Research Progress of Circular RNAs in Pregnancy and Pregnancy-Related Diseases

doi:10.12280/gjszjk.20260089

Abstract

Abstract:

Circular RNAs (circRNAs), as a group of crucial regulatory molecules, are capable of modulating gene expression and mediating signaling pathways, and exert vital functions in the sophisticated physiological process of pregnancy. Studies have demonstrated that circRNAs participate in the core physiological processes including embryonic development, placental formation and maternal-fetal interface signal transduction via multiple mechanisms such as competing endogenous RNA network, epigenetic regulation and protein-protein interaction. Specifically, circRNAs are involved in regulating trophoblast function, angiogenesis, glycolipid metabolism, immune homeostasis and decidualization. Dysregulated expressions of circRNAs are closely associated with the pathogenesis of multiple pregnancy-related diseases, including preeclampsia, gestational diabetes mellitus, recurrent spontaneous abortion, fetal growth restriction and intrahepatic cholestasis of pregnancy. It is necessary to explore the intervention strategies of circRNAs and identify specific circRNAs as early screening biomarkers for pregnancy-related diseases, which is helpful to facilitate the auxiliary diagnosis and treatment of pregnancy-related diseases.

Key words: RNA, Circular, Pregnancy, Pregnancy complications, Signal transduction, Biomarkers

PAN Peng, ZHANG Yu, YANG Xiao-qing. Research Progress of Circular RNAs in Pregnancy and Pregnancy-Related Diseases[J]. Journal of International Reproductive Health/Family Planning, 2026, 45(4): 342-346.

