COMPARATIVE ANALYSIS OF THE LIPID COMPOSITION OF PERITONEAL FLUID AND BLOOD PLASMA IN PATIENTS WITH EXTERNAL GENITAL ENDOMETRIOSIS AND UTERINE MYOMA


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Objective. To enhance the efficiency of diagnosing external genital endometriosis by direct mass spectrometry. Subjects and methods. A case-control study covered 100 patients with external genital endometriosis (a study group) and 50 patients with uterine myoma (a control group) who had been operated on at the Gynecology Department, V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation. The diagnosis of external genital endometriosis was based on diagnostic and therapeutic laparoscopy and finally confirmed histologically. To determine the lipid composition of blood and peritoneal fluid, their samples were obtained from all the study participants. The lipidome was qualitatively and quantitatively assessed using electrospray mass spectrometry. An analysis revealed more than 140 molecular characteristics, most of which were five lipid classes: phosphatidylcholines, phosphatidylethanolamines, sphingomyelins, diglycerides, and triglycerides. The obtained experimental data were analyzed using the multivariate partial lest squares-discriminant analysis (PLS-DA). The created statistical models well group data based on a case-control sign and could identify lipids, which make the greatest contribution to the clustering of the data. Results. Unlike the comparison group, the patients with endometriosis showed a substantial decrease in the blood and peritoneal fluid level of four lipids: phosphatidylcholine PC 36:4, lysophosphatidylcholine LPC 16:0, sphingomyelin SM 34:1, and phosphoethanolamine PE O-34:1. The level of phosphoethanolamine PE 0-20:0 was increased not only in the endometrial tissues, but also in the biological fluids of patients with endometriosis, suggesting the possible diagnostic value of this lipid. The sensitivity and specificity of the method was 93% and 95%, respectively for blood plasma; those were 90 and 95% for peritoneal fluid. Conclusion. This investigation confirms the involvement of phospholipids and sphingolipids in the pathophysiology of endometriosis and opens up new possibilities for the noninvasive diagnosis of external genital endometriosis.

Full Text

Restricted Access

About the authors

Anna Valerevna Borisova

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: aneta_b@mail.ru
PhD student Moscow 117997, Ac. Oparina str. 4, Russia

Vitaliy Viktorovich Chagovets

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: vvchagovets@gmail.com
PhD, Senior Researcher of Proteomics of Human Reproduction Moscow 117997, Ac. Oparina str. 4, Russia

Andrey Vladimirovich Kozachenko

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: andreykozachenko@list.ru
MD, PhD, Senior Researcher Moscow 117997, Ac. Oparina str. 4, Russia

Nataliia Leonidovna Starodubtseva

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia; Moscow Institute of Physics and Technology (State University)

Email: n_starodubtseva@oparina4.ru
PhD, Head of Laboratory of Proteomics of Human Reproduction Moscow 117997, Ac. Oparina str. 4, Russia; Dolgoprudnyi, Moscow Region

Alexey Sergeevich Kononikhin

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia; Moscow Institute of Physics and Technology (State University)

Email: a_kononihin@oparina4.ru
PhD, Researcher of Proteomics of Human Reproduction Moscow 117997, Ac. Oparina str. 4, Russia; Dolgoprudnyi, Moscow Region

Dinara Failevna Salimova

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia

Email: Salimova.1993@mail.ru
Student Moscow 119991, Malaya Pirogovskaya str. 8/21, Russia

Eugenia Aleksandrovna Kogan

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia

Email: koganevg@gmail.com
MD, PhD, professor, Head of the Department of Pathological Anatomy of the medical faculty Moscow 119991, Malaya Pirogovskaya str. 8/21, Russia

Leila Vladimirovna Adamyan

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: adamyanleila@gmail.com
Academician of the Russian Academy of Sciences, Professor, Honoured Scientist of the Russian Federation, Deputy Director for Scientific Affairs Moscow 117997, Ac. Oparina str. 4, Russia

