Prognostic ability of seminal plasma lipidomic analysis in predicting the success of microTESE in men with azoospermia


Cite item

Full Text

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

Abstract

Introduction: The aim of this work is to assess the possibility of metabolomic (specifically lipidomic) analysis of seminal plasma to identify patients with preserved focal spermatogenesis in the testes who may have a reasonable chance of sperm retrieval during the microTESE procedure. Materials and methods: lipid composition of semen plasma samples from 64 men with azoospermia and 24 fertile control men was analyzed. Lipids were isolated from semen by a modified Folch extraction method. Lipid extracts were analyzed by reverse phase liquid chromatography coupled to mass spectrometry. Lipidomic data were compared with the results of the microTESE procedure. Results: Comparison of two groups revealed a statistically significant difference in concentration for 23 lipids detected in positive ion mode and 37 lipids detected in negative ion mode. Those lipids mainly belong to hexosylceramides, sphingomyelins and phosphatidylcholines, phosphatidylethanolamines and their ethers. In multivariate analysis content of SM d16: 1/18:0 lipid (beta coefficient: -7.23; 95% confidence interval [95% CI]: -11.93 to - 2.53; odds ratio: 7.23e-04; CI for odds ratio: 6.59e-06 to 7.93e-02; Wald’s test: -3.02; p=0.003), content of TG 14: 1_16 : 0_18: 3 lipid (beta 2.95; 95% CI 0.98 to 4.93; odds ratio: 1.92e + 01; CI for odds ratio: 2.66e + 00 to 1.39e + 02 ; Wald’s test: 2.93; p=0.003) and testicular volume (beta: 0.14; 95% CI: 0.04 to 2.45; odds ratio: 1.15e + 00; CI odds ratio: from 1.04e + 00 to 1.27e + 00; Wald’s test: 2.65; p=0.008) were significantly associated with positive MicroTESE outcome. The sensitivity of this regression model was 61%, the specificity was 83%, and the AUC was 0.75. Conclusions: seminal plasma serves as a rich source of biological markers for identifying patients with preserved focal spermatogenesis in the testes. Seminal plasma lipidomic profile of the of patients in the control group with normal spermatogenesis clearly differs from the profile of patients with azoospermia, also there was a significant difference in content of a difference in lipids between patients with positive and negative microTESE outcomes. These are preliminary results and further research is needed to confirm the validity of the resulting lipid panel.

Full Text

Restricted Access

About the authors

S. I Gamidov

Acad. V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia

Email: safargamidov@yandex.ru
doctor of medical science, chief urologist of Kulakov Center, professor of obstetrics, gynecology and perinatology department of Sechenov University

T. V Shatylko

Acad. V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: dialectic.law@gmail.com
candidate of medical science, urologist of andrology and urology department

A. Kh Tambiev

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

Email: dr.tambiev@gmail.com
postgraduate student at the Department Obstetrics, Gynecology, Perinatology and Reproductology, Institute of Professional Education

A. O Tokareva

Acad. V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: alisa.tokareva@phystech.edu
researcher of proteomics and metabolomics laboratory in human reproduction

V. V Chagovets

Acad. V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: vvchagovets@gmail.com
candidate of physical and mathematical sciences, senior researcher of proteomics and metabolomics laboratory in human reproduction

T. B Bitsoev

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

Email: 6646362@mail.ru
postgraduate student at the Department Obstetrics, Gynecology, Perinatology and Reproductology, Institute of Professional Education

N. L Starodubtseva

Acad. V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: n_starodubtseva@oparina4.com
candidate of biological science, chief of proteomics and metabolomics laboratory in human reproduction

A. Yu. Popova

Acad. V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: alina-dock@yandex.ru
candidate of medical science, urologist of andrology and urology department

V. E Frankevich

Acad. V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: v_frankevich@oparina4.ru
candidate of physical and technical science, chief of department of systemic biology in reproduction