References 40

[1]	Zhou C, Qi M, Xu Z, et al. Regulatory role of circRNAs in mammalian pregnancy[J]. Reprod Biol, 2025, 25(3):101042. doi: 10.1016/j.repbio.2025.101042.
[2]	Fu X, Li Y, Zhang Z, et al. Emerging role of miRNAs, lncRNAs, and circRNAs in pregnancy-associated diseases[J]. Chin Med J(Engl), 2023, 136(11):1300-1310. doi: 10.1097/CM9.0000000000002595.
[3]	He L, Zheng S, Zhan F, et al. The role of necroptosis in pathological pregnancies: mechanisms and therapeutic opportunities[J]. J Reprod Immunol, 2025, 169:104460. doi: 10.1016/j.jri.2025. 104460.
[4]	Ma S, Chen Y, Gu Z, et al. Validating multicenter cohort circular RNA model for early screening and diagnosis of gestational diabetes mellitus[J]. Diabetes Metab J, 2025, 49(3):462-474. doi: 10.4093/dmj.2024.0205. pmid: 39978792
[5]	Parsanathan R, Sunil S, Byju R. Circular RNAs in cardiovascular disease: A paradigm shift in diagnosis and therapeutics[J]. Life Sci, 2025, 379:123877. doi: 10.1016/j.lfs.2025.123877.
[6]	Ghods FJ. Circular RNAs in Blood and Its Clinical Relevance[J]. Adv Exp Med Biol, 2025, 1485:197-210. doi: 10.1007/978-981-96-9428-0_13.
[7]	Srinivasan A, Mroczko-Młotek E, Wojciechowska M. Circular RNA Formation and Degradation Are Not Directed by Universal Pathways[J]. Int J Mol Sci, 2025, 26(2):726. doi: 10.3390/ijms26020726.
[8]	Wang X, Shan G. Features and biomedical relevance of circular RNA biogenesis[J]. Trends Genet, 2026, 42(3):282-294. doi: 10.1016/j.tig.2025.11.001.
[9]	Wang M, Zheng S, Zhang Y, et al. Transcriptome analysis reveals PTBP1 as a key regulator of circRNA biogenesis[J]. BMC Biol, 2025, 23(1):127. doi: 10.1186/s12915-025-02233-8. pmid: 40350413
[10]	Eleazer R, De Silva K, Andreeva K, et al. PARP1 Regulates Circular RNA Biogenesis though Control of Transcriptional Dynamics[J]. Cells, 2023, 12(8):1160. doi: 10.3390/cells12081160.
[11]	Joaquim V, Pereira NP, Fernandes T, et al. Circular RNAs as a Diagnostic and Therapeutic Target in Cardiovascular Diseases[J]. Int J Mol Sci, 2023, 24(3):2125. doi: 10.3390/ijms24032125.
[12]	Kuang L, Lei M, Li C, et al. Whole transcriptome sequencing reveals that non-coding RNAs are related to embryo morphogenesis and development in rabbits[J]. Genomics, 2020, 112(3):2203-2212. doi: 10.1016/j.ygeno.2019.12.016. pmid: 31881265
[13]	Fan Y, Pavani KC, Broeckx B, et al. Circular RNAs from bovine blastocysts can interact with miRNAs/tsRNAs from embryonic extracellular vesicles and regulate hatching[J]. Int J Biol Macromol, 2024, 277(Pt 4):134018. doi: 10.1016/j.ijbiomac. 2024.134018.
[14]	Lv C, Guo L, Wang Y, et al. circAMN1-Mediated Ferroptosis Regulates the Expulsion of Placenta in Trophoblast Cells[J]. Antioxidants(Basel), 2024, 13(4):451. doi: 10.3390/antiox 13040451.
[15]	廖灵蕴, 刘敏, 张燕萍, 等. 子痫前期孕妇胎盘组织中circRNA表达谱及circRNA-miRNA-mRNA相互作用网络分析[J]. 中华妇产科杂志, 2023, 58(6):430-441. doi: 10.3760/cma.j.cn112141- 20230206-00044.
[16]	Hu X, Xia W. Circ_0005714/miR-223-3p/ADAM9 regulatory axis affects proliferation, migration, invasion, and angiopoiesis in trophoblast cells[J]. Autoimmunity, 2022, 55(8):640-649. doi: 10.1080/08916934.2022.2101642.
[17]	Huang D, Ran Y, Chen R, et al. Identification of circRNA Expression Profile and Potential Systemic Immune Imbalance Modulation in Premature Rupture of Membranes[J]. Anal Cell Pathol(Amst), 2024, 2024:6724914. doi: 10.1155/2024/6724914.
[18]	Zou H, Mao Q. Circ_0037078 promotes trophoblast cell proliferation, migration, invasion and angiogenesis by miR-576-5p/IL1RAP axis[J]. Am J Reprod Immunol, 2022, 87(1):e13507. doi: 10.1111/aji.13507.
[19]	Wang Y, Liu L, Wang J, et al. Hsa_circ_0015382 is involved in the pathogenesis of preeclampsia by mediating THBS2 expression[J]. Am J Reprod Immunol, 2023, 90(3):e13760. doi: 10.1111/aji.13760.
[20]	Li Y, Chen J, Song S. Circ-OPHN1 suppresses the proliferation, migration, and invasion of trophoblast cells through mediating miR-558/THBS2 axis[J]. Drug Dev Res, 2022, 83(4):1034-1046. doi: 10.1002/ddr.21931.
[21]	Li K, Lv C, Zhang W, et al. CircFN1 upregulation initiated oxidative stress-induced apoptosis and inhibition of proliferation and migration in trophoblasts via circFN1-miR-19a/b-3p-ATF2 ceRNA network[J]. Reprod Biol, 2022, 22(2):100631. doi: 10.1016/j.repbio.2022.100631.
[22]	Shang J, Lin L, Huang X, et al. Re-expression of circ_0043610 contributes to trophoblast dysfunction through the miR-558/RYBP pathway in preeclampsia[J]. Endocr J, 2022, 69(12):1373-1385. doi: 10.1507/endocrj.EJ22-0153. pmid: 35908953
