ymjЯкутский медицинский журналYakut Medical Journal1813-19052312-1017ЯНЦ КМП10.25789/YMJ.2023.82.02ymj-33Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHВзаимосвязь типа микробиоты и иммунных ресурсов эндометрия бесплодных женщин в фазу имплантационного окнаThe relationship between the microbiota type and immune resources of the endometrium among infertile women in the implantation window phaseПолинаМ. Л.PolinaM. L.

Мирослава Леонидовна Полина, к. м. н., врач-гинеколог, ассистент кафедры

Медицинский институт

Москва

Moscow

polina.ml@mail.ruМихалеваЛ. М.MikhalevaL. M.

Людмила Михайловна Михалева, д. м. н., чл.-корр. РАН, проф., директор НИИ, зав. лаб.

Москва

Moscow

ВитязеваИ. И.VityazevaI. I.

Ирина Ивановна Витязева, д. м. н., зав. отд.

Москва

Moscow

ХамошинаМ. Б.KhamoshinaM. B.

Марина Борисовна Хамошина, д. м. н., проф.

Москва

Moscow

ОрдиянцИ. М.OrdiyantsI. M.

Ирина Михайловна Ордиянц, д. м. н., проф.

Москва

Moscow

ЛебедеваМ. Г.LebedevaM. G.

Марина Георгиевна Лебедева, к. м. н., доцент

Москва

Moscow

ШеленинаЛ. А.SheleninaL. A.

Людмила Александровна Шеленина, врач гинеколог

Москва

Moscow

ЗахароваП. Н.ZakharovaP. N.

Прасковья Николаевна Захарова, аспирант

Якутск

Yakutsk

ДугласН. И.DouglasN. I.

Наталья Ивановна Дуглас, д. м. н., зав. кафедрой

Якутск

Yakutsk

Медицинский центр женского здоровья; Российский ун-т Дружбы народовРоссияMedical Center for Women's Health; Peoples' Friendship University of RussiaRussian FederationНИИ морфологии человекаРоссияResearch Institute of Human MorphologyRussian FederationНациональный медицинский исследовательский центр эндокринологии МЗ РФРоссияNational Medical Research Center of Endocrinology of the Ministry of Health of the Russian FederationRussian FederationМединститут РУДНРоссияMedical Institute of RUDN UniversityRussian FederationГородска\ клинич. б-ца им. Ф.И. Иноземцева Департамента здравоохранения г. МосквыРоссияGorodska\ klinich. F.I. Inozemtsev Medical Center of the Moscow City Department of HealthRussian FederationМединститут Северо-Восточного федеральн. ун-та им. М.К. Аммосова»РоссияMedical Institute of the North-Eastern Federal District. M.K. Ammosov University"Russian FederationМединститут СВФУ им. М.К. АммосоваРоссияMedical Institute of the North-Eastern Federal District. M.K. Ammosov University"Russian Federation20230302202502813Copyright © Полина М.Л., Михалева Л.М., Витязева И.И., Хамошина М.Б., Ордиянц И.М., Лебедева М.Г., Шеленина Л.А., Захарова П.Н., Дуглас Н.И., 20252025Полина М.Л., Михалева Л.М., Витязева И.И., Хамошина М.Б., Ордиянц И.М., Лебедева М.Г., Шеленина Л.А., Захарова П.Н., Дуглас Н.И.Polina M.L., Mikhaleva L.M., Vityazeva I.I., Khamoshina M.B., Ordiyants I.M., Lebedeva M.G., Shelenina L.A., Zakharova P.N., Douglas N.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://ymj.elpub.ru/jour/article/view/33

   Изучены особенности микробиоты и иммунного профиля эндометрия женщин с бесплодием различного генеза в период «имплантационного окна». Выявлены фенотипы эндометрия, отличные по иммунному профилю и профилю микробиоты внутри каждой группы (с бесплодием неясного генеза, трубно-перитонеального генеза, хроническим эндометритом, «тонким» эндометрием): «нормальный», диспластический, хронического воспаления. При фенотипе хронического эндометрита выявлено достоверное преобладание цитокинов провоспалительного профиля Th1/Th1 в присутствии дисбиотичного типа микробиоты. Особенности диспластического фенотипа эндометрия заключаются в «бедном» иммунном ответе (цитокинов, хемокинов, факторов роста) на фоне выраженной фибротической трансформации. Представления о фенотипе эндометрия (нормальный, диспластический, хроническое воспаление) выступают критерием готовности к имплантации бластоцисты.

