Development and testing of an endometrial status assessment test based on RNAampliSeq technology

Cover Page


Cite item

Full Text

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

Abstract

BACKGROUND: Approximately two thirds of all implantation failures are due to impaired endometrial receptivity. The lack of implantation may be due to an implantation window failure found in approximately 25-30% of women with a history of failure to perform assisted reproductive technology protocols. The receptivity phase in such patients can be shifted in terms of timing, have a short duration, or not form. Currently, there are several commercial tests for determining endometrial receptivity based on transcriptomic data. However, these tests differ very significantly from each other in the set of genes studied, and the exact mechanism of endometrial receptivity is still not fully understood.

AIM: The aim of this study was to create and check our own test based on RNA AmpliSeq technology to assess the receptivity status of the endometrium and the implantation window.

MATERIALS AND METHODS: We previously created an RNAampliSeq panel containing 421 gens. With its use, the differential expression of these genes was analyzed in 38 endometrial samples taken in the proliferative and receptive phases.

RESULTS: The studied samples form clearly distinguishable clusters with the receptive and proliferative endometria. 271 genes from our panel are differentially expressed in different phases of the menstrual cycle.

CONCLUSIONS: We have created and tested a model that allows clearly distinguishing between the proliferative endometrium and the receptive one and identifying patients with disorders of the menstrual cycle.

Full Text

Restricted Access

About the authors

Olga V. Malysheva

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: omal99@mail.ru
ORCID iD: 0000-0002-8626-5071
SPIN-code: 1740-2691

Cand. Sci. (Biol.)

Russian Federation, Saint Petersburg

Elena S. Vashukova

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: vi_lena@list.ru
ORCID iD: 0000-0002-6996-8891
SPIN-code: 2811-8730

Cand. Sci. (Biol.)

Russian Federation, Saint Petersburg

Alexander M. Gzgzyan

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: agzgzyan@gmail.com
ORCID iD: 0000-0003-3917-9493
SPIN-code: 6412-4801

MD, Dr. Sci. (Med.)

Russian Federation, Saint Petersburg

Lyailya Kh. Dzhemlikhanova

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: dzhemlikhanova_l@mail.ru
ORCID iD: 0000-0001-6842-4430
SPIN-code: 1691-6559

MD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg

Ksenia V. Ob'edkova

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: iagmail@ott.ru
ORCID iD: 0000-0002-2056-7907
SPIN-code: 2709-2890

MD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg

Anastasiia K. Popova

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: stassi1997@mail.ru
ORCID iD: 0009-0008-3512-2557
Russian Federation, Saint Petersburg

Alexander A. Tkachenko

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: castorfiber@list.ru
ORCID iD: 0000-0001-7985-0216
Russian Federation, Saint Petersburg

Maria A. Shalina

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Author for correspondence.
Email: amarus@inbox.ru
ORCID iD: 0000-0002-5921-3217
SPIN-code: 6673-2660

MD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg

Maria I. Yarmolinskaya

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: m.yarmolinskaya@gmail.com
ORCID iD: 0000-0002-6551-4147
SPIN-code: 3686-3605

MD, Dr. Sci. (Med.), Professor of the Russian Academy of Sciences

Russian Federation, Saint Petersburg

Andrey S. Glotov

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: anglotov@mail.ru
ORCID iD: 0000-0002-7465-4504
SPIN-code: 1406-0090

Dr. Sci. (Biol.)