[23]	Xing H, Ding Q, Lu H, et al. Circ_0007611 stimulates IL-1 receptor accessory protein to inhibit trophoblast cell proliferation and induce cell apoptosis[J]. Biol Reprod, 2022, 106(5):1011-1021. doi: 10.1093/biolre/ioac028. pmid: 35238896
[24]	Li Z, Zhou X, Gao W, et al. Circular RNA VRK1 facilitates pre-eclampsia progression via sponging miR-221-3P to regulate PTEN/Akt[J]. J Cell Mol Med, 2022, 26(6):1826-1841. doi: 10.1111/jcmm.16454.
[25]	Wang X, Bian W, Huang M, et al. Extrachromosomal circular DNA drives ferroptosis and immunity in trophoblasts via the STING pathway in preeclampsia[J]. Biochem Biophys Res Commun, 2025, 781:152522. doi: 10.1016/j.bbrc.2025.152522.
[26]	Chen H, Zhang S, Wu Y, et al. The role of circular RNA circ_0008285 in gestational diabetes mellitus by regulating the biological functions of trophoblasts[J]. Biol Res, 2021, 54(1):14. doi: 10.1186/s40659-021-00337-3. pmid: 33879262
[27]	Wang J, Tuluhong M, Zhu Q. A Preliminary Study of circ-PNPT1/miR-144-3p/UBE2G1 Expression in Placental Tissues and Serum and Its Mechanism in Patients With Gestational Diabetes Mellitus[J]. Mol Reprod Dev, 2025, 92(9):e70057. doi: 10.1002/mrd. 70057.
[28]	Zhu C, Liu Y, Wu H. Overexpression of circACTR2 in Gestational Diabetes Mellitus Predicts Intrauterine Death, Fetal Malformation, and Intrauterine Infection[J]. Diabetes Metab Syndr Obes, 2021, 14:4655-4660. doi: 10.2147/DMSO.S316043.
[29]	Cao M, Bu C, Zhang J, et al. Exosomal Circular RNA hsa_circ_0046060 of Umbilical Cord Mesenchymal Stromal Cell Ameliorates Glucose Metabolism and Insulin Resistance in Gestational Diabetes Mellitus via the miR-338-3p/G6PC2 Axis[J]. Int J Endocrinol, 2022, 2022:9218113. doi: 10.1155/2022/9218113.
[30]	Chen X, Huang J, Peng Y, et al. The role of circRNA polyribonucleotide nucleoside transferase 1 on Gestational Diabetes Mellitus[J]. Cell Mol Biol(Noisy-le-grand), 2022, 68(6):148-154. doi: 10.14715/cmb/2022.68.6.24.
[31]	Liu B, Liu J, Qiu Y, et al. MITA Promotes Macrophage Proinflammatory Polarization and Its circRNA-Related Regulatory Mechanism in Recurrent Miscarriage[J]. Int J Mol Sci, 2023, 24(11):9545. doi: 10.3390/ijms24119545.
[32]	Su Y, Xu J, Gao R, et al. The Circ-CYP24A1-miR-224-PRLR Axis Impairs Cell Proliferation and Apoptosis in Recurrent Miscarriage[J]. Front Physiol, 2022, 13:778116. doi: 10.3389/fphys.2022.778116.
[33]	Wang W, Huang L, Lv J, et al. Silencing circRNA-ZFAND6 induces trophoblast apoptosis by activating the mitochondrial pathway through the miR-575/SOD2 axis in unexplained recurrent spontaneous abortion[J]. BMC Womens Health, 2025, 25(1):164. doi: 10.1186/s12905-025-03682-7. pmid: 40200350
[34]	Huang Z, Zhu L, Zhang Q, et al. Circular RNA hsa-circ-0005238 enhances trophoblast migration, invasion and suppresses apoptosis via the miR-370-3p/CDC25B axis[J]. Front Med(Lausanne), 2022, 9:943885. doi: 10.3389/fmed.2022.943885.
[35]	Yang T, Hu J, Zhang L, et al. CircCUL1 inhibits trophoblast cell migration and invasion and promotes cell autophagy by sponging hsa-miR-30e-3p in fetal growth restriction via the ANXA1/PI3K/AKT axis[J]. J Biochem Mol Toxicol, 2024, 38(7):e23759. doi: 10.1002/jbt.23759.
[36]	Zheng L, Tang R, Fang J, et al. Circular RNA hsa_circ_0081343 modulates trophoblast autophagy through Rbm8a nuclear translocation[J]. Placenta, 2024, 158:89-101. doi: 10.1016/j.placenta.2024.09.019. pmid: 39413593
[37]	Zheng L, Tang R, Ahmad F, et al. Circ_0081343 promotes autophagy and alleviates pyroptosis via PI3 K/AKT/HIF-1α axis in hypoxia-induced fetal growth restriction of mice[J]. Anim Cells Syst(Seoul), 2025, 29(1):312-324. doi: 10.1080/19768354. 2025.2498932.
[38]	Xiong L, Tang M, Xing S, et al. The role of noncoding RNA and its diagnostic potential in intrahepatic cholestasis of pregnancy: a research update[J]. Front Genet, 2023, 14:1239693. doi: 10.3389/fgene.2023.1239693.
[39]	Feng F, Lei L, Liao J, et al. Circ_0060731 mediated miR-21-5p-PDCD4/ESR1 pathway to induce apoptosis of placental trophoblasts in intrahepatic cholestasis of pregnancy[J]. Tissue Cell, 2022, 76:101771. doi: 10.1016/j.tice.2022.101771.
[40]	Ren J, Jin H, Zhu Y. The Role of Placental Non-Coding RNAs in Adverse Pregnancy Outcomes[J]. Int J Mol Sci, 2023, 24(5):5030. doi: 10.3390/ijms24055030.