Peculiarities of proteome profile of eutopic endometrium in women with adenomyosis depending on fertility

O. M. Nosenko, O. M. Kosyuga


In recent years, several studies have reported a correlation between adenomyosis and major obstetric adverse effects. Implantation failures can be caused by changes in the expression of some molecules, referred to as "implantation markers", which are expressed by the endometrium and are required for successful interaction between the embryo and endometrium. The purpose of the study was to determine the features of the proteomic profile of the endometrium in women with adenomyosis, depending on their fertility. Material and methods. A comparative immunohistochemical (IGC) analysis of 102 eutopic endometrial specimens from women of reproductive age with adenomyosis and infertility (group I) was performed; from 20 nonpregnant women with adenomyosis who had a history of desired pregnancy and ended in childbirth and did not record episodes of miscarriages (group II), as well as from 30 conditionally gynecologically healthy women who applied for the introduction of an intrauterine system for contraception (control group C). A biopsy of the eutopic endometrium was performed on P+6 day of the menstrual cycle, during the period of the expected implantation window, with the help of aspiration pipel-curette. In immunohistochemical (IGC) determination of the proteomic profile of the endometrium HOXA10 was stained with monoclonal antibodies (MAB) to HOXA10 (sc-17159, Santa Cruz Biotechnology, USA); LIF - murine MAB against LIF (J-14F: SC-80159, Santa Cruz Biotechnology Inc., USA); sgp130 - goat polyclonal antibodies (PAB) anti-gp130 (BAF 228, supplied 50 μg / ml, R&D Systems); IL-6 - primary rabbit antibodies (code No CXH1-066LS, supplied as rabbit IgG 20 µg / ml; Cambridge Bioscience, UK). Results. It was found that important factors of reproductive disorders in women with adenomyosis are: changes in the proteomic profile of the eutopic endometrium on the day of the expected implant window, such as a decrease in HOXA 10 expression in the stroma by 1.52 (p<0.01) and in the glands by 1.46 times (p<0.01), LIF in glands - in 1.12 (p<0.01) and sgp130 - in 2.52 (p<0.01), as well as increased secretion in glands of IL-6 in 1,99 (p<0.01) times. In fertile women with adenomyosis, less pronounced changes in the proteomic profile of the eutopic endometrium are observed, which creates the conditions for successful realization of reproductive intentions, including a decrease in expression of HOXA 10 in the stroma by 1.48 times (p<0.01), in the glands - in 1.12 (p>0.05); secretion in glands of LIF - in 1.06 (p>0.05) and gp130 - in 1.98 (p<0.01); increased IL-6 1.08 times (p<0.05). Conclusions. Changes in the proteomic profile of the endometrium play an important role in the occurrence of reproductive disorders in adenomyosis.


adenomyosis; endometrium; infertility; proteomic profile; HOXA10; Leukemia inhibitory factor; glycoprotein 130; interleukin-6

Full Text:



Berlac JF, Hartwell D, Skovlund CW, Langhoff-Roos J, Lidegaard O. Endometriosis increases the risk of obstetrical and neonatal complications. Acta Obstet Gynecol Scand. 2017;96(6):751-760. doi: 10.1111/aogs.13111.

Conti N, Cevenini G, Vannuccini S, Orlandini C, Valensise H, Gervasi MT, et al. Women with endometriosis at first pregnancy have an increased risk of adverse obstetric outcome. J Matern Fetal Neonatal Med. 2015;28(15):1795-8. doi: 10.3109/14767058.2014.968843.

Di Donato N, Montanari G, Benfenati A, Leonardi D, Bertoldo V, Monti G, et al. Prevalence of adenomyosis in women undergoing surgery for endometriosis. Eur J Obstet Gynecol Reprod Biol. 2014; 181: 289-293. doi: 10.1016/j.ejogrb.2014.08.016.

Exacoustos C, Lauriola I, Lazzeri L, De Felice G, Zupi E. Complications during pregnancy and delivery in women with untreated rectovaginal deep infiltrating endometriosis. Fertil Steril. 2016; 106: 1129-1135. e1. doi: 10.1016/j.fertnstert.2016.06.024.

Fischer CP, Kayisili U, Taylor HS. HOXA10 expression is decreased in endometrium of women with adenomyosis. Fertil Steril. 2011 Mar 1;95(3):1133-6. doi: 10.1016/j.fertnstert.2010.09.060.

Gladchuk IZ, Rozhkovskaya NN, Garbuzenko ND, Stamova NA. Age characteristics of uterine motility in infertile women with adenomyosis, uterine fibroids and their combination. The health of woman. 2016;3(109):149–152.

Glavind MT, Forman A, Arendt LH, Nielsen K, Henriksen TB. Endometriosis and pregnancy complications: a Danish cohort study. Fertil Steril. 2017;107(1):160-166. doi: 10.1016/j.fertnstert.2016.09.020.

Harada T, Taniguchi F, Onishi K, Kurozawa Y, Hayashi K, Harada T, et al. Obstetrical complications in women with endometriosis: a cohort study in Japan. PLoS One. 2016; 11(12):e0168476. doi: 10.1371/journal.pone.0168476.

Hashimoto A, Iriyama T, Sayama S, Nakayama T, Komatsu A, Miyauchi A, et al. Adenomyosis and adverse perinatal outcomes: increased risk of second trimester miscarriage, preeclampsia, and placental malposition. J Matern Fetal Neonatal Med. 2018;31(3):364-369. doi: 10.1080/14767058.2017.1285895.