   The features of the microbiota and the immune profile of the endometrium of women with infertility of different genesis during the "implantation window" period have been studied. Endometrial phenotypes different in immune profile and microbiota profile within each group were identified (with infertility of unclear genesis, tube-peritoneal genesis, chronic endometritis, "thin" endometrium): "normal," dysplastic, chronic inflammation. The phenotype of chronic endometritis is revealed a significant predominance of cytokines of the pro-inflammatory Th1/Th1 profile in the presence of a dysbiotic microbiota type. The features of the dysplastic endometrial phenotype consist in a "poor" immune response (cytokines, chemokines, growth factors) against the background of pronounced fibrotic transformation. Ideas about the endometrial phenotype (normal, dysplastic, chronic inflammation) are a criterion for readiness for blastocyst implantation.

бесплодиепериод «имплантационного окна»хронический эндометритиммуногистохимическое исследованиемолекулярный фенотиплактобациллярный и дисбиотический типы микробиотыinfertilitythe period of the "implantation window"chronic endometritisimmunohistochemical studymolecular phenotypelactobacillar and dysbiotic types of microbiotaReferencesChen P., Yang M., Wang Y. et al. Aging endometrium in young women: Molecular classification of endometrial aging-based markers in women younger than 35 years with recurrent implantation failure // J Assist Reprod Genet. 2022. Vol. 39. N9. P.2143-2151. doi: 10.1007/s10815-022-02578-xChen P., Yang M., Wang Y. et al. Aging endometrium in young women: Molecular classification of endometrial aging-based markers in women younger than 35 years with recurrent implantation failure // J Assist Reprod Genet. 2022. Vol. 39. N9. P.2143-2151. doi: 10.1007/s10815-022-02578-xChen W., Wei K., He X. et al. Identification of Uterine Microbiota in Infertile Women Receiving in vitro Fertilization with and Without Chronic Endometritis // Front. Cell Dev. Biol. 2021. Vol. 9. P. 693267. doi: 10.3389/fcell.2021.693267Chen W., Wei K., He X. et al. Identification of Uterine Microbiota in Infertile Women Receiving in vitro Fertilization with and Without Chronic Endometritis // Front. Cell Dev. Biol. 2021. Vol. 9. P. 693267. doi: 10.3389/fcell.2021.693267Cicinelli E., Matteo M., Tinelli R. et al.: Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy // Hum Reprod. 2015. Vol. 30. P.323–330.Cicinelli E., Matteo M., Tinelli R. et al.: Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy // Hum Reprod. 2015. Vol. 30. P.323–330.Drizi A., Djokovic D., Laganà A.S., van Herendael B. Impaired inflammatory state of the endometrium: a multifaceted approach to endometrial inflammation. Current insights and future directions // Prz Menopauz. 2020. Vol. 19. P. 90-100.Drizi A., Djokovic D., Laganà A.S., van Herendael B. Impaired inflammatory state of the endometrium: a multifaceted approach to endometrial inflammation. Current insights and future directions // Prz Menopauz. 2020. Vol. 19. P. 90-100.Franasiak J.M., Scott R.T. Reproductive tract microbiome in assisted reproductive technologies // Fertil. Steril. 2015. Vol. 104. P. 1364–1371. doi: 10.1016/j.fertnstert.2015.10.012Franasiak J.M., Scott R.T. Reproductive tract microbiome in assisted reproductive technologies // Fertil. Steril. 