Expression patterns of maternal and fetal tissue and exosomal microRNAs during pre-induction of labor (pilot study)

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Abstract

Successful preparation of the female body for childbirth, carried out through various mechanisms of labor initiation and activities aimed at early delivery, is necessary to reduce obstetric and neonatal complications. These mechanisms, which combine the inflammatory response in the myometrium, fetal signaling, and physiological aging of membranes, are based on processes and signaling pathways. Coordinated regulation of these processes is performed using microRNAs (miRNAs).

Objective: This study aimed to investigate the expression of maternal and fetal tissues and exosomal miRNAs as signaling molecules for the initiation of labor during cervical ripening.

Materials and methods: This pilot study assessed maternal and fetal tissue and exosomal miRNA expression using quantitative real-time reverse transcription-PCR in 22 pregnant women divided into two cohorts: «labor without pre-induction» (cohort I, n=10) and «pre-induction of labor» (cohort II, n=12). Cohort I was further divided into two groups: pregnant women with spontaneous labor (group Ia, n=5) and pregnant women who underwent a planned cesarean section before the onset of labor (group Ib, n=5). Cohort II included pregnant women with a positive response to pre-induction of labor (group IIa, n=5) and pregnant women who did not achieve this effect (group IIb, n=7).

Results: The study found that the initial level of exosomal miR-181a-5p in the blood plasma before the pre-induction of labor was significantly different (p = 0.03) in pregnant women with a good response (cervical ripening and onset of labor) compared to those with no response. The level of exosomal miR-92a-3p in umbilical cord blood was higher than that in maternal blood before pre-induction (p=0.009). The expression of miR-454-3p and miR-548g-5p was detected only in umbilical cord blood samples, indicating their fetal origin. A pairwise comparison between the groups revealed a significantly higher level of let-7b-5p expression in the membranes in the successful pre-induction group than in the planned cesarean section group (p=0.02) and the group with no effect from pre-induction of labor (p=0.01). Similarly, in the myometrium, the expression of let-7b-5p was significantly higher in the successful pre-induction group than in the planned cesarean section group (p = 0.05).

Conclusion: The identified differences in the expression of tissue and exosomal miRNAs may be due to the highly coordinated regulation of different signaling pathways and the corresponding target genes involved in the mechanism of communication between the maternal and fetal compartments. This provides a basis for further research using larger cohorts of pregnant women.

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About the authors

Asiyat R. Gaidarova

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Author for correspondence.
Email: a_gaydarova@oparina4.ru
ORCID iD: 0000-0003-1415-3318

PhD Student

Russian Federation, 117997, Moscow, Ac. Oparina str., 4

Vladislava A. Gusar

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: v_gusar@oparina4.ru
ORCID iD: 0000-0003-3990-6224

PhD, Senior Researcher at the Laboratory of Applied Transcriptomics of the Department of Systems Biology in Reproduction

Russian Federation, 117997, Moscow, Ac. Oparina str., 4

Vitaliy V. Chagovets

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: v_chagovets@oparina4.ru
ORCID iD: 0000-0002-5120-376X

PhD, Head of the Laboratory of Metabolomics and Bioinformatics

Russian Federation, 117997, Moscow, Ac. Oparina str., 4

Natalia E. Kan

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: kan-med@mail.ru
ORCID iD: 0000-0001-5087-5946

Professor, Dr.Med. Sci., Deputy Director for Science

Russian Federation, 117997, Moscow, Ac. Oparina str., 4

Irina V. Edilberg

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Email: i_edilberg@oparina4.ru
ORCID iD: 0000-0003-4194-8730

PhD Student

Russian Federation, 117997, Moscow, Ac. Oparina str., 4; 119991, Moscow, Trubetskaya str., 8-2

Oleg R. Baev

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Email: o_baev@oparina4.ru
ORCID iD: 0000-0001-8572-1971
SPIN-code: 5378-8437
Scopus Author ID: 57008835600
ResearcherId: B-2370-2015

Dr. Med. Sci., Professor, Head of the 1st Maternity Department, Professor of the Department of Obstetrics, Gynecology, Perinatology and Reproductology

Russian Federation, 117997, Moscow, Ac. Oparina str., 4; 119991, Moscow, Trubetskaya str., 8-2

