Influence of microbial colonization of the endometry on its function and development of hyperproliferative conditions
Abstract
Abstract. The article provides an overview of literary sources that describe research on the microbiome of the endometrium in women of reproductive age. Thus, in many works, data is given indicating that the uterine cavity is not sterile. Various microorganisms can be found on the surface of the endometrium. So far, there is not enough research on microorganisms that can be considered a normal microbiome of the endometrium and its influence on the function and development of hyperproliferative processes of the endometrium in women. Many studies have proven the undoubted role of the uterine microbiome in the development of endometrial hyperplasia and other proliferative diseases. The cited studies indicate that 60 % of examined women with signs of microbial colonization caused by an infection of viral, bacterial, or fungal origin developed endometrial dysfunction, which led to the development of hyperproliferative processes. The study of the microbiocenosis of the uterine cavity in patients of reproductive age with various types of endometrial pathology indicates the role of certain pathogenic microflora in their occurrence. In all cases of atypical proliferation of the endometrium, an increase in the number of anaerobes up to 30 % was found among all isolated microorganisms, in particular, anaerobic bacteria of the genus Bacteroides spp. Representatives of the Enterobacteriaceae family (E. coli) and Gram-positive cocci (staphylococci and streptococci) prevailed among the aerobic flora. The largest spectrum of isolated microorganisms was found in patients with endometrial polyps. Studies of the immune system of the endometrium, which is formed to a greater extent due to the microbiome and directly participates in the cyclic changes of the endometrium, which are necessary for its physiological function during reproduction, are also presented. The immune system of the endometrium participates in the cyclic changes of the endometrium necessary for its physiological function in the process of reproduction. A proven factor is cells of the immune system and proper remodeling of spiral arteries, NK (neutrophil killer), T-lymphocytes and antigen-presenting cells (APC – antigen-presenting cell). A very important factor in the interaction between the gut microbiome and the immune system is the gut mucosa, and from this it can be inferred that similar connections may exist for the endometrium and its microbiome. Further studies of the state of the microbiome of the uterine cavity will allow adding information about its participation in functional processes and the pathogenesis of the development of hyperproliferative endometrial conditions.
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Benner M, Ferwerda G, Joosten I, van der Molen RG. How uterine microbiota might be responsible for a receptive, fertile endometrium. Hum Reprod Update. 2018;24(4):393–415. DOI: https://doi.org/10.1093/humupd/dmy012
Khaskhachykh D, Potapov V. Impact of changes in the vaginal microbiome and chronic endometritis on the initiation of hyperplastic processes of the endometrium in women. USMYJ. 2022; 134 (4): 22–28. DOI: https://doi.org/10.32345/USMYJ.4(134).2022.22-28
Buck VU, Windoffer R, Leube RE, Classen-Linke I. Redistribution of adhering junctions in human endometrial epithelial cells during the implantation window of the menstrual cycle. Histochem Cell Biol. 2012;137(6):777-790. DOI: https://doi.org/10.1007/s00418-012-0929-0
Buck VU, Windoffer R, Leube RE, Classen-Linke I. Redistribution of adhering junctions in human endometrial epithelial cells during the implantation window of the menstrual cycle. Histochem Cell Biol. 2012;137(6):777-790. DOI: https://doi.org/10.1007/s00418-012-0929-0
Dvořan M, Vodička J, Dostál J, Hajdůch M, Džubák P, Pešková M, Pilka R. Implantation and diagnostics of endometrial receptivity. Implantace a diagnostika receptivity endometria. Ceska gynekologie. 2018; 83 (4): 291–298. PMID: 30441961.
Franasiak JM, Scott RT Jr. Reproductive tract microbiome in assisted reproductive technologies. Fertil Steril. 2015; 104 (6): 1364–1371. DOI: https://doi.org/10.1016/j.fertnstert.2015.10.012
Franasiak JM, Scott RT. Endometrial microbiome. Curr Opin Obstet Gynecol. 2017; 29 (3): 146–152. DOI: https://doi.org/10.1097/GCO.0000000000000357
Franasiak JM, Werner MD, Juneau CR, Tao X, Landis J, Zhan Y, Treff NR, Scott RT. Endometrial microbiome at the time of embryo transfer: next-generation sequencing of the 16S ribosomal subunit. J Assist Reprod Genet. 2016; 33 (1): 129–136. DOI: https://doi.org/10.1007/s10815-015-0614-z
Geva-Zatorsky N, Sefik E, Kua L, Pasman L, Tan TG, Ortiz-Lopez A, Yanortsang TB, Yang L, Jupp R, Mathis D, Benoist C, Kasper DL. Mining the Human Gut Microbiota for Immunomodulatory Organisms. Cell. 2017; 168 (5): 928–943. e11. DOI: https://doi.org/10.1016/j.cell.2017.01.022
Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science. 2012; 336 (6086):1268–1273. DOI: https://doi.org/10.1126/science.1223490
Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, Wei D, Goldfarb KC, Santee CA, Lynch SV, Tanoue T, Imaoka A, Itoh K, Takeda K, Umesaki Y, Honda K, Littman DR. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009 Nov 13; 139 (3): 485–98. DOI: https://doi.org/10.1016/j.cell.2009.09.033
Macpherson AJ, de Agüero MG, Ganal-Vonarburg SC. How nutrition and the maternal microbiota shape the neonatal immune system. Nat Rev Immunol. 2017 Aug; 17 (8): 508–517. DOI: https://doi.org/10.1038/nri.2017.58
Miles SM, Hardy BL, Merrell DS. Investigation of the microbiota of the reproductive tract in women undergoing a total hysterectomy and bilateral salpingo-oopherectomy. Fertil Steril. 2017 Mar; 107 (3): 813–820. e1. DOI: https://doi.org/10.1016/j.fertnstert.2016.11.028
Mitchell CM, Haick A, Nkwopara E, Garcia R, Rendi M, Agnew K, Fredricks DN, Eschenbach D. Colonization of the upper genital tract by vaginal bacterial species in nonpregnant women. Am J Obstet Gynecol. 2015 May;2 12 (5): 611. e1-9. DOI: https://doi.org/ 10.1016/j.ajog.2014.11.043
Moore DE, Soules MR, Klein NA, Fujimoto VY, Agnew KJ, Eschenbach DA. Bacteria in the transfer catheter tip influence the live-birth rate after in vitro fertilization. Fertil Steril. 2000 Dec; 74 (6): 1118–24. DOI: https://doi.org/10.1016/s0015-0282(00)01624-1
Moreno I, Franasiak JM. Endometrial microbiota-new player in town. Fertil Steril. 2017 Jul;108(1):32-39. DOI: https://doi.org/ 10.1016/j.fertnstert.2017.05.034. PMID: 28625375.
