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Licensed Unlicensed Requires Authentication Published online by De Gruyter May 23, 2022

Expression pattern and clinical significance of microRNA-let-7a and IFN-gamma in placental tissue of patients with preeclampsia with severe features

Liping Wang, Xiaojie Yuan and Xuewu Zhou

Abstract

Objectives

Preeclampsia with severe features (PECsf) is a common disease in pregnant women. let-7a and IFN-gamma (interferon-gamma) are involved in diagnosis and prognosis of preeclampsia. This study explored effects of let-7a and IFN-gamma on PECsf patients.

Methods

The placental tissue of 21 PECsf, 19 preeclampsia without severe features (PEC), and 20 normal pregnant women were collected, and clinical data were recorded. let-7a and IFN-gamma expressions in placental tissue were detected. The correlation between let-7a/IFN-gamma expression and clinical indexes was analyzed. According to let-7a and IFN-gamma expressions, PECsf patients were assigned into Hlet-7a group (let-7a high expression group), Llet-7a group (let-7a low expression group), HIFN-gamma group (IFN-gamma high expression group) and LIFN-gamma group (IFN-gamma low expression group). The incidence of adverse prognosis was compared.

Results

let-7a and IFN-gamma were highly expressed in placental tissue of preeclampsia patients, with significant differences between PEC and PECsf. The high expressions of let-7a and IFN-gamma were positively correlated with mean arterial pressure, lactate dehydrogenase, and 24 h urinary protein in placental tissues of PECsf patients. High let-7a and IFN-gamma expressions were correlated with adverse outcomes of PECsf.

Conclusions

High let-7a and IFN-gamma expressions were correlated with clinical features, and could be used as biomarkers for treatment and poor prognosis of PECsf.


Corresponding Authors: Liping Wang and Xiaojie Yuan, Department of Obstetrics and Gynecology, Daqing Longnan Hospital, Daqing, Heilongjiang, P. R. China, E-mail: (L. Wang), (X. Yuan), Phone: 19904860666
Liping Wang, Xiaojie Yuan and Xuewu Zhou contributed equally to this work.

  1. Research funding: Not applicable.

  2. Author contributions: LPW, XJY and XWZ contributed to the study concepts, study design, and definition of intellectual content; XJY contributed to the literature research; LPW contributed to the manuscript preparation; XJY and XWZ contributed to the manuscript editing and review; LPW, XJY and XWZ contributed to the experimental studies and data acquisition; LPW, XJY and XWZ contributed to the data analysis and statistical analysis. All authors read and approved the final manuscript.

  3. Competing interests: All authors declare that there is no conflict of interests in this study.

  4. Ethics approval: The experiments were authorized by the academic ethics committee of Daqing Longnan Hospital. All procedures were strictly implemented by the code of ethics. All the subjects involved were fully informed of the objective of the study and signed informed consent before sampling.

  5. Data availability: All the data generated or analyzed during this study are included in this published article.

References

1. Filipek, A, Jurewicz, E. [Preeclampsia - a disease of pregnant women]. Postepy Biochem 2018;64:232–29. https://doi.org/10.18388/pb.2018_146.Search in Google Scholar PubMed

2. Pinheiro, MB, Gomes, KB, Ronda, CR, Guimaraes, GG, Freitas, LG, Teixeira-Carvalho, A, et al.. Severe preeclampsia: association of genes polymorphisms and maternal cytokines production in Brazilian population. Cytokine 2015;71:232–7. https://doi.org/10.1016/j.cyto.2014.10.021.Search in Google Scholar PubMed

3. Rana, S, Lemoine, E, Granger, JP, Karumanchi, SA. Correction to: preeclampsia: pathophysiology, challenges, and perspectives. Circ Res 2020;126:e8. https://doi.org/10.1161/RES.0000000000000315.Search in Google Scholar PubMed

4. Bokslag, A, van Weissenbruch, M, Mol, BW, de Groot, CJ. Preeclampsia; short and long-term consequences for mother and neonate. Early Hum Dev 2016;102:47–50. https://doi.org/10.1016/j.earlhumdev.2016.09.007.Search in Google Scholar PubMed

5. Paauw, ND, Lely, AT. Cardiovascular sequels during and after preeclampsia. Adv Exp Med Biol 2018;1065:455–70. https://doi.org/10.1007/978-3-319-77932-4_28.Search in Google Scholar PubMed