References

  1. Saucedo A.M., Cahill A.G. Evidence-based approaches to labor induction. Obstet. Gynecol. Surv. 2023; 78(3): 171-83. https://dx.doi.org/10.1097/OGX.0000000000001110.
  2. Marconi A.M. Recent advances in the induction of labor. F1000Res. 2019; 8: F1000 Faculty Rev-1829.2019. https://dx.doi.org/10.12688/f1000research.17587.1.
  3. Российское общество акушеров-гинекологов (РОАГ). Клинические рекомендации "Неудачная попытка стимуляции родов (подготовка шейки матки к родам и родовозбуждение)". 2021. [Russian Society of Obstetricians and Gynecologists. Clinical guidelines "Failed attempt at labor stimulation (cervical preparation and labor induction)". 2021. (in Russian)]. Available at: https://roag-portal.ru/recommendations_obstetrics
  4. Guarnieri D.J., DiLeone R.J. MicroRNAs: a new class of gene regulators. Ann. Med. 2008; 40(3): 197-208. https://dx.doi.org/10.1080/07853890701771823.
  5. Tang Y., Ji H., Liu H., Gu W., Li X., Peng T. Identification and functional analysis of microRNA in myometrium tissue from spontaneous preterm labor. Int. J.Clin. Exp. Pathol. 2015; 8(10): 12811-9.
  6. Williams K.C., Renthal N.E., Gerard R.D., Mendelson C.R. The microRNA (miR)-199a/214 cluster mediates opposing effects of progesterone and estrogen on uterine contractility during pregnancy and labor. Mol. Endocrinol. (Baltimore). 2012; 26(11): 1857-67. https://dx.doi.org/10.1210/me.2012-1199.
  7. Renthal N.E., Chen C.-C., Williams K.C., Gerard R.D., Prange-Kiel J., Mendelson C.R. miR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and contractility during pregnancy and labor. Proc. Natl. Acad. Sci. USA. 2010; 107(48): 20828-33. https://dx.doi.org/10.1073/pnas.1008301107.
  8. Sanders A.P., Burris H.H., Just A.C., Motta V., Svensson K., Mercado-Garcia A. et al. microRNA expression in the cervix during pregnancy is associated with length of gestation. Epigenetics. 2015; 10(3): 221-8. https://dx.doi.org/ 10.1080/15592294.2015.1006498.
  9. Williams K.C., Renthal N.E., Condon J.C., Gerard R.D., Mendelson C.R. MicroRNA-200a serves a key role in the decline of progesterone receptor function leading to term and preterm labor. Proc. Natl. Acad. Sci. USA. 2012; 109(19): 7529-34. https://dx.doi.org/10.1073/pnas.1200650109.
  10. Bracken C.P., Gregory P.A., Kolesnikoff N., Bert A.G., Wang J., Shannon M.F. et al. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Res. 2008; 68(19): 7846-54. https://dx.doi.org/10.1158/0008-5472.CAN-08-1942.
  11. Sun X., Sit A., Feinberg M.W. Role of miR-181 family in regulating vascular inflammation and immunity. Trends Cardiovasc. Med. 2014; 24(3): 105-12. https://dx.doi.org/10.1016/j.tcm.2013.09.002.
  12. Gao L., Wang G., Liu W.N., Kinser H., Franco H.L., Mendelson C.R. Reciprocal feedback between miR-181a and E2/ERα in myometrium enhances inflammation leading to labor. J. Clin. Endocrinol. Metabo. 2016; 101(10): 3646-56. https://dx.doi.org/10.1210/jc.2016-2078.
  13. Li H., Zhou J., Wei X., Chen R., Geng J., Zheng R. et al. miR-144 and targets, c-fos and cyclooxygenase-2 (COX2), modulate synthesis of PGE2 in the amnion during pregnancy and labor. Sci. Rep. 2016; 6: 27914. https://dx.doi.org/10.1038/srep27914.
  14. Kim S.Y., Romero R., Tarca A.L., Bhatti G., Lee J., Chaiworapongsa T. et al. miR-143 regulation of prostaglandin-endoperoxidase synthase 2 in the amnion: implications for human parturition at term. PloS One. 2011; 6(9): e24131. https://dx.doi.org/10.1371/journal.pone.0024131.
  15. Montenegro D., Romero R., Kim S.S., Tarca A.L., Draghici S., Kusanovic J.P. et al. Expression patterns of microRNAs in the chorioamniotic membranes: a role for microRNAs in human pregnancy and parturition. J. Pathol. 2009; 217(1): 113-21. https://dx.doi.org/10.1002/path.2463.
  16. Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001; 25(4): 402-8. https://dx.doi.org/10.1006/meth.2001.1262.
  17. Ilekis J.V., Tsilou E., Fisher S., Abrahams V.M., Soares M.J., Cross J.C. et al. Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Am. J. Obstet. Gynecol. 2016; 215(1, Suppl.): S1-46. https://dx.doi.org/10.1016/j.ajog.2016.03.001.
  18. Gurung S., Perocheau D., Touramanidou L., Baruteau J. The exosome journey: from biogenesis to uptake and intracellular signalling. Cell Commun. Signal. 2021; 19(1): 47. https://dx.doi.org/10.1186/s12964-021-00730-1.
  19. Jadli A.S., Ballasy N., Edalat P., Patel V.B. Inside(sight) of tiny communicator: exosome biogenesis, secretion, and uptake. Mol. Cell. Biochem. 2020; 467(1-2): 77-94. https://dx.doiorg/10.1007/s11010-020-03703-z.
  20. Simons M., Raposo G. Exosomes--vesicular carriers for intercellular communication. Curr. Opin. Cell Biol. 2009; 21(4): 575-81. https://dx.doi.org/10.1016/j.ceb.2009.03.007.
  21. Robbins P.D., Morelli A.E. Regulation of immune responses by extracellular vesicles. Nat. Rev. Immunol. 2014; 14(3): 195-208. https://dx.doi.org/10.1038/nri3622.
  22. Menon R., Debnath C., Lai A., Guanzon D., Bhatnagar S., Kshetrapal P.K. et al. Circulating exosomal miRNA profile during term and preterm birth pregnancies: a longitudinal study. Endocrinology. 2019; 160(2): 249-75. https://dx.doi.org/10.1210/en.2018-00836.
  23. Xie W., Li Z., Li M., Xu N., Zhang Y. miR-181a and inflammation: miRNA homeostasis response to inflammatory stimuli in vivo. Biochem. Biophys. Res. Commun. 2013; 430(2): 647-52. https://dx.doi.org/10.1016/j.bbrc.2012.11.097.
  24. Hutchison E.R., Kawamoto E.M., Taub D.D., Lal A., Abdelmohsen K., Zhang Y. et al. Evidence for miR-181 involvement in neuroinflammatory responses of astrocytes. Glia. 2013; 61(7): 1018-28. https://dx.doi.org/10.1002/glia.22483.
  25. Wang L., Bi R., Li L., Zhou K., Yin H. lncRNA ANRIL aggravates the chemoresistance of pancreatic cancer cells to gemcitabine by targeting inhibition of miR-181a and targeting HMGB1-induced autophagy. Aging (Albany NY). 2021; 13(15): 19272-81. https://dx.do.org/ 10.18632/aging.203251.
  26. Han Y., Chen R., Lin Q., Liu Y., Ge W., Cao H. et al. Curcumin improves memory deficits by inhibiting HMGB1-RAGE/TLR4-NF-κB signalling pathway in APPswe/PS1dE9 transgenic mice hippocampus. J. Cell. Mol. Med. 2021; 25(18): 8947-56. https://dx.doi.org/10.1111/jcmm.16855.
  27. Jin J., Menon R. Placental exosomes: A proxy to understand pregnancy complications. Am. J. Rep. Immunol. 2018; 79(5): e12788. https://dx.doi.org/10.1111/aji.12788.
  28. Hadley E.E., Sheller-Miller S., Saade G., Salomon C., Mesiano S., Taylor R.N. et al. Amnion epithelial cell-derived exosomes induce inflammatory changes in uterine cells. Am. J. Obstet. Gynecol. 2018; 219(5): 478. e1-478.e21. https://dx.doi.org/10.1016/j.ajog.2018.08.021.
  29. Menon R., Mesiano S., Taylor R.N. Programmed fetal membrane senescence and exosome-mediated signaling: a mechanism associated with timing of human parturition. Front. Endocrinol. 2017; 8: 196. https://dx.doi.org/10.3389/fendo.2017.00196.
