open access

Vol 91, No 5 (2020)
Research paper
Published online: 2020-05-29
Get Citation

The correlation between unexplained infertility and exosomes

Yıldız Uyar1, Melike Özgül1, Sevtap Gökap1, Gülay Ok1, Ayça Tan1, Hafize Seda Vatansever1
DOI: 10.5603/GP.2020.0048
·
Pubmed: 32495928
·
Ginekol Pol 2020;91(5):240-246.
Affiliations
  1. Manisa Celal Bayar University Medical Faculty, Manisa, Turkey

open access

Vol 91, No 5 (2020)
ORIGINAL PAPERS Gynecology
Published online: 2020-05-29

Abstract

Objectives: Endometrial receptivity plays the most important role for successful implantation. Increasing endometrial
receptivity may improve infertility and increase Assisted Reproductive Technologies success. The aim of this study was to
investigate the effect of exosome specific markers CD63 and CD9 which are promising molecules in the pathogenesis and
treatment of many diseases on endometrial receptivity in women with unexplained infertility.
Material and methods: This prospective study was conducted between November 2015 and March 2017. Proliferation
and secretion periods of endometrial samples from fertile and infertile cases were collected. The paraffin-embedded
tissue sections were stained with hematoxylin-eosin for the immunohistochemical analysis distributions of CD63 and CD9.
Results: The results of this study demonstrated that the CD63 immunoreactivity was higher in both luminal and glandular
epithelium of infertile patients when compared with fertile patients during the proliferative phase (p = 0.009, p = 0.008). In
the infertile proliferation phase, endometrium CD9 immunoreactivity was rarely detected in both the luminal and glandular
epithelium. In the secretion phase of endometrium, CD9 immunoreactivity was mild in fertile patients, the increased
immunoreactivity of CD9 was observed in both luminal and glandular epithelium of infertile patients (p = 0.037, p = 0.037).
Conclusions: Increased levels of CD63 in infertile proliferation phase endometrium should represent an unfavorable
signaling. Moreover, the increased levels of CD9 in infertile secretion phase endometrium could be used as a biomarker
to evaluate endometrial receptivity. These exosome-specific markers can be considered as potential molecular markers
of infertility.

Abstract

Objectives: Endometrial receptivity plays the most important role for successful implantation. Increasing endometrial
receptivity may improve infertility and increase Assisted Reproductive Technologies success. The aim of this study was to
investigate the effect of exosome specific markers CD63 and CD9 which are promising molecules in the pathogenesis and
treatment of many diseases on endometrial receptivity in women with unexplained infertility.
Material and methods: This prospective study was conducted between November 2015 and March 2017. Proliferation
and secretion periods of endometrial samples from fertile and infertile cases were collected. The paraffin-embedded
tissue sections were stained with hematoxylin-eosin for the immunohistochemical analysis distributions of CD63 and CD9.
Results: The results of this study demonstrated that the CD63 immunoreactivity was higher in both luminal and glandular
epithelium of infertile patients when compared with fertile patients during the proliferative phase (p = 0.009, p = 0.008). In
the infertile proliferation phase, endometrium CD9 immunoreactivity was rarely detected in both the luminal and glandular
epithelium. In the secretion phase of endometrium, CD9 immunoreactivity was mild in fertile patients, the increased
immunoreactivity of CD9 was observed in both luminal and glandular epithelium of infertile patients (p = 0.037, p = 0.037).
Conclusions: Increased levels of CD63 in infertile proliferation phase endometrium should represent an unfavorable
signaling. Moreover, the increased levels of CD9 in infertile secretion phase endometrium could be used as a biomarker
to evaluate endometrial receptivity. These exosome-specific markers can be considered as potential molecular markers
of infertility.

Get Citation

Keywords

exosomes, endometrium, fertility, infertility, embryo implantation

About this article
Title

The correlation between unexplained infertility and exosomes

Journal

Ginekologia Polska

Issue

Vol 91, No 5 (2020)

Article type

Research paper

Pages

240-246

Published online

2020-05-29

DOI

10.5603/GP.2020.0048

Pubmed

32495928

Bibliographic record

Ginekol Pol 2020;91(5):240-246.

