The Role of Oxidative Stress in Patients with Recurrent Pregnancy Loss: a Review

Overview

Journal Reprod Health

Publisher Biomed Central

Specialty Reproductive Medicine

Date 2021 Oct 17

PMID 34656123

Citations 18

Authors

Vjosa A Zejnullahu

Valon A Zejnullahu

Ernad Kosumi

Affiliations

Soon will be listed here.

Abstract

Background: Recurrent pregnancy loss (RPL) presents one of the main problems in the field of reproductive medicine, due to the unknown etiology in 50% of cases, as well as limited evidence-based diagnostic and therapeutic modalities. Recent studies indicate that systemic and placental oxidative stress (OS) represents an essential factor in the etiopathogenesis of RPL. This article is a comprehensive narrative synthesis of previously published studies concerning the role of oxidative stress in the etiology of recurrent pregnancy loss.

Methods: We conducted literature search of published studies in the English language focusing on oxidative stress and its association with recurrent pregnancy loss (RPL) utilizing the Medline and Cochrane databases from 2000 through January 2021. The keywords used were "recurrent pregnancy loss" "oxidative stress and recurrent pregnancy loss" and "oxidative stress biomarkers and recurrent pregnancy loss".

Results: The search yielded 1116 publications, of which 92 were included in the final analysis. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) at basal levels have various physiological functions whereas deviation from redox window is associated with different pathologies including early pregnancy loss. The currently available studies support the concept that increased oxidative stress (OS) and deficient antioxidant protection is implicated in the etiology of recurrent pregnancy loss (RPL) but underlying mechanisms through which OS affects pregnancy outcome remains largely indefinable.

Conclusions: Future research in this field can provide new insights regarding the OS-mediated damage in recurrent pregnancy loss as well as potential applications of antioxidant therapy in this group of patients.

Citing Articles

Hsa-miR-532-3p protects human decidual mesenchymal stem cells from oxidative stress in recurrent spontaneous abortion via targeting KEAP1.

Zhou H, Zhou J, Liu S, Niu J, Pan J, Li R Redox Biol. 2025; 80:103508.

PMID: 39908863 PMC: 11847473. DOI: 10.1016/j.redox.2025.103508.

Exploring the application of dietary antioxidant index for disease risk assessment: a comprehensive review.

Pourmontaseri H, Bazmi S, Sepehrinia M, Mostafavi A, Arefnezhad R, Homayounfar R Front Nutr. 2025; 11:1497364.

PMID: 39885868 PMC: 11781229. DOI: 10.3389/fnut.2024.1497364.

Micronutrient-Antioxidant Therapy and Male Fertility Improvement During ART Cycles.

Lahimer M, Capelle S, Lefranc E, Bosquet D, Kazdar N, Ledu A Nutrients. 2025; 17(2).

PMID: 39861453 PMC: 11768505. DOI: 10.3390/nu17020324.

Antioxidant therapy for infertile couples: a comprehensive review of the current status and consideration of future prospects.

Saleh R, Sallam H, Elsuity M, Dutta S, Sengupta P, Nasr A Front Endocrinol (Lausanne). 2025; 15():1503905.

PMID: 39850484 PMC: 11756326. DOI: 10.3389/fendo.2024.1503905.

Oxidative stress and its role in recurrent pregnancy loss: mechanisms and implications.

Zhang X, Gao J, Yang L, Feng X, Yuan X J Mol Histol. 2024; 56(1):55.

PMID: 39724438 DOI: 10.1007/s10735-024-10332-z.

References

Wruck C, Fragoulis A, Gurzynski A, Brandenburg L, Kan Y, Chan K . Role of oxidative stress in rheumatoid arthritis: insights from the Nrf2-knockout mice. Ann Rheum Dis. 2010; 70(5):844-50. DOI: 10.1136/ard.2010.132720. View

Kohchi C, Inagawa H, Nishizawa T, Soma G . ROS and innate immunity. Anticancer Res. 2009; 29(3):817-21. View

Zhang B, Dai B, Zhang X, Wang Z . Vascular endothelial growth factor and recurrent spontaneous abortion: a meta-analysis. Gene. 2012; 507(1):1-8. DOI: 10.1016/j.gene.2012.06.049. View

Zidi-Jrah I, Hajlaoui A, Mougou-Zerelli S, Kammoun M, Meniaoui I, Sallem A . Relationship between sperm aneuploidy, sperm DNA integrity, chromatin packaging, traditional semen parameters, and recurrent pregnancy loss. Fertil Steril. 2015; 105(1):58-64. DOI: 10.1016/j.fertnstert.2015.09.041. View

