PECULIARITIES OF IMMUNE REACTIVITY OF ENDOMETRIUM WITH NON-ATYPICAL HYPERPLASIA IN PATIENTS WITH INFERTILITY AND OBESITY

Authors

  • O. M. Nosenko Odessa National Medical University
  • S. V. Yurchenko Odessa National Medical University

DOI:

https://doi.org/10.11603/24116-4944.2020.2.11849

Keywords:

obesity, infertility, non-atypical endometrial hyperplasia, natural killer cells, immunohistochemistry, CD56 , CD16

Abstract

The aim of the study – to learn the features of the expression of NK cell subpopulations in the endometrium with non-atypical hyperplasia in patients with infertility and obesity.

Materials and Methods. The study included 84 infertile women with non-atypical endometrial hyperplasia (NAEH), including 44 with normal body weight and 40 with obesity, and 30 relatively healthy women in the control group. Endometrial samples were taken on the 22nd day of the menstrual cycle during the proposed implantation window in women with NAEH – with hysteroscopy, and in women of the control group – with pipel-biopsy. Immunohistochemical determination of CD16+- and CD56+ NK cells in the endometrium was carried out by the avidin-streptavidin-peroxidase method using the corresponding monoclonal antibodies.

Results and Discussion. In infertile women with NAEH, there was an excessive activation of immune reactivity in the endometrium with increased infiltration of its CD56+ and cytotoxic CD16+ NK cells: the expression of CD56 + was 8.14 times higher than the same control parameters ((56.91±2.43) versus (7.18±0.41) ‰, p<0.01), СD16+ – 48.04 times ((41.31±1.84) versus (0.88±0.15) ‰,
p<0.01). At the same time, the content of CD56 + NK cells in the endometrium of women with NAEH and obesity was 1.28 times lower than that in patients with normal body weight ((49.61±3.19) versus (63.55±3.34) ‰, p<0.01); CD16 + content – 1.32 times ((35.32±3.14) versus (46.75±1.71) ‰, p<0.01).

Conclusions. Obesity in infertile women with NHE due to systemic chronic inflammation leads to a decrease in the number and cytotoxicity of NK cells in the endometrium during the expected window of implantation compared to a similar pathology in persons with normal body weight, which may be a factor in the progression of the corresponding neoplastic changes.

Author Biographies

O. M. Nosenko, Odessa National Medical University

Doctor of Medical Sciences, Professor of the Department of Obstetrics and Gynecology of the Odessa National Medical University

S. V. Yurchenko, Odessa National Medical University

graduate student of the Department of Obstetrics and Gynecology of Odessa National Medical University

References

Boychuk, A.V., Shadrina, V.S., & Vereshchagina, T.V. (2019). Hiperplaziia endometriia – suchasnyi systemno-patohenetychnyi pohliad na problemu (ohliad literatury) [Endometrial hyperplasia is a modern systemic-pathogenetic view of the problem (literature review)]. Aktualni pytannia pediatrii, akusherstva ta hinekolohii – Current Issues of Pediatrics, Obstetrics and Gynecology, 1, 67-72. DOI:10.11603/24116-4944.2019.1.9906 [in Ukrainian].

Vovk, I.B., Borisyuk, O.Y., & Gorban, N.Ye. (2016). Sovremennye predstavleniya o giperplazii endometriya [Modern ideas about endometrial hyperplasia]. Medychna hazeta «Zdorovia Ukrainy». Hinekologiya. Akusherstvo. Reproduktolohiia – Medical newspaper "Health of Ukraine". Gynecology. Obstetrics. Reproductology, 2 (22), 70-73 [in Russian].

Yefimenko, O.O., & Deiniuk, C.D. (2018). Vplyv ozhyrinnia na rozvytok hiperplazii endometriia v zhinok riznoho viku [The effect of obesity on the development of endometrial hyperplasia in women of different ages]. Reproduktyvna endokrynolohiia – Reproductive Endocrinology, 4 (42), 28-33 [in Ukrainian].

Tatarchuk, T.F., Kalugina, L.V., & Tutchenko, T.N. (2015). Giperplasticheskie protsessyi endometriya: chto novogo? [Endometrial hyperplastic processes: what᾽s new?]. Reproduktivnaya endokrinologiya – Reproductive Endocrinology, 5 (25), 7-13 [in Russian].

World Health Organization. Obesity and overweight fact sheet 2016. Retrieved from: http://www.who.int/mediacentre/factsheets/fs311/en/.

Souter, I., Baltagi, L.M., Kuleta, D., Meeker, J.D., & Petrozza, J.C. (2011). Women, weight, and fertility: the effect of body mass index on the outcome of superovulation/intrauterine insemination cycles. Fertil. Steril., 95 (3), 1042-1047. DOI:10.1016/j.fertnstert.2010.11.062.

Horban, N.Ye., Vovk, I.B., Lysiana, T.O., Ponomariova, I.H., & Zhulkevych, I.V. (2019). Peculiarities of uterine ca­vity biocenosis in patients with different types of endometrial hyperproliferative pathology. Journal of Medicine and Life, 12 (3), 266-270.