6. Newman, MG, Robichaux, AG, Stedman, CM, Jaekle, RK, Fontenot, MT, Dotson, T, et al.. Perinatal outcomes in preeclampsia that is complicated by massive proteinuria. Am J Obstet Gynecol 2003;188:264–8. https://doi.org/10.1067/mob.2003.84.Search in Google Scholar PubMed

7. Nischintha, S, Pallavee, P, Ghose, S. Correlation between 24-h urine protein, spot urine protein/creatinine ratio, and serum uric acid and their association with fetomaternal outcomes in preeclamptic women. J Nat Sci Biol Med 2014;5:255–60. https://doi.org/10.4103/0976-9668.136151.Search in Google Scholar PubMed PubMed Central

8. Bramham, K, Poli-de-Figueiredo, CE, Seed, PT, Briley, AL, Poston, L, Shennan, AH, et al.. Association of proteinuria threshold in pre-eclampsia with maternal and perinatal outcomes: a nested case control cohort of high risk women. PLoS One 2013;8:e76083. https://doi.org/10.1371/journal.pone.0076083.Search in Google Scholar PubMed PubMed Central

9. Keogh, A, Macdonald, P, Harvison, A, Richens, D, Mundy, J, Spratt, P. Initial steroid-free versus steroid-based maintenance therapy and steroid withdrawal after heart transplantation: two views of the steroid question. J Heart Lung Transplant 1992;11:421–7.Search in Google Scholar

10. Tzur, Y, Rimon, E, Geva, G, Herzlich, J, Kupferminc, MJ. Progression from isolated gestational proteinuria to preeclampsia with severe features. Acta Obstet Gynecol Scand 2021;100:1620–6. https://doi.org/10.1111/aogs.14198.Search in Google Scholar PubMed

11. Lei, T, Qiu, T, Liao, W, Li, K, Lai, X, Huang, H, et al.. Proteinuria may be an indicator of adverse pregnancy outcomes in patients with preeclampsia: a retrospective study. Reprod Biol Endocrinol 2021;19:71. https://doi.org/10.1186/s12958-021-00751-y.Search in Google Scholar PubMed PubMed Central

12. Morikawa, M, Mayama, M, Saito, Y, Akabane-Nakagawa, K, Umazume, T, Chiba, K, et al.. Hypoproteinemia as a parameter of poor perinatal/neonatal outcomes in women with preeclampsia diagnosed as hypertension plus proteinuria. Pregnancy Hypertens 2020;21:111–7. https://doi.org/10.1016/j.preghy.2020.05.012.Search in Google Scholar PubMed

13. Payne, BA, Hutcheon, JA, Ansermino, JM, Hall, DR, Bhutta, ZA, Bhutta, SZ, et al.. A risk prediction model for the assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings: the miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) multi-country prospective cohort study. PLoS Med 2014;11:e1001589. https://doi.org/10.1371/journal.pmed.1001589.Search in Google Scholar PubMed PubMed Central

14. Salazar Garcia, MD, Mobley, Y, Henson, J, Davies, M, Skariah, A, Dambaeva, S, et al.. Early pregnancy immune biomarkers in peripheral blood may predict preeclampsia. J Reprod Immunol 2018;125:25–31. https://doi.org/10.1016/j.jri.2017.10.048.Search in Google Scholar PubMed

15. Uzun Cilingir, I, Varol, F, Gurkan, H, Sutcu, H, Atli, E, Eker, D, et al.. Placental and serum levels of human Klotho in severe preeclampsia: a potential sensitive biomarker. Placenta 2019;85:49–55. https://doi.org/10.1016/j.placenta.2019.08.084.Search in Google Scholar PubMed

16. Lv, Y, Lu, C, Ji, X, Miao, Z, Long, W, Ding, H, et al.. Roles of microRNAs in preeclampsia. J Cell Physiol 2019;234:1052–61. https://doi.org/10.1002/jcp.27291.Search in Google Scholar PubMed

17. Cubro, H, Nath, KA, Suvakov, S, Garcia-Valencia, O, Parashuram, S, White, WM, et al.. Mechanisms of vascular dysfunction in the interleukin-10-deficient murine model of preeclampsia indicate nitric oxide dysregulation. Kidney Int 2021;99:646–56. https://doi.org/10.1016/j.kint.2020.09.034.Search in Google Scholar PubMed PubMed Central