Liemburg-Apers D, Willems P, Koopman W, Grefte S . Interactions between mitochondrial reactive oxygen species and cellular glucose metabolism. Arch Toxicol. 2015; 89(8):1209-26. PMC: 4508370. DOI: 10.1007/s00204-015-1520-y. View

Webster R, Roberts V, Myatt L . Protein nitration in placenta - functional significance. Placenta. 2008; 29(12):985-94. PMC: 2630542. DOI: 10.1016/j.placenta.2008.09.003. View

Hernandez I, Fournier T, Chissey A, Therond P, Slama A, Beaudeux J . NADPH oxidase is the major source of placental superoxide in early pregnancy: association with MAPK pathway activation. Sci Rep. 2019; 9(1):13962. PMC: 6764989. DOI: 10.1038/s41598-019-50417-4. View

Amirchaghmaghi E, Rezaei A, Moini A, Roghaei M, Hafezi M, Aflatoonian R . Gene expression analysis of VEGF and its receptors and assessment of its serum level in unexplained recurrent spontaneous abortion. Cell J. 2015; 16(4):538-45. PMC: 4297492. DOI: 10.22074/cellj.2015.498. View

Thomas V, Knight R, Haswell S, Lindow S, van der Spuy Z . Maternal hair selenium levels as a possible long-term nutritional indicator of recurrent pregnancy loss. BMC Womens Health. 2013; 13:40. PMC: 4015529. DOI: 10.1186/1472-6874-13-40. View

10.

Schafer F, Buettner G . Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med. 2001; 30(11):1191-212. DOI: 10.1016/s0891-5849(01)00480-4. View

11.

Choi H, Choi B, Lee S, Kim J, Cha K, Baek K . Expression of angiogenesis- and apoptosis-related genes in chorionic villi derived from recurrent pregnancy loss patients. Mol Reprod Dev. 2003; 66(1):24-31. DOI: 10.1002/mrd.10331. View

12.

Drose S, Brandt U . Molecular mechanisms of superoxide production by the mitochondrial respiratory chain. Adv Exp Med Biol. 2012; 748:145-69. DOI: 10.1007/978-1-4614-3573-0_6. View

13.

Al-Sheikh Y, Ghneim H, Alharbi A, Alshebly M, Aljaser F, Aboul-Soud M . Molecular and biochemical investigations of key antioxidant/oxidant molecules in Saudi patients with recurrent miscarriage. Exp Ther Med. 2019; 18(6):4450-4460. PMC: 6861946. DOI: 10.3892/etm.2019.8082. View

14.

Glueck C, Wang P, Goldenberg N, Sieve-Smith L . Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin. Hum Reprod. 2002; 17(11):2858-64. DOI: 10.1093/humrep/17.11.2858. View

15.

Ray P, Huang B, Tsuji Y . Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 2012; 24(5):981-90. PMC: 3454471. DOI: 10.1016/j.cellsig.2012.01.008. View

16.

Starkov A . The role of mitochondria in reactive oxygen species metabolism and signaling. Ann N Y Acad Sci. 2008; 1147:37-52. PMC: 2869479. DOI: 10.1196/annals.1427.015. View

17.

Del Rio L, Sandalio L, Corpas F, Palma J, Barroso J . Reactive oxygen species and reactive nitrogen species in peroxisomes. Production, scavenging, and role in cell signaling. Plant Physiol. 2006; 141(2):330-5. PMC: 1475433. DOI: 10.1104/pp.106.078204. View

18.

Lucas E, Dyer N, Murakami K, Lee Y, Chan Y, Grimaldi G . Loss of Endometrial Plasticity in Recurrent Pregnancy Loss. Stem Cells. 2015; 34(2):346-56. DOI: 10.1002/stem.2222. View

19.

Su M, Lin S, Chen Y . Genetic association studies of angiogenesis- and vasoconstriction-related genes in women with recurrent pregnancy loss: a systematic review and meta-analysis. Hum Reprod Update. 2011; 17(6):803-12. DOI: 10.1093/humupd/dmr027. View

20.

El-Far M, El-Sayed I, El-Motwally A, Hashem I, Bakry N . Tumor necrosis factor-alpha and oxidant status are essential participating factors in unexplained recurrent spontaneous abortions. Clin Chem Lab Med. 2007; 45(7):879-83. DOI: 10.1515/CCLM.2007.138. View