Vladimir Evgenievich Frankevich

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: v_frankevich@oparina4.ru
PhD, Head of Department of Systems Biology in Reproduction Moscow 117997, Ac. Oparina str. 4, Russia

G. T SUKHIKH

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Moscow 117997, Ac. Oparina str. 4, Russia

References

  1. Адамян Л.В., Андреева Е.Н., Аполихина И.А., Беженарь В.Ф., Геворкян М.А., Гус А.И., Демидов В.Н., Калинина Е.А., Леваков С.А., Марченко Л.А., Попов А.А., Сонова М.М., Хашукова А.З., Чернуха Г.Е., Яроцкая Е.Л. Эндометриоз: диагностика, лечение, реабилитация. Федеральные клинические рекомендации по ведению больных. М.; 2013: 2-9
  2. Щеголев А.И., Быков А.Г., Туманова У.Н., Павлович С.В. Эндометриоз и развитие опухолей. Акушерство и гинекология. 2016; 11: 49-56. http://dx.doi.org/10.18565/aig.2016.11.49-56
  3. Фархат К.Н., Адамян Л.В. Аномалии развития матки и влагалища в сочетании с эндометриозом: тактика ведения и хирургическая коррекция. Акушерство и гинекология. 2016; 5: 96-102. http://dx.doi. org/10.18565/aig.2016.5.96-102
  4. Burney R.O., Giudice L.C. Pathogenesis and pathophysiology of endometriosis. Fertil. Steril. 2012; 98(3): 511-9.
  5. Бурлев В.А., Павлович С.В., Ильясова Н.А. Апоптоз и пролиферативная активность в эндометрии при перитонеальном эндометриозе. Бюллетень экспериментальной биологии и медицины. 2006; 141(2): 165-8.
  6. Мельников М.В., Чупрынин В.Д., Аскольская С.В., Хабас Г.Н., Матроницкий Р.Б., Вередченко А.В., Бурыкина П.Н., Попов Ю.В., Хачатрян А.М., Хачатрян А.М., Хилькевич Е.Г. Диагностика и тактика хирургического лечения инфильтративного эндометриоза у пациенток репродуктивного возраста. Акушерство и гинекология. 2012; 7: 42-9.
  7. Johnson N.P, Hummelshoj L. World Endometriosis Society Montpellier Consortium. Consensus on current management of endometriosis. Hum. Reprod. 2013; 28(6): 1552-68.
  8. Борисова А.В., Стародубцева Н.Л., Козаченко А.В., Чаговец В.В., Салимова Д.Ф., Кононихин А.С., Коган Е.А., Адамян Л.В., Франкевич В.Е., Сухих Г.Т. Исследование очагов эндометриоза различной локализации методом прямой масс-спектрометрии. Акушерство и гинекология. 2016; 9: 101-8. http://dx.doi.org/10.18565/aig.2016.9.101-8
  9. Vouk K., Hevir N., Ribic-Pucelj M., Haarpaintner G., Scherb H., Osredkar J. et al. Discovery of phosphatidylcholines and sphingomyelins as biomarkers for ovarian endometriosis. Hum. Reprod. 2012; 27(10): 2955-65.
  10. Dutta M., Joshi M., Srivastava S., Lodh I., Chakravarty B., Chaudhury K. A metabonomics approach as a means for identification of potential biomarkers for early diagnosis of endometriosis. Mol. Biosyst. 2012: 8(12): 3281-7.
  11. Lee Y.H., Tan C.W., Venkatratnam A., Tan C.S., Cui L., Loh S.F. et al. Dysregulated sphingolipid metabolism in endometriosis. J. Clin. Endocrinol. Metab. 2014; 99(10): 1913-21.
  12. Folch J., Lees M., Sloane Stanley G.H. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 1957; 226(1): 497-509.
  13. Trygg J., Wold S. Orthogonal projections to latent structures (O-PLS). J. Chemometrics. 2002; 16(3): 119-28.