18. Winger, EE, Reed, JL, Ji, X. First trimester PBMC microRNA predicts adverse pregnancy outcome. Am J Reprod Immunol 2014;72:515–26. https://doi.org/10.1111/aji.12287.Search in Google Scholar PubMed

19. Winger, EE, Reed, JL, Ji, X. First-trimester maternal cell microRNA is a superior pregnancy marker to immunological testing for predicting adverse pregnancy outcome. J Reprod Immunol 2015;110:22–35. https://doi.org/10.1016/j.jri.2015.03.005.Search in Google Scholar PubMed

20. Caldeira-Dias, M, Luizon, MR, Deffune, E, Tanus-Santos, JE, Freire, PP, Carvalho, RF, et al.. Preeclamptic plasma stimulates the expression of miRNAs, leading to a decrease in endothelin-1 production in endothelial cells. Pregnancy Hypertens 2018;12:75–81. https://doi.org/10.1016/j.preghy.2018.03.001.Search in Google Scholar PubMed

21. Zha, W, Guan, S, Liu, N, Li, Y, Tian, Y, Chen, Y, et al.. Let-7a inhibits Bcl-xl and YAP1 expression to induce apoptosis of trophoblast cells in early-onset severe preeclampsia. Sci Total Environ 2020;745:139919. https://doi.org/10.1016/j.scitotenv.2020.139919.Search in Google Scholar PubMed

22. Wang, D, Liu, N, Tian, Y, Li, Y, Shen, X, Chen, Y, et al.. Expression profile of Let-7s in peripheral blood mononuclear cells of normal and severe preeclampsia pregnant women. Exp Mol Pathol 2019;110:104263. https://doi.org/10.1016/j.yexmp.2019.104263.Search in Google Scholar PubMed

23. Yang, Q, Lu, J, Wang, S, Li, H, Ge, Q, Lu, Z. Application of next-generation sequencing technology to profile the circulating microRNAs in the serum of preeclampsia versus normal pregnant women. Clin Chim Acta 2011;412:2167–73. https://doi.org/10.1016/j.cca.2011.07.029.Search in Google Scholar PubMed

24. Shokrzadeh, N, Alivand, MR, Abedelahi, A, Hessam Shariati, MB, Niknafs, B. Calcitonin administration improves endometrial receptivity via regulation of LIF, Muc-1 and microRNA Let-7a in mice. J Cell Physiol 2019;234:12989–3000. https://doi.org/10.1002/jcp.27969.Search in Google Scholar PubMed

25. Murphy, SP, Tayade, C, Ashkar, AA, Hatta, K, Zhang, J, Croy, BA. Interferon gamma in successful pregnancies. Biol Reprod 2009;80:848–59. https://doi.org/10.1095/biolreprod.108.073353.Search in Google Scholar PubMed PubMed Central

26. Taylor, BD, Ness, RB, Klebanoff, MA, Zoh, R, Bass, D, Hougaard, DM, et al.. First and second trimester immune biomarkers in preeclamptic and normotensive women. Pregnancy Hypertens 2016;6:388–93. https://doi.org/10.1016/j.preghy.2016.09.002.Search in Google Scholar PubMed PubMed Central

27. Liu, X, Hu, Y, Liu, X, Zheng, Y, Luo, M, Liu, W, et al.. EPHB4, a down stream target of IFN-gamma/STAT1 signal pathway, regulates endothelial activation possibly contributing to the development of preeclampsia. Am J Reprod Immunol 2016;76:307–17. https://doi.org/10.1111/aji.12555.Search in Google Scholar PubMed

28. Qin, S, Zhang, Y, Zhang, J, Tian, F, Sun, L, He, X, et al.. SPRY4 regulates trophoblast proliferation and apoptosis via regulating IFN-gamma-induced STAT1 expression and activation in recurrent miscarriage. Am J Reprod Immunol 2020;83:e13234. https://doi.org/10.1111/aji.13234.Search in Google Scholar PubMed

