Pathophysiological features of free radical oxidation in pregnant women of indigenous and non-indigenous populations of the Amur region with tissue iron deficiency during the first and second trimesters

Introduction. Oxidative stress during gestation is a physiological adaptive process: in early pregnancy, it regulates trophoblast invasion, spiral artery remodeling, and organogenesis. Iron deficiency (ID), as a multifunctional trace element, is associated not only with the risk of hemogenic and tissue hypoxia but also with an imbalance between free radical oxidation (FRO) and antioxidant defense (AOD) systems.

Aim. To identify the characteristics of FRO and AOD processes in iron-deficient states among pregnant women of indigenous and non-indigenous populations of the Amur region at initial antenatal visits corresponding to the conditional waves of cytotrophoblast invasion (first and second trimesters).

 Materials and methods. The study included 177 pregnant women newly registered in the first or second trimester, residing in urban (Khabarovsk city) and rural areas (Nanai District) of the Amur region. Three groups were formed based on residence and ethnicity: Group 1 – urban non-indigenous women of European descent (n = 59); Group 2 – rural non-indigenous women of European descent (n = 60); Group 3 – rural indigenous women (Nanai, small-numbered ethnic groups of the Amur region, Mongoloid race) (n = 58). Serum ferritin was measured by enzyme-linked immunosorbent assay. FRO parameters–total intensity of reactive oxygen species generation (S_sp), rate of peroxyl radical formation (S_ind1), and lipid hydroperoxide content (h₁) and AOD parameters–antiradical defense activity (S_ind2) and substrate peroxide resistance (h₂) were assessed using chemiluminescence analysis.

Results. Iron deficiency was significantly more prevalent in the second trimester across all groups, particularly among rural non-indigenous and indigenous women. An environmentally favorable FRO–AOD profile was observed in rural non-indigenous pregnant women: in the first trimester, they exhibited significantly lower FRO values (S_sp, S_ind1, especially h₁) alongside high antiradical defense activity and peroxide resistance. This pattern was less pronounced in the second trimester. Ethnic-specific features were noted in indigenous women, characterized by higher FRO (S_sp, S_ind1) and lower AOD (S_ind2, h₂) in the first trimester compared to the second.

Conclusion. The identified eco-ethnic characteristics of the FRO–AOD system under iron deficiency highlight the need to consider these findings when designing preventive and therapeutic strategies for pregnant women in the Russian Far East. 

1. Chiarello D.I., Abad C., Rojas D., Toledo F., Vázquez C.M., Mate A., Sobrevia L., Marín R. Oxidative stress: Normal pregnancy versus preeclampsia. Biochim. Biophys. Acta Mol. Basis Dis 2020; 1866(2):165354. https://doi.org/10.1016/j.bbadis.2018.12.005

2. Sultana Z., Qiao Y., Maiti K., Smith R. Involvement of oxidative stress in placental dysfunction, the pathophysiology of fetal death and pregnancy disorders. Reproduction 2023; 166(2): 25–38. https://doi.org/10.1530/REP-22-0278

3. WHO Global nutrition targets 2030: anaemia brief. Geneva: World Health Organization and the United Nations Children’s Fund (UNICEF). https://doi.org/10.2471/B09484. Available at: https://iris.who.int/handle/10665/383189

4. Vavina O.V., Puchko T.K., Umralieva M.A. [Iron deficiency anaemia in pregnancy and its correction]. Meditsinskiy sovet = Medical Council 2018; 13:73–76 (in Russian). https://doi.org/:10.21518/2079-701X-2018-13-73-76

5. Okladnikov S.M., editor. [Women and Men of Russia. Statistical compilation]. Moscow: Rosstat, 2024 (in Russian).

6. Lukina E.A., Dezhenkova A.V. [Iron metabolism in normal and pathological conditions]. Klinicheskaya onkogematologiya = Clinical oncohematology 2015; 8(4):355–361 (in Russian). https://doi.org/10.21320/2500-2139-2015-8-4-355-361

7. Solovyova A.V., Stuklov N.I., Apresyan S.V., Ivanov A.V. [Anemias and Reproductive Health. Radzinsky V.E., editor]. Moscow: Status Praesens; 2024 (in Russian). ISBN: 978-5-907814-06-6.

8. Roemhild K., Maltzahn F., Weiskirchen R., Knüchel R., Stillfried S., Lammers T. Iron metabolism: pathophysiology and pharmacology. Trends Pharmacol. Sci. 2021; 42(8):640–656. https://doi.org/10.1016/j.tips.2021.05.001

9. Atajanyan A.S. [Anaemia in pregnancy: cliniсо-pathogenetic approaches to the management of pregnancy]. Zhurnal akusherstva i zhenskikh bolesney = Journal of Obstetrics and Women’s Diseases 2017; 66(5):56–63. https://doi.org/10.17816/JOWD66556-63

10. Shestopalov A.V., Arutyunyan A.V., Akuyeva M.M., Shestopalova M.A., Bushtyreva I.O. [Oxidative stress in pathogenesis of placentation]. Zhurnal akusherstva i zhenskikh bolesney = Journal of Obstetrics and Women’s Diseases 2009; 58(1):193–100.

11. Zhao H., Wong R.J., Stevenson D.K. The impact of hypoxia in early pregnancy on placental cells. Int. J. Mol. Sci. 2021; 22(18):9675. https://doi.org/10.3390/ijms22189675

12. Colson A., Sonveaux P., Debie`ve F., Sferruzzi-Perri A.N. Adaptations of the human placenta to hypoxia: opportunities for interventions in fetal growth restriction. Hum. Reprod. Update 2021; 27(3):531–569. https://doi.org/10.1093/humupd/dmaa053

13. Huang X., Lin Z., Zheng Z-M., Shi J.-L., Lu K.-Y., Wang J.-R., Li M.-Q., Shao J. A hypoxia – decidual macrophage regulatory axis in normal pregnancy and spontaneous miscarriage. Int. J. Mol. Sci. 2024; 25(17):9710. https://doi.org/10.3390/ijms25179710

14. Herrera E.A., Krause B., Ebensperger G., Reyes R.V., Casanello P., Parra-Cordero M., Llanos A.J. The placental pursuit for an adequate oxidant balance between the mother and the fetus. Fron. Pharmacol. 2014; 5:149. https://doi.org/10.3389/fphar.2014.00149

15. Burlev V.A. [The role of endometrial blood vessels in the formation of the trophoblast and placenta]. Problemy reproduktologii = Russian Journal of Human Reproduction 2016; 22(6):8–17. https://doi.org/10.17116/repro20162268-17

16. Wakeland A.K., Soncin F., Moretto-Zita M., Chang Ch.-W., Horii M., Pizzo D., Nelson K.K., Laurent L.C., Parast M.M. Hypoxia directs human extravillous trophoblast differentiation in a hypoxia-inducible factor-dependent manner. Am. J. Pathol. 2017; 187(4):767–780. http://dx.doi.org/10.1016/j.ajpath.2016.11.018

17. Radzinsky V.E. [Obstetric Aggression]. Moscow: Status Praesens; 2011 (in Russian).

18. Milovanov A.P. [Cytotrophoblastic invasion is the most important mechanism of placentation and pregnancy progression]. Arkhiv patologii = Archive of patology 2019; 81(4):5–10. https://doi.org/10.17116/patol2019810415

19. Valko M., Leibfritz D., Moncol J., Cronin M.T.D., Mazur M., Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol. 2007; 39(1): 44–84. https://doi.org/10.1016/j.biocel.2006.07.001

20. Knuppel R.A., Hassan M.I., McDermott J.J., Tucker J.M., Morrison J.C. Oxidative stress and antioxidants: preterm birth and preterm infants. In: Morrison J.C., editor. Preterm Birth - Mother and Child. Rijeka (Croatia): InTech; 2012: 125–150. https://doi.org/10.5772/38970

21. Juan-Reyes S.S., Gómez-Oliván L.M., Islas-Flores H., Dublán-García O. Oxidative stress in pregnancy complicated by preeclampsia. Arch. Biochem. Biophys. 2020; 681:108255. https://doi.org/10.1016/j.abb.2020.108255

22. Toboła-Wróbel K., Pietryga M., Dydowicz P., Napierała M., Brązert J., Florek E. Association of oxidative stress on pregnancy. Oxid. Med. Cell. Longev 2020; 2020:6398520. https://doi.org/10.1155/2020/6398520

23. Ibrahim A., Khoo M.I., Ismail E.H.E., Hussain N.H.N., Zin A.A.M., Noordin L., Abdullah S., Mahdy Z.A., Lah N.A.Z.N. Oxidative stress biomarkers in pregnancy: a systematic review. Reprod. Biol. Endocrinol. 2024; 22(1): 93. https://doi.org/10.1186/s12958-024-01259-x

24. Vladimirov Yu.A., Azizova O.A. [Free Radicals in Living Systems]. Moscow: VINITI; 1991 (in Russian).

25. Ajepe A.A., Okunade K.S., Sekumade A.I., Daramola E.S., Beke M.O., Ijasan O., Olowoselu O.F., Afolabi B.B. Prevalence and foetomaternal effects of iron deficiency anaemia among pregnant women in Lagos, Nigeria. PLoS One 2020; 15(1):e0227965. https://doi.org/10.1371/journal.pone.0227965