Placental expression of hypoxia-induced factors in acute hypoxia and fetal intrauterine growth restriction
Leonova M.D., Bezhenar V.F., Semenova N.Yu., Semenikhin D.V., Frederiks E.V.
Hypoxia-induced factors (HIF-1 and HIF-2) are expressed in the placenta during all trimesters of pregnancy under both normal and hypoxic conditions. However, hypoxia significantly increases placental expression of HIF-1 and HIF-2. The role of HIF-1 expression in chronic placental insufficiency, its significance in preterm birth and preeclampsia, and the relationship between inflammation and hypoxia has been established. Nevertheless, there is a lack of data regarding placental HIF expression at birth in children who experience acute hypoxia during labor.
Objective: To determine the levels of placental HIF-1 and HIF-2 expression in acute hypoxia during labor and fetal intrauterine growth restriction (IUGR).
Materials and methods: An immunohistochemical study was conducted on 44 placentas using primary rabbit antibodies for HIF1a and HIF2a, divided into three groups: group I (n=12), comprising placentas obtained during uncomplicated labor; group II (n=18), consisting of placentas from fetuses that experienced hypoxia during labor (umbilical artery blood pH <7.25); and group III (n=14), including placentas with fetal IUGR.
Results: A statistically significant difference in HIF-1 expression was observed between groups I and III. When assessing the intensity of HIF-1 and HIF-2 staining, significant differences were noted between groups I and II and between groups I and III, while expression in groups II and III did not differ. The highest placental HIF-2 expression was observed in newborn girls.
Conclusion: The results indicate that HIF-1 and HIF-2 expression changes depending on the duration of cell exposure to hypoxia. The maximum placental expression of hypoxia-induced factors is characteristic of fetal IUGR.
Authors' contributions: Bezhenar V.F., Frederiks E.V. – conception and design of the study; Leonova M.D. – collection and processing of material, statistical analysis, writing of the text; Semenikhin D.V., Semenova N.Yu. – pathomorphological and immunohistochemical studies; Bezhenar V.F. – editing of the manuscript. All authors made significant contributions to the study and drafting of the manuscript, and they read and approved the final version before submission.
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 Pavlov First St. Petersburg SMU, Ministry of Health of Russia.
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: Leonova M.D., Bezhenar V.F., Semenova N.Yu., Semenikhin D.V., Frederiks E.V.
Placental expression of hypoxia-induced factors in acute hypoxia and fetal intrauterine growth restriction.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (6): 106-113 (in Russian)
https://dx.doi.org/10.18565/aig.2025.55
Keywords
placental expression
hypoxia-induced factors
HIF-1
HIF-2
fetal hypoxia
fetal IUGR
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Received 28.02.2025
Accepted 21.05.2025
About the Authors
Margarita D. Leonova, Obstetrician-Gynecologist, Maternity Hospital No. 13, 191124, Russia, St. Petersburg, Kostromskaya str., 4, +7(812)275-68-70,_margarita_@bk.ru, https://orcid.org/0000-0002-3813-2995
Vitaly F. Bezhenar, Dr. Med. Sci., Professor, Head of the Departments of Obstetrics, Gynecology and Neonatology/Reproductology, Head of the Clinic of Obstetrics and Gynecology, Pavlov First State Medical University, Ministry of Health of Russia, 197022, Russia, St. Petersburg, Leo Tolstoy str., 6-8; Main Supernumerary Specialist Obstetrician-Gynecologist of the Health Committee of St. Petersburg, +7(812)338-78-66, bez-vitaly@yandex.ru, https://orcid.org/0000-0002-7807-4929
Natalia Yu. Semenova, PhD, Head of Scientific Department, Morfolab, St. Petersburg, Russia, https://orcid.org/0000-0003-4069-0678
Dmitry V. Semenikhin, Pathologist, Chief Physician, Morfolab, Russia, St. Petersburg, https://orcid.org/0000-0002-0636-5241
Elena V. Frederiks, PhD, Chief Physician, Maternity Hospital No. 13, 191124, Russia, St. Petersburg, Kostromskaya str. 4; Teaching Assistant at the Department of Obstetrics, Gynecology and Neonatology, Pavlov First State Medical University, Ministry of Health of Russia, 197022, Russia, St. Petersburg, Leo Tolstoy str., 6-8,
https://orcid.org/0000-0002-2513-6209
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