29. Gottardi, E, Lecarpentier, E, Villette, C, Berman, A, Redel, D, Tsatsaris, V, et al.. Preeclampsia before 26 weeks of gestation: obstetrical prognosis for the subsequent pregnancy. J Gynecol Obstet Hum Reprod 2021;50:102000. https://doi.org/10.1016/j.jogoh.2020.102000.Search in Google Scholar PubMed

30. Takahashi, N, Li, F, Fushima, T, Oyanagi, G, Sato, E, Oe, Y, et al.. Vitamin B3 nicotinamide: a promising candidate for treating preeclampsia and improving fetal growth. Tohoku J Exp Med 2018;244:243–8. https://doi.org/10.1620/tjem.244.243.Search in Google Scholar PubMed PubMed Central

31. Kumar, A, Begum, N, Prasad, S, Agarwal, S, Sharma, S. IL-10, TNF-alpha & IFN-gamma: potential early biomarkers for preeclampsia. Cell Immunol 2013;283:70–4. https://doi.org/10.1016/j.cellimm.2013.06.012.Search in Google Scholar PubMed

32. Rorman, E, Freud, A, Wainstock, T, Sheiner, E. Maternal preeclampsia and long-term infectious morbidity in the offspring – a population based cohort analysis. Pregnancy Hypertens 2020;21:30–4. https://doi.org/10.1016/j.preghy.2020.04.010.Search in Google Scholar PubMed

33. Wang, X, Gao, H. Prevention of preeclampsia in high-risk patients with low-molecular-weight heparin: a meta-analysis. J Matern Fetal Neonatal Med 2020;33:2202–8. https://doi.org/10.1080/14767058.2018.1543656.Search in Google Scholar PubMed

34. Yang, X, Yang, J, Liang, X, Chen, Q, Jiang, S, Liu, H, et al.. Landscape of dysregulated placental RNA editing associated with preeclampsia. Hypertension 2020;75:1532–41. https://doi.org/10.1161/hypertensionaha.120.14756.Search in Google Scholar PubMed

35. Akbar, MIA, Yoseph, D-A, Bachnas, MA, Dachlan, EG, Dekker, GA, et al.. Magnesium intoxication in women with preeclampsia with severe features treated with magnesium sulfate. Hypertens Pregnancy 2020;39:221–7. https://doi.org/10.1080/10641955.2020.1754851.Search in Google Scholar PubMed

36. Kedar Sade, E, Wainstock, T, Tsumi, E, Sheiner, E. Prenatal exposure to preeclampsia and long-term ophthalmic morbidity of the offspring. J Clin Med 2020;9. https://doi.org/10.3390/jcm9051271.Search in Google Scholar PubMed PubMed Central

37. Wu, A, Hu, Y, Xu, Y, Xu, J, Wang, X, Cai, A, et al.. Methyltransferase-like 3-mediated m6A methylation of Hsa_circ_0058493 accelerates hepatocellular carcinoma progression by binding to YTH domain-containing protein 1. Front Cell Dev Biol 2021;9:762588. https://doi.org/10.3389/fcell.2021.762588.Search in Google Scholar PubMed PubMed Central

38. Huang, SJ, Chen, CP, Buchwalder, L, Yu, YC, Piao, L, Huang, CY, et al.. Regulation of CX3CL1 expression in human first-trimester decidual cells: implications for preeclampsia. Reprod Sci 2019;26:1256–65. https://doi.org/10.1177/1933719118815592.Search in Google Scholar PubMed PubMed Central

39. Sandrim, VC, Diniz, S, Eleuterio, NM, Gomes, KB, Dusse, LMS, Cavalli, RC. Higher levels of circulating TIMP-4 in preeclampsia is strongly associated with clinical parameters and microRNA. Clin Exp Hypertens 2018;40:609–12. https://doi.org/10.1080/10641963.2017.1411499.Search in Google Scholar PubMed

40. Fuso, P, Di Salvatore, M, Santonocito, C, Guarino, D, Autilio, C, Mule, A, et al.. Let-7a-5p, miR-100-5p, miR-101-3p, and miR-199a-3p hyperexpression as potential predictive biomarkers in early breast cancer patients. J Personalized Med 2021:11. https://doi.org/10.3390/jpm11080816.Search in Google Scholar PubMed PubMed Central

Received: 2021-03-24
Accepted: 2022-04-03
Published Online: 2022-05-23

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