References

  1. Гамидов С.И., Попова А.Ю., Гасанов Н.Г., Овчинников Р.И., Наумов Н.П., Шатылко Т.В. Роль методов хирургического получения сперматозоидов у пациентов с азооспермией в программах вспомогательных репродуктивных технологий (обзор литературы). Андрология и генитальная хирургия. 2018; 19(3) :27-34. https://doi.org/10.17650/2070-9781-2018-19-3-27-34
  2. Goodacre R., Vaidyanathan S., Dunn W.B., Harrigan G.G., Kell D.B. Metabolomics by numbers: acquiring and understanding global metabolite data. Trends Biotechnol. 2004;22:245-252.
  3. Downes A., Elfick A. Raman spectroscopy and related techniques in biomedicine. Sensors. 2010; 10:1871-1889.
  4. Kovac J.R., Lipshultz L.I. The significance of insulin-like factor 3 as a marker of intratesticular testosterone. Fertil Steril. 2013; 99:66-67.
  5. Kell D.B. Metabolomics and systems biology: making sense of the soup. Curr Opin Microbiol. 2004;7:296-307.
  6. Shatylko T.V., Gamidov S.I., Frankevich V.E., Starodubtseva N.L., Gasanov N.G., Tambiev A.H. Asthenozoospermia and proteomic factors of regulation of sperm motility. Obstetrics and gynecology. 2020;4:37-45
  7. Шатылко Т.В., Гамидов С.И., Франкевич В.Е., Стародубцева Н.Л., Гасанов Н.Г., Тамбиев А.Х. Астенозооспермия и протеомные факторы регуляции подвижности сперматозоидов. Акушерство и гинекология. 2020;4:37-44. https://dx.doi.org/10.18565/aig.2020.4.37-44
  8. Гамидов С.И., Шатылко Т.В., Тамбиев А.Х., Гасанов Н.Г., Попова А.Ю. Альравашдех А.А.А. Трудности в дифференциальной диагностике обструктивной и необструктивной азооспермии. Вестник урологии. 2022;2:19-31. doi: 10.21886/2308-6424-2022-10 2-19-31.
  9. Гамидов С.И., Шатылко Т.В., Тамбиев А.Х., Токарева А.О., Чаговец В.В., Бицоев Т.Б., Стародубцева Н.Л., Попова А.Ю., Франкевич В.Е. Липидомный профиль семенной плазмы при необструктивной азооспермии с остановкой созревания сперматозоидов. Вестник урологии. 2021 ;9(4):30-39. doi: 10.21886/2308-64242021-9-4-30-39.
  10. Бржозовский А.Г., Стародубцева Н.Л., Бугрова А.Е., Кононихин А.С., Чаговец В.В., Шатылко Т.В., Гамидов С.И., Тамбиев А.Х., Попова А.Ю., Гасанов Н.Г., Бицоев Т.Б., Франкевич В.Е. Прогностические возможности протеомного анализа семенной плазмы у мужчин с азооспермией. Андрология и генитальная хирургия. 2021 ;22(3): 18-24. https://doi.org/10.17650/1726-9784-2021-22-3-18-24
  11. Lamb D. A look towards the future: advances in andrology expected to revolutionize the diagnosis and treatment of the infertile male. In: Infertility in the Male. Cambridge University Press. 2009; p. 642-653.
  12. Kovac J.R., Pastuszak A.W., Lamb D.J. The use of genomics, proteomics, and metabolomics in identifying biomarkers of male infertility. Fertil Steril. 2013; 99:998-1007.
  13. Oliver S.G., Winson M.K., Kell D.B., Baganz F. Systematic functional analysis of the yeast genome. Trends Biotechnol. 1998; 16:373-378.
  14. Shulaev V. Metabolomics technology and bioinformatics. Brief Bioinform. 2006; 7:128-139
  15. Fiehn O. Metabolomics-the link between genotypes and phenotypes. Plant Mol Biol. 2002; 48:155-171.
  16. Denkert C., Budczies J., Kind T., Weichert W., Tablack P., Sehouli J., Niesporek S., Konsgen D., Dietel M., Fiehn O. Mass spectrometry-based metabolic profiling reveals different metabolite patterns in invasive ovarian carcinomas and ovarian borderline tumors. Cancer Res. 2006; 66:10795-10804.
  17. Qi Y., Song Y., Gu H., Fan G., Chai Y. Global metabolic profiling using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. In: Mass Spectrometry in Metabolomics. Springer, N.-Y. 2014; pp 15-27.
  18. Fernie A.R., Trethewey R.N., Krotzky A.J., Willmitzer L. Metabolite profiling: from diagnostics to systems biology. Nat Rev Mol Cell Biol. 2004; 5:763-769.
  19. Wood P.L., Scoggin K., Ball B.A., Troedsson M.H., Squires E.L. Lipidomics of equine sperm and seminal plasma: Identification of amphiphilic (O-acyl)-m-hydroxy-fatty acids. Theriogenology. 2016; 86:1212-1221.
  20. Chagovets V., Wang Z., Kononikhin A., Starodubtseva N., Borisova A., Salimova D., et al. A Comparison of Tissue Spray and Lipid Extract Direct Injection Electrospray Ionization Mass Spectrometry for the Differentiation of Eutopic and Ectopic Endometrial Tissues. J. Am Soc Mass Spectrom. 2017;6-8.
  21. Koelmel J., Kroeger N. et al. LipidMatch: an automated workflow for rule-based lipid identification using untargeted high-resolution tandem mass spectrometry data. BMC Bioinformatics, 2017.
  22. 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.
  23. Team, R.C. R: A language and environment for statistical computing. R. Foundation for Statistical Computing, Vienna, Austria. Available online: https://www.r-project.org
  24. Team, Rs. RStudio: Integrated Development for R. Available online: http://www.rstudio.com
  25. Gulaya N.M., Margitich V.M., Govseeva N.M., Klimashevsky V.M., Gorpynchenko I.I., Boyko M.I. Phospholipid composition of human sperm and seminal plasma in relation to sperm fertility. Arch Androl. 2001; May-Jun; 46(3):169-175.
  26. Arienti G., Carlini E., Polci A., Cosmi E.V., Palmerini C.A. Fatty acid pattern of human prostasome lipid. Arch Biochem Biophys. 1998;358(2):391- 395. doi: 10.1006/abbi.1998.0876. PMID: 9784255.

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