THE ROLE OF RECEPTORS OF INNATE IMMUNITY IN THE PATHOGENESIS OF ASSOCIATED WITH PREMATURE RUPTURE OF MEMBRANES PRETERM LABOR
DOI:
https://doi.org/10.11603/24116-4944.2019.1.10187Keywords:
preterm labor, premature rupture of the fetal membranes, gene transcription activityAbstract
The aim of the study – to develop a method for predicting the development of premature rupture of membranes (PRM) in preterm labor (PTL) based on the results of determining the level of mRNA of TLR2 and TLR4 genes at the local level and hematological parameters of the level of endogenous intoxication.
Materials and Methods. We examined 80 women with PRM in the gestation period of 26–34 weeks (main group) and 50 pregnant women with a physiological course of pregnancy and term labor without complications (control group). For the analysis of transcriptional activity of genes of innate immunity TLR2 and TLR4 in the placenta and fetal membranes, the method of real-time reverse transcriptase polymerase chain reaction was used CFX96 ™ Real-Time PCR Detection Systems amplificator (Bio-RadLaboratories, Inc., USA) and Luminaris HiGreen Fluorescein qPCR MasterMix reagent kit (ThermoScientific, USA).
Results and Discussion. The average age of the examined women was (28.14±6.43) years. The average period of occurrence of PRM in the main group of the study was (31.79±2.06) weeks, the length of the anhydrous period had a wide range and averaged 90.12 hours (from 9 to 313 hours). The range of all obtained values of the relative normalized expression of mRNA of the TLR2 gene in the placenta was (0.79–163.44) (median – 31.06), in fetal membranes – 1.1–126.06 (median – 10.22). The range of all obtained values of the relative normalized expression of the mRNA of the TLR4 gene was lower than the TLR2 in the placenta and was 0.39–43.85 (median – 7.74) and higher in the fetal membranes – 0.18–216.01 (median – 40.04). At 33–34 weeks of the onset of PRM, the expression level of TLR4 in the fetal membranes was 53.53 times more compared to healthy women with physiological pregnancy and labor, at 31–32 weeks – 24.77 times, respectively. The most sensitive leukocyte indexes for assessing the degree of development of endogenous intoxication in pregnant women with preterm labor were NLR and the leukocyte intoxication index (LII) of Kalf-Kalif. In newborns – LII Kalf-Kalif and NLR during hospitalization exceeded the norm by almost 2 times and amounted to respectively, (6.12±2.57), when discharged after labor, against the background of the use of antibacterial therapy – (3.25±1.28).
Conclusions. A marked increased expression of TLR2 and TLR4 is observed in the tissue of the placenta and fetal membranes of women with PRM and PTL in the 26–34 weeks of gestation. An increase in the transcriptional activity of the components of innate immunity is a factor in the implementation of intrauterine and intra-amniotic infection and is an immunological component of the development of miscarriage associated with PRM. The main markers of the degree of activity of the inflammatory process and the severity of endogenous intoxication in preterm labor against the background of PRM in pregnant women are total leukocyte count, LII Kalf-Kalif and NLR.
References
Cho, H.Y., Jung, I., Kwon, J.Y., Kim, S.J., Park, Y.W., & Kim, Y.H. (2017). The Delta Neutrophil Index as a predictive marker of histological chorioamnionitis in patients with preterm premature rupture of membranes: A retrospective study. Plos One, DOI:10.1371/ journal. pone.0173382.
Tchirikov, M.N., Schlabritz-Loutsevitch, J., Maher, J., Buchmann, Y., Naberezhnev, A., Winarno S., & Seliger, G. (2017). Mid-trimester preterm premature rupture of membranes (PPROM): etiology, diagnosis, classification, international recommendations of treatment options and outcome. J. Perinat. Med., 46(5), 465-488. DOI: https://doi.org/10.1515/jpm-2017-0027
Musilova, I., Kutová, R., Pliskova, L., Stepan, M., & Menon, R.
(2015). Intraamniotic inflammation in women with preterm prelabour rupture of membranes. Plos One. doi: 10.1186/s13104-016-2335-5.
Forget, P., Khalifa, C., Defour, J.-P., Latinne, D., Van Pel, M.-C., & Kock, M.D. (2017). What is the normal value of the neutrophil-to-lymphocyte ratio? BMC Research Notes. doi: 10.1186/s13104-016-2335-5. DOI: https://doi.org/10.1186/s13104-016-2335-5
Bukowski, R., Sadovsky, Y., Goodarzi, H., Zhang, H., & Biggio, J.R. (2017). Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface. Peer J., 5, e3685. doi: 10.7717/peerj.3685. DOI: https://doi.org/10.7717/peerj.3685
Lashkari, B.S., Shahana S., & Anumba, D.O. (2015). Toll-like receptor 2 and 4 expression in the pregnant and non-pregnant human uterine cervix. Journal of Reproductive Immunology, 107, 43-51. doi: 10.1016/j.jri.2014.10.001. DOI: https://doi.org/10.1016/j.jri.2014.10.001
Amirchaghmaghi, E., Taghavi, S.A., Shapouri, F., Saeidi, S.,
Rezaei, A., & Aflatoonian, R. (2013). The role of toll like receptors in pregnancy. International Journal of Fertility and Sterility, 7 (3), 147-154.
Koga, K., & Mor, G. (2011). Toll-like receptors at the maternal-fetal interface in normal pregnancy and pregnancy disorders. American Journal of Reproductive Immunology, 63 (6), 587-600.
FIGO Working Group on Good Clinical Practice in Maternal-Fetal Medicine. (2019). Good clinical practice advice: Prediction of preterm labor and preterm premature rupture of membranes. Int. J. Gynaecol. Obstet., 144 (3), 340-346. doi: 10.1002/ijgo.12744. DOI: https://doi.org/10.1002/ijgo.12744
Romero, R., Dey, S.K., & Fisher, S.J. (2014). Preterm labor: One syndrome, many сauses. Science, 345 (6198), 760-765. doi:10.1126/science.1251816. DOI: https://doi.org/10.1126/science.1251816
Lіubomyrska, K.S. (2018). Imunohenetychni chynnyky rozvytku peredchasnoho rozryvu plodovykh obolonok pry nedonoshenii vahitnosti v Zaporizkii oblasti [Immunogenic factors of development of premature rupture of membranes in preterm pregnancies in Zaporizhzhia region]. Patolohiia – Pathology, 3, s.309-318 [in Ukrainian].
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