The role of mitochondrial dysfunction in the pathogenesis of preterm birth
Medzhidova M.K., Tyutyunnik V.L., Kan N.E., Manukhova L.A., Marey M.V., Ivanova V.A., Vysokikh M.Yu.
Objective. To evaluate the role of placental and fetal membrane mitochondrial dysfunction in the pathogenesis of preterm birth (PTB).
Materials and methods. This study included 228 women with spontaneous preterm birth at 22.0–37.0 weeks of gestation. The participants were divided into four groups: Group 1 comprised 52 women with extremely preterm birth (22.0–27.6 weeks); Group 2 included 56 women with early preterm birth (28.0–31.6 weeks); Group 3 consisted of 60 women with preterm birth (32.0–33.6 weeks); and Group 4 included 60 women with late preterm birth (34.0–36.6 weeks). Given the different etiological pathways of PTB, each group was further subdivided into two subgroups: women with preterm prelabor rupture of membranes (PPROM) followed by spontaneous onset of labor (n=125) and women with spontaneous preterm birth (SPB) without PPROM (n=103). The control group comprised 72 women with uncomplicated pregnancies who delivered at term (37.0–41.0 weeks).
Results. Statistically significant differences in placental OPA1 protein expression were identified between the spontaneous preterm birth and term birth groups, with significantly higher OPA1 levels in the spontaneous preterm birth group (p<0.01).
PINK1 expression was significantly decreased in the placenta of spontaneous preterm birth compared with term birth (p<0.01). Analysis of PARKIN protein expression, functionally associated with PINK1 activity, revealed statistically significant differences between all PTB groups and the term birth group (p<0.01).
Placental P62 protein levels showed statistically significant differences between extremely preterm and late preterm births (p<0.01) and between extremely preterm and term births (p<0.001). Elevated P62 levels in extremely preterm births indicate autophagy activation in the context of mitophagy imbalance, resulting in impaired clearance of damaged mitochondria.
Conclusion. Disruption of mitophagy and autophagy pathways (P62, PINK1, and PARKIN) in the placenta represents a common but differentially regulated mechanism underlying the pathogenesis of both spontaneous preterm birth and PPROM. These findings support the hypothesis that mitochondrial quality control plays a critical role in maintaining pregnancy. Altered expression of P62, PARKIN, and PINK1 in spontaneous preterm birth and PPROM suggests that defects in mitochondrial quality control are key components in the pathogenesis of preterm birth.
Authors' contributions. Medzhidova M.K., Tyutyunnik V.L., Kan N.E., Vysokikh M.Yu., Marey M.V. – conception and design of the study; Medzhidova M.K., Manukhova L.A., Marey M.V., Ivanova V.A. – data collection and analysis and review of the relevant literature; Medzhidova M.K. – drafting of the manuscript; Tyutyunnik V.L., Kan N.E., Vysokikh M.Yu. – editing of the manuscript.
Conflicts of interest. The authors have no conflicts of interest to declare.
Funding. There was no funding for this study.
Ethical Approval. The study was reviewed and approved by the Research Ethics Committee of the V.I. Kulakov NMRC for OG&P.
Generative Artificial Intelligence. No artificial intelligence tools were used in the preparation of this manuscript.
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: Medzhidova M.K., Tyutyunnik V.L., Kan N.E., Manukhova L.A., Marey M.V., Ivanova V.A.,
Vysokikh M.Yu. The role of mitochondrial dysfunction in the pathogenesis of preterm birth.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2026; (7): 86-93 (in Russian)
https://dx.doi.org/10.18565/aig.2026.82
Keywords
preterm birth
spontaneous preterm birth (SPB)
preterm premature rupture of membranes (PPROM)
mitochondrial dysfunction
mitochondrial biogenesis
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Received 05.03.2026
Accepted 15.06.2026
About the Authors
Marzhanat К. Medzhidova, PhD, Doctoral Student, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4, +7(926)381-17-10, marzhana-m@yandex.ru, Researcher ID: GRR-7195-2022, SPIN-code: 5942-2320,Authors ID: 116298611:49, Scopus Author ID: 57191960453, https://orcid.org/0000-0001-6938-4207
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. Oparina str., 4, +7(903)969-50-41, tioutiounnik@mail.ru, Researcher ID: B-2364-2015, SPIN-code: 1963-1359, Authors ID: 213217, Scopus Author ID: 56190621500, https://orcid.org/0000-0002-5830-5099
Natalia E. Kan, Professor, Dr. Med. Sci., Deputy Director of Science, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4, +7(926)220-86-55, kan-med@mail.ru, Researcher ID: B-2370-2015,
SPIN-code: 5378-8437, Authors ID: 624900, Scopus Author ID: 57008835600, https://orcid.org/0000-0001-5087-5946
Lyudmila A. Manukhova, Researcher at the Mitochondrial Medicine Research Group, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russia, 117997, Russia, Moscow, Ac. Oparina str., 4.
Maria V. Marey, PhD (Bio), Senior Researcher at the Mitochondrial Medicine Research Group, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russia, 117997, Russia, Moscow, Ac. Oparina str., 4, m_marey@oparina4.ru
Victorya A. Ivanova, Russian University of Medicine, Ministry of Health of the Russian Federation, 127006, Russia, Moscow, Dolgorukovskaya str., 4,
viktorya12311@gmail.com, https://orcid.org/0009-0008-4193-2548
Mikhail Yu. Vysokikh, PhD, Head of Mitochondrial Medicine Research Group, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russia, 117997, Russia, Moscow, Ac. Oparina str., 4, +7(495)438-76-33 (ex. 1472), m_vysokikh@oparina4.ru,
Researcher ID: H-4744-2014, SPIN-код: 2742-0833, Authors ID: 6602218584, Scopus Author ID: 57008835600, https://orcid.org/0000-0002-4047-6201
Corresponding author: Marzhanat К. Medzhidova, marzhana-m@yandex.ru
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