  30. Lee H., Zhang D., Wu J., Otterbein L.E., Jin Y. Lung epithelial cell-derived microvesicles regulate macrophage migration via MicroRNA-17/221-induced integrin β1 recycling. J. Immunol. 2017; 199(4): 1453-64. https://dx.doi.org/10.4049/jimmunol.1700165.
  31. Slattery M.L., Mullany L.E., Sakoda L., Samowitz W.S., Wolff R.K., Stevens J.R. et al. The NF-κB signalling pathway in colorectal cancer: associations between dysregulated gene and miRNA expression. J. Cancer Res. Clin. 2018; 144(2): 269-83. https://dx.doi.org/10.1007/s00432-017-2548-6.
  32. Lee H., Zhang D., Zhu Z., Dela Cruz C.S., Jin Y. Epithelial cell-derived microvesicles activate macrophages and promote inflammation via microvesicle-containing microRNAs. Sci. Rep. 2016; 6: 35250. https://dx.doi.org/10.1038/srep35250.
  33. Renthal N.E., Williams K.C., Mendelson C.R. MicroRNAs--mediators of myometrial contractility during pregnancy and labour. Nat. Rev. Endocrinol. 2013; 9(7): 391-401. https://dx.doi.org/10.1038/nrendo.2013.96.
  34. Ali A., Bouma G.J., Anthony R.V., Winger Q.A. The role of LIN28-let-7-ARID3B pathway in placental development. Int. J. Mol. Sci. 2020; 21(10): 3637. https://dx.doi.org/10.3390/ijms21103637.
  35. Chan H.W., Lappas M., Yee S.W.Y., Vaswani K., Mitchell M.D., Rice G.E. The expression of the let-7 miRNAs and Lin28 signalling pathway in human term gestational tissues. Placenta. 2013; 34(5): 443-8. https://dx.doi.org/10.1016/j.placenta.2013.02.008.
  36. Cook J.R., MacIntyre D.A., Samara E., Kim S.H., Singh N., Johnson M.R. et al. Exogenous oxytocin modulates human myometrial microRNAs. Am. J. Obstet. Gynecol. 2015; 213(1): 65.e1-65.e9. https://dx.doi.org/10.1016/ j.ajog.2015.03.015.
  37. Teng G., Wang W., Dai Y., Wang S., Chu Y., Li J. Let-7b is involved in the inflammation and immune responses associated with Helicobacter pylori infection by targeting Toll-like receptor 4. PloS One. 2013; 8(2): e56709. https://dx.doi.org/10.1371/journal.pone.0056709.
  38. Dai T., Kang X., Yang C., Mei S., Wei S., Guo X. et al. Integrative analysis of miRNA-mRNA in ovarian granulosa cells treated with kisspeptin in tan sheep. Animals (Basel). 2022; 12(21): 2989. https://dx.doi.org/10.3390/ani12212989.
  39. Zhang X.D., Zhang Y.H., Ling Y.H., Liu Y., Cao H.G., Yin Z.J. et al. Characterization and differential expression of microRNAs in the ovaries of pregnant and non-pregnant goats (Capra hircus). BMC Genomics. 2013; 14: 157. https://dx.doi.org/10.1186/1471-2164-14-157.
  40. Bhat-Nakshatri P., Wang G., Collins N.R., Thomson M.J., Geistlinger T.R., Carroll J.S. et al. Estradiol-regulated microRNAs control estradiol response in breast cancer cells. Nucleic Acids Res. 2009; 37(14): 4850-61. https://dx.doi.org/10.1093/nar/gkp500.
  41. Taganov K.D., Boldin M.P., Chang K.-J., Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc. Natl. Acad. Sci. USA. 2006; 103(33): 12481-6. https://dx.doi.org/10.1073/pnas.0605298103.
  42. Mohammad N.S., Nazli R., Zafar H., Fatima S. Effects of lipid based multiple micronutrients supplement on the birth outcome of underweight pre-eclamptic women: A randomized clinical trial. Pak. J. Med. Sci. 2022; 38(1): 219-26. https://dx.doi.org/10.12669/pjms.38.1.4396.

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