Postler TS, Ghosh S. Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System. Cell Metab. 2017 Jul 5; 26 (1): 110–130. DOI: https://doi.org/ 10.1016/j.cmet.2017.05.008
Power ML, Quaglieri C, Schulkin J. Reproductive Microbiomes: A New Thread in the Microbial Network. Reprod Sci. 2017 Nov;24 (11): 1482–1492. DOI: https://doi.org/ 10.1177/1933719117698577
Prince AL, Ma J, Kannan PS, Alvarez M, Gisslen T, Harris RA, Sweeney EL, Knox CL, Lambers DS, Jobe AH, Chougnet CA, Kallapur SG, Aagaard KM. The placental membrane microbiome is altered among subjects with spontaneous preterm birth with and without chorioamnionitis. Am J Obstet Gynecol. 2016 May;214 (5): 627. e1-16. DOI: https://doi.org/ 10.1016/j.ajog.2016.01.193
Selman H, Mariani M, Barnocchi N, Mencacci A, Bistoni F, Arena S, Pizzasegale S, Brusco GF, Angelini A. Examination of bacterial contamination at the time of embryo transfer, and its impact on the IVF/pregnancy outcome. J Assist Reprod Genet. 2007 Sep; 24 (9): 395–9. DOI: https://doi.org/ 10.1007/s10815-007-9146-5
Selman H, Mariani M, Barnocchi N, Mencacci A, Bistoni F, Arena S, Pizzasegale S, Brusco GF, Angelini A. Examination of bacterial contamination at the time of embryo transfer, and its impact on the IVF/pregnancy outcome. J Assist Reprod Genet. 2007 Sep; 24 (9): 395–9. DOI: https://doi.org/ 10.1007/s10815-007-9146-5
Swiecki M, Miller HL, Sesti-Costa R, Cella M, Gilfillan S, Colonna M. Microbiota induces tonic CCL2 systemic levels that control pDC trafficking in steady state. Mucosal Immunol. 2017 Jul; 10 (4): 936–945. DOI: https://doi.org/10.1038/mi.2016.99
Khaskhachykh D, Potapov V. Molecular mechanisms of the endometrial hyperplasia of the endometrial therapy on the basis of the study of receptor expression, cell markers of proliferation, differentiation and apoptosis of the endometrial cells in the hormone’s dependent signal path. Grail of Science. 2022; 12–13: 620–623. DOI: https://doi.org/ 10.36074/grail-of-science.29.04.2022
Wira CR, Grant-Tschudy KS, Crane-Godreau MA. Epithelial cells in the female reproductive tract: a central role as sentinels of immune protection. Am J Reprod Immunol. 2005 Feb; 53 (2): 65–76. DOI: https://doi.org/10.1111/j.1600-0897.2004.00248.x
Newton K, Dixit VM. Signaling in innate immunity and inflammation. Cold Spring Harb Perspect Biol. 2012; 4 (3): a006049. DOI: https://doi.org/10.1101/cshperspect.a006049
Tang D, Kang R, Coyne CB, Zeh HJ, Lotze MT. PAMPs and DAMPs: signal 0s that spur autophagy and immunity. Immunol Rev. 2012; 249 (1): 158–175. DOI: https://doi.org/ 10.1111/j.1600-065X.2012.01146.x
Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev. 2009; 22 (2): 240–273. DOI: https://doi.org/10.1128/CMR.00046-08
Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol. 2007;81(1):1-5. DOI: https://doi.org/10.1189/jlb.0306164
Schaefer L. Complexity of danger: the diverse nature of damage-associated molecular patterns. J Biol Chem. 2014; 289 (51): 35237–35245. DOI: https://doi.org/10.1074/jbc.R114.619304
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