Boots, C.E., Bernardi, L.A., & Stephenson, M.D. (2014). Frequency of euploid miscarriage is increased in obese women with recurrent early pregnancy loss. Fertil. Steril., 102 (2), 455-459. DOI:10.1016/j.fertnstert.2014.05.005.

Broughton, D.E., & Moley, K.H. (2017). Obesity and female infertility: potential mediators of obesity᾽s impact. Fertil. Steril., 107 (4), 840-847. DOI:10.1016/j.fertnstert.2017.01.017.

Fedorcsák, P., Dale, P.O., Storeng, R., Ertzeid, G., Bjercke, S., Oldereid, N., ..., & Tanbo, T. (2004). Impact of overweight and underweight on assisted reproduction treatment. Hum. Reprod. (Oxf., Engl.), 19 (11), 2523-2528. DOI:10.1093/humrep/deh485.

Berger, N.A. (2014). Obesity and cancer pathogenesis. Ann. N.-Y. Acad. Sci., 1311, 57-76. DOI:10.1111/nyas.12416.

Ackerman, S.E., Blackburn, O.A., Marchildon, F., & Cohen, P. (2017). Insights into the link between obesity and cancer. Curr. Obes. Rep., 6 (2), 195-203. DOI:10.1007/s13679-017-0263-x.

Himbert, C., Delphan, M., Scherer, D., Bowers, L.W., Hursting, S., & Ulrich, C.M. (2017). Signals from the adipose microenvironment and the obesity-cancer link-a systematic review. Cancer Prev. Res. (Phila), 10 (9), 494-506. DOI:10.1158/1940-6207.

Kosaraju, R., Guesdon, W., Crouch, M.J., Teague, H.L., Sullivan, E.M., Karlsson, E.A., ..., & Shaikh, S.R. (2017). B cell activity is impaired in human and mouse obesity and is responsive to an essential fatty acid upon murine influenza infection. J. Immunol. (Baltimore, Md.: 1950), 198 (12), 4738-4752. DOI:10.4049/jimmunol.1601031.

Gerriets, V.A., & MacIver, N.J. (2014). Role of T cells in malnutrition and obesity. Front. Immunol., 5, 379. DOI:10.3389/fimmu.2014.00379.

Żelechowska, P., Agier, J., Kozłowska, E., & Brzezińska-Błaszczyk, E. (2018). Mast cells participate in chronic low-grade inflammation within adipose tissue. Obes. Rev., 19 (5), 686-697. DOI:10.1111/obr.12670.

Mraz, M., & Haluzik, M. (2014). The role of adipose tissue immune cells in obesity and low-grade inflammation. J. Endocrinol., 222 (3), R113-R127. DOI:10.1530/JOE-14-0283.

Castoldi, A., Naffah de Souza, C., Câmara, N.O., & Moraes-Vieira, P.M. (2016). The macrophage switch in obesity development. Front. Immunol., 6, 637. DOI:10.3389/fimmu.2015.00637.

Bähr, I., Jahn, J., Zipprich, A., Pahlow, I., Spielmann, J.,

& Kielstein, H. (2018). Impaired natural killer cell subset phenotypes in human obesity. Immunol. Res., 66 (2), 234-244. DOI:10.1007/s12026-018-8989-4.

Bähr, I., Spielmann, J., Quandt, D., & Kielstein, H. (2020). Obesity-associated alterations of natural killer cells and immunosurveillance of cancer. Front. Immunol., 11, 245. DOI:10.3389/fimmu.2020.00245.

Poznanski, S.M., & Ashkar, A.A. (2019). What defines NK cell functional fate: Phenotype or metabolism? Front. Immunol., 10, 1414. DOI:10.3389/fimmu.2019.01414.

Sharp, H.T., & Adelman, M. (2017). Update on abnormal uterine bleeding. Endometrial sampling and obesity: Forget the "age 45" rule. OBG. Manag., 29 (4), 30-36.

Zhulkevych, I.V., & Kryvokulsky, B.D. (2018). Personalizatsiia v onkolohii: indyvidualnyi pidkhid do profilaktyky tromboembolichnykh uskladnen pry panhisterektomii [Personalization in oncology: individual approach to the prevention of thromboembolic complications during hysterectomy]. Visnyk sotsialnoi hihiieny ta orhanizatsii okhorony zdorovia Ukrainy – Bulletin of Social Hygiene and Health Care Organization of Ukraine, 4 (78), 11-18 [in Ukrainian].

Michelet, X., Dyck, L., Hogan, A., Loftus, R.M., Duquette, D., Wei, K., ..., & Lynch, L. (2018). Metabolic reprogramming of natural killer cells in obesity limits antitumor responses. Nat. Immunol., 19 (12), 1330-1340. DOI:10.1038/s41590-018-0251-7.

Published

2021-03-04

How to Cite

Nosenko, O. M., & Yurchenko, S. V. (2021). PECULIARITIES OF IMMUNE REACTIVITY OF ENDOMETRIUM WITH NON-ATYPICAL HYPERPLASIA IN PATIENTS WITH INFERTILITY AND OBESITY. Actual Problems of Pediatrics, Obstetrics and Gynecology, (2), 119–124. https://doi.org/10.11603/24116-4944.2020.2.11849

Issue

Section

OBSTETRICS AND GYNECOLOGY