Kaminsky BB, Prokopovich EV. An alternative to hormonal and non-steroidal anti-inflammatory drugs in the treatment of secondary dysmenorrhea caused by adenomyosis. The health of woman. 2018; 4: 66-70.

Kutsenko II, Kravtsova EI, Simovonik AN, Rudeeva OA. Ultrasound diagnosis of adenomyosis I degree of spread. Modern problems of science and education. 2017: 6. URL: view? Id = 27350.

Mannini L, Sorbi F, Noci I, Ghizzoni V, Perelli F, Di Tommaso M, et al. New adverse obstetrics outcomes associated with endometriosis: a retrospective cohort study. Arch Gynecol Obstet. 2017; 295: 141-151.

Mikolajczyk M, Wirstlein P, Skrzypczak J. Leukaemia inhibitory factor and interleukin-11 levels in uterine flushings of infertile patients with endometriosis. Hum Reprod. 2006 Dec;21(12):3054-8.

Pitman H, Innes BA, Robson SC, Bulmer JN, Lash GE. Altered expression of interleukin-6, interleukin-8 and their receptors in decidua of women with sporadic miscarriage. Hum Reprod. 2013;28(8):2075-86. doi: 10.1093/humrep/det233.

Vdovichenko JuP, Gnip IP, Vorobiy VD. Optimization of diagnostics and endoscopic treatment of adenomyosis and disorders of reproductive function. Woman's health. 2015; 6:149–151.

Winship A, Correia J, Zhang JG Nicola NA, Dimitriadis E. Leukemia Inhibitory Factor (LIF) Inhibition during Mid-Gestation Impairs Trophoblast Invasion and Spiral Artery Remodeling during Pregnancy in Mice. PLoS One. 2015;10(10):e0129110. doi: 10.1371/journal.pone.0129110.

Xu B, Geerts D, Bu Z, Ai J, Jin L, Li Y, et al. Regulation of endometrial receptivity by the highly expressed HOXA9, HOXA11 and HOXA10 HOX-class homeobox genes. Hum Reprod. 2014;29(4):781-90. doi: 10.1093/humrep/deu004.

Yen CF, Liao SK, Huang SJ, Tabak S, Arcuri F, Lee CL, et al. Decreased Endometrial Expression of Leukemia Inhibitory Factor Receptor Disrupts the STAT3 Signaling in Adenomyosis During the Implantation Window. Reprod Sci. 2017;24(8):1176-1186. doi: 10.1177/1933719116681515.



  • There are currently no refbacks.

Copyright (c) 2019 © The Author (s) 2019

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Journal of Education, Health and Sport formerly Journal of Health Sciences

Declaration on the original version.

Editors indicates that the main version of the magazine is to issue a "electronic".

The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019.

1223 Journal of Education, Health and Sport eISSN 2391-8306 7

ISSN 2391-8306 formerly ISSN: 1429-9623 / 2300-665X

Archives 2011 - 2014

PBN 2011 - 2014

POL-index 2011 - 2014

BASE 2011 - 2014

Indexed in Bases, Bazy indeksacyjne: ERIH Plus, Worldcat, PBN/POL-Index, ICI Journals Master List, Directory of Open Access Journals (DOAJ), ZBD, Ulrich's periodicals, Google Scholar, Polska Bibliografia Lekarska

US NLM = 101679844

101679844 - NLM Catalog Result - NCBI

Find a library that holds this journal:

Journal Language(s): English 

PBN Poland



Redaction, Publisher and Editorial Office

Instytut Kultury Fizycznej Uniwersytet Kazimierza Wielkiego w Bydgoszczy, Institute of Physical Education Kazimierz Wielki University in Bydgoszcz, Poland 85-091 Bydgoszcz ul. Sportowa 2 Copyright by Instytut Kultury Fizycznej UKW w Bydgoszczy  Open Access ISSN 2391-8306 formerly ISSN: 1429-9623 / 2300-665X

The journal has been approved for inclusion in ERIH PLUS.

The ERIH PLUS listing of the journal is available at

SIC Science citation index (calculated on the basis of TCI and Page Rank) 0

Russian Impact factor 0.16

Indexed in Index Copernicus Journals Master List.,p24782242,3.html

ICV 2018 = 95.95 ICV 2017 = 91.30 ICV 2016 = 84.69 ICV 2015 = 93.34 ICV 2014 = 89.51 Standardized Value: 8.27 ICV 2013: 7.32 ICV 2012: 6.41 ICV 20115.48

The InfoBase Index IBI Factor for the year 2015 is 3.56 in InfoBase


Universal Impact Factor 1.78 for year 2012. (

Indexed in Polish Scholarly Bibliography (PBN) (PBN Polska Bibliografia Naukowa) (

is a portal of the Polish Ministry of Science and Higher Education, collecting information on publications of Polish scientists and on Polish and foreign scholarly journals. Polish Scholarly Bibliograhpy is a part of POL-on - System of Information on Higher Education. It is operated by the Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw.

Indexed in Russian Sciences Index Российский индекс научного цитирования (РИНЦ)

Indexed in Arianta Polish scientific and professional electronic journals Aneta Drabek i Arkadiusz Pulikowski