Keywords

exosomes
endometrium
fertility
infertility
embryo implantation

Authors

Yıldız Uyar
Melike Özgül
Sevtap Gökap
Gülay Ok
Ayça Tan
Hafize Seda Vatansever

References (30)
  1. Kumar N, Singh AK. Trends of male factor infertility, an important cause of infertility: A review of literature. J Hum Reprod Sci. 2015; 8(4): 191–196.
  2. Zegers-Hochschild F, Adamson GD, de Mouzon J, et al. International Committee for Monitoring Assisted Reproductive Technology, World Health Organization, International Committee for Monitoring Assisted Reproductive Technology, World Health Organization. The International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) Revised Glossary on ART Terminology, 2009. Hum Reprod. 2009; 24(11): 2683–2687.
  3. Zegers-Hochschild F, Adamson GD, Dyer S, et al. The International Glossary on Infertility and Fertility Care, 2017. Fertil Steril. 2017; 108(3): 393–406.
  4. Cakmak H, Taylor HS, Cakmak H, et al. Molecular mechanisms of treatment resistance in endometriosis: the role of progesterone-hox gene interactions. Semin Reprod Med. 2010; 28(1): 69–74.
  5. Salamonsen LA, Edgell T, Rombauts LJF, et al. Proteomics of the human endometrium and uterine fluid: a pathway to biomarker discovery. Fertil Steril. 2013; 99(4): 1086–1092.
  6. Sharkey AM, Smith SK. The endometrium as a cause of implantation failure. Best Pract Res Clin Obstet Gynaecol. 2003; 17(2): 289–307.
  7. Ozkan ZS, Deveci D, Kumbak B, et al. What is the impact of Th1/Th2 ratio, SOCS3, IL17, and IL35 levels in unexplained infertility? J Reprod Immunol. 2014; 103: 53–58.
  8. Dear JW, Street JM, Bailey MA. Urinary exosomes: a reservoir for biomarker discovery and potential mediators of intrarenal signalling. Proteomics. 2013; 13(10-11): 1572–1580.
  9. Stahl PD, Raposo G. Extracellular Vesicles: Exosomes and Microvesicles, Integrators of Homeostasis. Physiology (Bethesda). 2019; 34(3): 169–177.
  10. Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013; 200(4): 373–383.
  11. Abels ER, Breakefield XO. Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake. Cell Mol Neurobiol. 2016; 36(3): 301–312.
  12. Rosenbluth EM, Shelton DN, Wells LM, et al. Human embryos secrete microRNAs into culture media--a potential biomarker for implantation. Fertil Steril. 2014; 101(5): 1493–1500.
  13. Tannetta D, Dragovic R, Alyahyaei Z, et al. Extracellular vesicles and reproduction-promotion of successful pregnancy. Cell Mol Immunol. 2014; 11(6): 548–563.
  14. Ng YH, Rome S, Jalabert A, et al. Endometrial exosomes/microvesicles in the uterine microenvironment: a new paradigm for embryo-endometrial cross talk at implantation. PLoS One. 2013; 8(3): e58502.
  15. Noyes RW, Hertig AT, Rock J, et al. Dating the endometrial biopsy. Am J Obstet Gynecol. 1975; 122(2): 262–263.
  16. Thike AA, Chng MJ, Fook-Chong S, et al. Immunohistochemical expression of hormone receptors in invasive breast carcinoma: correlation of results of H-score with pathological parameters. Pathology. 2001; 33(1): 21–25.
  17. Ishibashi H, Suzuki T, Suzuki S, et al. Sex steroid hormone receptors in human thymoma. J Clin Endocrinol Metab. 2003; 88(5): 2309–2317.
  18. Hirsch FR, Varella-Garcia M, Bunn PA, et al. Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J Clin Oncol. 2003; 21(20): 3798–3807.
  19. John T, Liu G, Tsao MS. Overview of molecular testing in non-small-cell lung cancer: mutational analysis, gene copy number, protein expression and other biomarkers of EGFR for the prediction of response to tyrosine kinase inhibitors. Oncogene. 2009; 28 Suppl 1: S14–S23.
  20. Altmäe S, Koel M, Võsa U, et al. Meta-signature of human endometrial receptivity: a meta-analysis and validation study of transcriptomic biomarkers. Sci Rep. 2017; 7(1): 10077.
  21. Vilella F, Moreno-Moya JM, Balaguer N, et al. Hsa-miR-30d, secreted by the human endometrium, is taken up by the pre-implantation embryo and might modify its transcriptome. Development. 2015; 142(18): 3210–3221.
  22. Machtinger R, Laurent LC, Baccarelli AA. Extracellular vesicles: roles in gamete maturation, fertilization and embryo implantation. Hum Reprod Update. 2016; 22(2): 182–193.
  23. Saadeldin IM, Oh HJu, Lee BC. Embryonic-maternal cross-talk via exosomes: potential implications. Stem Cells Cloning. 2015; 8: 103–107.
  24. Evans J, Salamonsen LA, Winship A, et al. Fertile ground: human endometrial programming and lessons in health and disease. Nat Rev Endocrinol. 2016; 12(11): 654–667.
  25. Burns G, Brooks K, Wildung M, et al. Extracellular vesicles in luminal fluid of the ovine uterus. PLoS One. 2014; 9(3): e90913.
  26. Burnett LA, Nowak RA. Exosomes mediate embryo and maternal interactions at implantation and during pregnancy. Front Biosci (Schol Ed). 2016; 8: 79–96.
  27. Kropp J, Salih SM, Khatib H. Expression of microRNAs in bovine and human pre-implantation embryo culture media. Front Genet. 2014; 5: 91.
  28. Baig S, Lim JY, Fernandis AZ, et al. Lipidomic analysis of human placental syncytiotrophoblast microvesicles in adverse pregnancy outcomes. Placenta. 2013; 34(5): 436–442.
  29. Iwai M, Hamatani T, Nakamura A, et al. Membrane protein CD9 is repositioned and released to enhance uterine function. Lab Invest. 2019; 99(2): 200–209.
  30. Chaudhari-Kank M, Zaveri K, Antia V, et al. Comparison of CD9 & CD146 markers in endometrial stromal cells of fertile & infertile females. Indian Journal of Medical Research. 2018; 147(6): 552.

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