2015. Vol. 104. P. 1364–1371. doi: 10.1016/j.fertnstert.2015.10.012Gellersen B., Brosens J.J. Cyclic decidualization of the human endometrium in reproductive health and failure // Endocr Rev. 2014. Vol. 35. P. 851–905. doi: 10.1210/er.2014-1045Gellersen B., Brosens J.J. Cyclic decidualization of the human endometrium in reproductive health and failure // Endocr Rev. 2014. Vol. 35. P. 851–905. doi: 10.1210/er.2014-1045Haggerty C.L., Hillier S.L., Bass D.C. et al.: Bacterial Vaginosis and Anaerobic Bacteria Are Associated with Endometritis // Clinical Infectious Diseases. 2004. Vol. 39. P.990–995.Haggerty C.L., Hillier S.L., Bass D.C. et al.: Bacterial Vaginosis and Anaerobic Bacteria Are Associated with Endometritis // Clinical Infectious Diseases. 2004. Vol. 39. P.990–995.Hooper L.V., Littman D.R., Macpherson A.J. Interactions between the microbiota and the immune system // Science. 2012. Vol. 336. N 6086. P. 1268–1273. doi: 10.1126/science.1223490.Hooper L.V., Littman D.R., Macpherson A.J. Interactions between the microbiota and the immune system // Science. 2012. Vol. 336. N 6086. P. 1268–1273. doi: 10.1126/science.1223490.Huang J., Qin H., Yang Y. et al. A Comparison of Transcriptomic Profiles in Endometrium During Window of Implantation Between Women With Unexplained Recurrent Implantation Failure and Recurrent Miscarriage // Reproduction. 2017. Vol. 153. N 6. P. 749–58. doi: 10.1530/REP-16-0574Huang J., Qin H., Yang Y. et al. A Comparison of Transcriptomic Profiles in Endometrium During Window of Implantation Between Women With Unexplained Recurrent Implantation Failure and Recurrent Miscarriage // Reproduction. 2017. Vol. 153. N 6. P. 749–58. doi: 10.1530/REP-16-0574Katz S., Zsiros V., Doczi N., Kiss A.L. Inflammation-induced epithelialto-mesenchymal transition and GM-CSF treatment stimulate mesenteric mesothelial cells to transdifferentiate into macrophages // Inflammation. 2018. P. 825. doi: 10.1007/s10753-018-0825-4Katz S., Zsiros V., Doczi N., Kiss A.L. Inflammation-induced epithelialto-mesenchymal transition and GM-CSF treatment stimulate mesenteric mesothelial cells to transdifferentiate into macrophages // Inflammation. 2018. P. 825. doi: 10.1007/s10753-018-0825-4Kitaya K., Matsubayashi H., Takaya Y. et al.: Live birth rate following oral antibiotic treatment for chronic endometritis in infertile women with repeated implantation failure // Am J Reprod Immunol. 2017. Vol. 78. P.5. doi: 10.1111/aji.12719.Kitaya K., Matsubayashi H., Takaya Y. et al.: Live birth rate following oral antibiotic treatment for chronic endometritis in infertile women with repeated implantation failure // Am J Reprod Immunol. 2017. Vol. 78. P.5. doi: 10.1111/aji.12719.Kyono K., Hashimoto T., Kikuchi S. et al. A pilot study and case reports on endometrial microbiota and pregnancy outcome: An analysis using 16S rRNA gene sequencing among IVF patients, and trial therapeutic intervention for dysbiotic endometrium // Reprod. Med. Biol. 2019. Vol. 18. P.72–82. doi: 10.1002/rmb2.12250.Kyono K., Hashimoto T., Kikuchi S. et al. A pilot study and case reports on endometrial microbiota and pregnancy outcome: An analysis using 16S rRNA gene sequencing among IVF patients, and trial therapeutic intervention for dysbiotic endometrium // Reprod. Med. Biol. 2019. Vol. 18. P.72–82. doi: 10.1002/rmb2.12250.Lédée N., Petitbarat M., Chevrier L. et al. The Uterine Immune Profile May Help Women With Repeated Unexplained Embryo Implantation Failure After In Vitro Fertilization // Am. J. Reprod. Immunol. 