  14. Sud M., Fahy E., Cotter D., Brown A., Dennis E.A., Glass C.K. et al. LMSD: LIPID MAPS structure database. Nucleic Acid Res. 2007; 35(Database issue): D527-32.
  15. Vouk K., Ribic-Pucelj M., Adamski J., Rizner T.L. Altered levels of acylcarnitines, phosphatidylcholines, and sphingomyelins in peritoneal fluid from ovarian endometriosis patients. J. Steroid Biochem. Mol. Biol. 2016; 159: 60-9.
  16. Дубинская Е.Д., Федорова Т.А., Лаптева Н.В., Великян О.М. Оксидативный стресс и эндогенная интоксикация у пациенток с бесплодием и перитонеальной формой эндометриоза с учетом полиморфизма гена NAT2. Проблемы репродукции. 2014; 4: 39-44.
  17. Лисица А.В., Пономаренко Е.А., Лохов П.Г., Арчаков А.И. Постгеномная медицина: альтернатива биомаркерам. Вестник Российской академии медицинских наук. 2016; 3: 255-60.
  18. Угаров Г.С. О роли воды и липидов в организации живой материи. Международный журнал прикладных и фундаментальных исследований. 2015; 5: 443-7.
  19. Pavlovic Z., Bakovic M. Regulation of phosphatidylethanolamine homeostasis - The critical role of CTP: phosphoethanolamine cytidylyltransferase (Pcyt2). Int. J. Mol. Sci. 2013; 14(2): 2529-50.
  20. Zhu L., Bakovic M. Breast cancer cells adapt to metabolic stress by increasing ethanolamine phospholipid synthesis and CTP: ethanolaminephosphate cytidylyltransferase-Pcyt2 activity. Biochem. Cell Biol. 2012; 90(2): 188-99.
  21. Gibellini F., Smith T.K. The Kennedy pathway - de novo synthesis of phosphatidylethanolamine and phosphatidylcholine. IUBMB Life. 2010; 62(6): 414-28.
  22. Bleijerveld O.B., Klein W., Vaandrager A.B., Helms J.B., Houweling M. Control of the CDPethanolamine pathway in mammalian cells: Effect of ctp:phosphoethanolamine cytidylyltransferase overexpression and the amount of intracellular diacylglycerol. Biochem. J. 2004; 379(Pt 3): 711-9.
  23. Zhu L., Johnson C., Bakovic M. Stimulation of the human CTP: phosphoethanolamine cytidylyltransferase gene by early growth response protein 1. J. Lipid Res. 2008; 49(10): 2197-211.
  24. Bhoumik A., Fichtman B., Derossi C., Breitwieser W., Kluger H.M., Davis S. et al. Suppressor role of activating transcription factor 2 (ATF2) in skin cancer. Proc. Natl. Acad. Sci. USA. 2008; 105(5): 1674-9.
  25. Burney R.O., Giudice L.C. Pathogenesis and pathophysiology of endometriosis. Fertil. Steril. 2012; 98(3): 511-9.
  26. Burney R.O., Talbi S., Hamilton A.E., Vo K.C., Nyegaard M., Nezhat C.R. et al. Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis, Endocrinology. 2007; 148(8): 3814-26.
  27. Corre I., Niaudet C., Paris F. Plasma membrane signaling induced by ionizing radiation. Mutat. Res. 2010; 704(1-3): 61-7.
  28. Santulli P., Marcellin L., Noel J.C., Borghese B., Fayt I., Vaiman D. et al. Sphingosine pathway deregulation in endometriotic tissues. Fertil. Steril. 2012; 97(4): 904-11.
  29. Santanam N., Fahrmann J., Cook C., King H., Egleton R., Dawley B.L. Oxidized lipoproteins are the alleged pain molecules in the peritoneal fluid of women with endometriosis. Fertil. Steril. 2010; 94(4, Suppl.): S145.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies