesicles
Kan N.E., Leonova A.A., Gusar V.A., Chagovets V.V., Tyutyunnik V.L., Volochaeva M.V., Soldatova E.E., Ryzhova K.O., Serebriakova A.P.
Objective: To evaluate neurogenesis dysfunction during early-onset fetal growth restriction by obtaining fetal neuronal exosomes (FNE) from maternal plasma, assessing the expression of neurotrophin proteins involved in neurogenesis and the regulation of fetal nervous system plasticity, and establishing relationships with clinical and functional data.
Materials and methods: This study included 45 pregnant women. The study group consisted of 20 women with early-onset fetal growth restriction, whereas the control group comprised 25 women with normal pregnancies. The gestational age of the newborns in both groups did not exceed 34 weeks. Extracellular vesicles were isolated from maternal plasma using a commercial kit, followed by immunoprecipitation to obtain FNE. The expression of neurotrophin proteins—nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)—was assessed using Western blotting.
Results: A decrease in the expression of BDNF (pro-BDNF) and NGF (pro-NGF) precursors was observed in the FNE of the study group. Mature forms of neurotrophin proteins were not detected in FNE. Changes in pro-BDNF levels were noted only in cases of intraventricular hemorrhage (IVH), while pro-NGF levels varied in IVH, cerebral ischemia, and asphyxia in newborns during the neonatal period.
Conclusion: The results demonstrate, for the first time, the potential to detect brain neurodysfunction in fetuses with growth restriction by assessing the expression of neuronal proteins in FNE isolated from maternal blood via immunoprecipitation. Changes in these protein levels may reflect the degree of brain dysfunction and serve as potential prognostic and diagnostic markers of pathological conditions.
Authors' contributions: Kan N.E., Leonova A.A., Gusar V.A., Chagovets V.V., Tyutyunnik V.L., Volochaeva M.V., Soldatova E.E., Ryzhova K.O., Serebriakova A.P. – conception and design of the study, acquisition of data for analysis, review of literature, preparation and analysis of material on the topic, statistical analysis, drafting of the manuscript, editing of the manuscript.
Conflicts of interest: The authors have no conflicts of interest to declare.
Funding: The study was conducted within the framework of the initiative project "Epigenetic criteria for diagnosis of fetal growth restriction from the perspective of neurogenesis dysfunction" (research project No. 19-И23 dated 8 December 2022) (registration number in the EGISU NIOKTR system (state accounting) – 123060500032-8).
Ethical Approval: The study was reviewed and approved by the Research Ethics Committee of the V.I. Kulakov NMRC for OG&P.
Patient Consent for Publication: All patients provided informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.
For citation: Kan N.E., Leonova A.A., Gusar V.A., Chagovets V.V., Tyutyunnik V.L., Volochaeva M.V., Soldatova E.E., Ryzhova K.O., Serebriakova A.P. Criteria for assessing fetal neurogenesis dysfunction
in early-onset growth restriction using extracellular vesicles.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (3): 56-64 (in Russian)
https://dx.doi.org/10.18565/aig.2025.30
Keywords
extracellular vesicles
fetal growth restriction
fetal neuronal exosomes
neurogenesis
placental dysfunction
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Received 11.02.2025.
Accepted 28.02.2025
About the Authors
Natalia E. Kan, Professor, Dr. Med. Sci., Merited Scholar of the Russian Federation, Deputy Director for Research – Director of the Institute of Obstetrics,Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow,
Ac. Oparin str., 4, kan-med@mail.ru, Researcher ID: B-2370-2015, SPIN: 5378-8437, Authors ID: 624900, Scopus Author ID: 57008835600,
https://orcid.org/0000-0001-5087-5946
Anastasia A. Leonova, PhD student, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, +7(937)453-54-27, nastena27-03@mail.ru, https://orcid.org/0000-0001-6707-3464
Vladislava E. Gusar, PhD, Senior Researcher at the Laboratory of Transcriptomic, Department of Systems Biology in Reproduction, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, v_gusar@oparina4.ru,
https://orcid.org/0000-0003-3990-6224
Vitaliy V. Chagovets, PhD, Senior Researcher at the Laboratory of Transcriptomic, Department of Systems Biology in Reproduction, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, vvchagovets@gmail.com,
https://orcid.org/0000-0002-5120-376X
Victor L. Tyutyunnik, Professor, Dr. Med. Sci., Leading Researcher at the Center for Scientific and Clinical Research, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, tioutiounnik@mail.ru,
Researcher ID: B-2364-2015, SPIN: 1963-1359, Authors ID: 213217, Scopus Author ID: 56190621500, https://orcid.org/0000-0002-5830-5099
Maria V. Volochaeva, PhD, Senior Researcher at the Department of Regional Cooperation and Integration, Physician at 1 Maternity Department, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4,
m_volochaeva@oparina4.ru, https://orcid.org/0000-0001-8953-7952
Ekaterina E. Soldatova, Researcher at the Obstetric Department of the Institute of Obstetrics, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, katerina.soldatova95@bk.ru, https://orcid.org/0000-0001-6463-3403
Kristina O. Ryzhova, Resident, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia,
117997, Russia, Moscow, Ac. Oparin str., 4, cr.yanina@gmail.com, https://orcid.org/0009-0007-8318-435X
Anna P. Serebriakova, obstetrician-gynecologist of the Day Hospital Department, Primorsky Regional Perinatal Center, 690042, Russia, Vladivostok, Mozhayskaya str., 1B, serebriakovanna@gmail.com, https://orcid.org/0000-0001-7014-2627
Corresponding author: Anastasia A. Leonova, nastena27-03@mail.ru
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