2016. Vol. 75. P. 388–401. doi: 10.1111/aji.12483Lédée N., Petitbarat M., Chevrier L. et al. The Uterine Immune Profile May Help Women With Repeated Unexplained Embryo Implantation Failure After In Vitro Fertilization // Am. J. Reprod. Immunol. 2016. Vol. 75. P. 388–401. doi: 10.1111/aji.12483Lessey B.A., Young SL. What exactly is endometrial receptivity? // Fertil Steril. 2019. Vol. 111. P. 611–617.Lessey B.A., Young SL. What exactly is endometrial receptivity? // Fertil Steril. 2019. Vol. 111. P. 611–617.Li X., Cannon A.R., Hammer A.M. et al. IL-23 restoration of Th17 effector function is independent of IL-6 and TGF-β in a mouse model of alcohol and burn injury // J Leukoc Biol. 2017. Vol.102. P.915–23. doi: 10.1189/jlb.3A1216-527RLi X., Cannon A.R., Hammer A.M. et al. IL-23 restoration of Th17 effector function is independent of IL-6 and TGF-β in a mouse model of alcohol and burn injury // J Leukoc Biol. 2017. Vol.102. P.915–23. doi: 10.1189/jlb.3A1216-527ROhara Y., Matsubayashi H., Suzuki Y. et al. Clinical relevance of a newly developed endometrial receptivity test for patients with recurrent implantation failure in Japan // Reprod Med Biol. 2022. Vol.21. P.e12444. doi: 10.1002/rmb2.12444Ohara Y., Matsubayashi H., Suzuki Y. et al. Clinical relevance of a newly developed endometrial receptivity test for patients with recurrent implantation failure in Japan // Reprod Med Biol. 2022. Vol.21. P.e12444. doi: 10.1002/rmb2.12444Paul M.K, Bisht B., Darmawan D.O. et al. Dynamic changes in intracellular ROS levels regulate airway basal stem cell homeostasis through Nrf2-dependent Notch signaling // Cell Stem Cell. 2014. Vol. 15. P. 199–214.Paul M.K, Bisht B., Darmawan D.O. et al. Dynamic changes in intracellular ROS levels regulate airway basal stem cell homeostasis through Nrf2-dependent Notch signaling // Cell Stem Cell. 2014. Vol. 15. P. 199–214.Vannuccini S., Clifton V.L., Fraser I.S. et al. Infertility and reproductive disorders: impact of hormonal and inflammatory mechanisms on pregnancy outcome // Hum Reprod Update. 2016. Vol. 22, N 1. P.104–115. doi: 10.1093/humupd/dmv044.Vannuccini S., Clifton V.L., Fraser I.S. et al. Infertility and reproductive disorders: impact of hormonal and inflammatory mechanisms on pregnancy outcome // Hum Reprod Update. 2016. Vol. 22, N 1. P.104–115. doi: 10.1093/humupd/dmv044.von Hundelshausen P., Agten S.M., Eckardt V. et al. Chemokine interactome mapping enables tailored intervention in acute and chronic inflammation // Sci. Transl. Med. 2017. N 9. P.384. eaah6650. doi: 10.1126/scitranslmed.aah6650von Hundelshausen P., Agten S.M., Eckardt V. et al. Chemokine interactome mapping enables tailored intervention in acute and chronic inflammation // Sci. Transl. Med. 2017. N 9. P.384. eaah6650. doi: 10.1126/scitranslmed.aah6650Yen M., Donma O., Yildizfer F. et al. Association of fetuin A, adiponectin, interleukin 10 and total antioxidant capacity with IVF outcomes // Iran. J. Reprod. Med. 2014. V. 12. P. 747–754.Yen M., Donma O., Yildizfer F. et al. Association of fetuin A, adiponectin, interleukin 10 and total antioxidant capacity with IVF outcomes // Iran. J. Reprod. Med. 2014. V. 12. P. 747–754.

The authors declare that there are no conflicts of interest present.