Russian Federation, Saint Petersburg

References

  1. Achache H, Revel A. Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update. 2006;12(6):731–746. doi: 10.1093/humupd/dml004
  2. Haouzi D, Dechaud H, Assou S, et al. Insights into human endometrial receptivity from transcriptomic and proteomic data. Reprod Biomed Online. 2012;24(1):23–34. doi: 10.1016/j.rbmo.2011.09.009
  3. Lessey BA, Young SL. What exactly is endometrial receptivity? Fertil Steril. 2019;111(4):611–617. doi: 10.1016/j.fertnstert.2019.02.009
  4. Bai X, Zheng L, Li D, et al. Research progress of endometrial receptivity in patients with polycystic ovary syndrome: a systematic review. Reprod Biol Endocrinol. 2021;19(1):122. doi: 10.1186/s12958-021-00802-4
  5. Enciso M, Aizpurua J, Rodríguez-Estrada B, et al. The precise determination of the window of implantation significantly improves ART outcomes. Sci Rep. 2021;11(1):13420. doi: 10.1038/s41598-021-92955-w
  6. Díaz-Gimeno P, Horcajadas JA, Martínez-Conejero JA, et al. A genomic diagnostic tool for human endometrial receptivity based on the transcriptomic sDiazignature. Fertil Steril. 2011;95(1):50–60. doi: 10.1016/j.fertnstert.2010.04.063
  7. Ruiz-Alonso M, Blesa D, Simón C. The genomics of the human endometrium. Biochim Biophys Acta. 2012;1822(12):1931–1942. doi: 10.1016/j.bbadis.2012.05.004
  8. Ruiz-Alonso M, Blesa D, Díaz-Gimeno P, et al. The endometrial receptivity array for diagnosis and personalized embryo transfer as a treatment for patients with repeated implantation failure. Fertil Steril. 2013;100(3):818–824. doi: 10.1016/j.fertnstert.2013.05.004
  9. Kibanov MV, Makhmudova GM, Gokhberg YA. In search for an ideal marker of endometrial receptivity: from histology to comprehensive molecular genetics-based approaches. Almanac of Clinical Medicine. 2019;47(1):12–25. doi: 10.18786/2072-0505-2019-47-005
  10. Coutifaris C, Myers ER, Guzick DS, et al.; NICHD National Cooperative Reproductive Medicine Network. Histological dating of timed endometrial biopsy tissue is not related to fertility status. Fertil Steril. 2004;82(5):1264–1272. doi: 10.1016/j.fertnstert.2004.03.069
  11. Murray MJ, Meyer WR, Zaino RJ, et al. A critical analysis of the accuracy, reproducibility, and clinical utility of histologic endometrial dating in fertile women. Fertil Steril. 2004;81(5):1333–1343. doi: 10.1016/j.fertnstert.2003.11.030
  12. Ruiz-Alonso M, Valbuena D, Gomez C, et al. Endometrial Receptivity Analysis (ERA): data versus opinions. Hum Reprod Open. 2021;2021(2). doi: 10.1093/hropen/hoab011
  13. 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). doi: 10.1038/s41598-017-10098-3
  14. Haouzi D, Entezami F, Torre A, et al. Customized frozen embryo transfer after identification of the receptivity window with a transcriptomic approach improves the implantation and live birth rates in patients with repeated implantation failure. Reprod Sci. 2021;28(1):69–78. doi: 10.1007/s43032-020-00252-0
  15. Gómez E, Ruíz-Alonso M, Miravet J, et al. Human endometrial transcriptomics: implications for embryonic implantation. Cold Spring Harb Perspect Med. 2015;5(7). doi: 10.1101/cshperspect.a022996
  16. Predeus AV, Vashukova ES, Glotov AS, et al. Next-generation sequencing of matched ectopic and eutopic endometrium identifies novel endometriosis-related genes. Russ J Genet. 2018;54(11): 1358–1365. doi: 10.1134/S1022795418110133
  17. Altmäe S, Esteban FJ, Stavreus-Evers A, et al. Guidelines for the design, analysis and interpretation of ‘omics’ data: focus on human endometrium. Hum Reprod Update. 2014;20(1):12–28. doi: 10.1093/humupd/dmt048
  18. Horcajadas JA, Pellicer A, Simón C. Wide genomic analysis of human endometrial receptivity: new times. New opportunities. Hum Reprod Update. 2007;13(1):77–86. doi: 10.1093/humupd/dml046
  19. Zhang L, Liu X, Liu J, et al. The developmental transcriptome landscape of receptive endometrium during embryo implantation in dairy goats. Gene. 2017;633:82–95. doi: 10.1016/j.gene.2017.08.026
  20. Franasiak JM, Burns KA, Slayden O, et al. Endometrial CXCL13 expression is cycle regulated in humans and aberrantly expressed in humans and Rhesus macaques with endometriosis. Reprod Sci. 2015;22(4):442–451. doi: 10.1177/1933719114542011
  21. Ohye H, Sugawara M. Dual oxidase, hydrogen peroxide and thyroid diseases. Exp Biol Med (Maywood). 2010;235(4):424–433. doi: 10.1258/ebm.2009.009241
  22. Pathak BR, Breed AA, Apte S, et al. Cysteine-rich secretory protein 3 plays a role in prostate cancer cell invasion and affects expression of PSA and ANXA1. Mol Cell Biochem. 2016;411(1-2):11–21. doi: 10.1007/s11010-015-2564-2
  23. Su MT, Huang JY, Tsai HL, et al. A common variant of PROK1 (V67I) acts as a genetic modifier in early human pregnancy through down-regulation of gene expression. Int J Mol Sci. 2016;17(2):162. doi: 10.3390/ijms17020162
  24. Macdonald LJ, Sales KJ, Grant V, et al. Prokineticin 1 induces Dickkopf 1 expression and regulates cell proliferation and decidualization in the human endometrium. Mol Hum Reprod. 2011;17(10):626–636. doi: 10.1093/molehr/gar031
  25. Chen L, Xiao D, Tang F, et al. CAPN6 in disease: an emerging therapeutic target (review). Int J Mol Med. 2020;46(5):1644–1652. doi: 10.3892/ijmm.2020.4734
  26. Allegra A, Marino A, Coffaro F, et al. Is there a uniform basal endometrial gene expression profile during the implantation window in women who became pregnant in a subsequent ICSI cycle? Hum Reprod. 2009;24(10):2549–2257. doi: 10.1093/humrep/dep222
  27. Talbi S, Hamilton AE, Vo KC, et al. Molecular phenotyping of human endometrium distinguishes menstrual cycle phases and underlying biological processes in normo-ovulatory women. Endocrinology. 2006;147(3):1097–1121. doi: 10.1210/en.2005-1076
  28. Liu LJ, Liao JM, Zhu F. Proliferating cell nuclear antigen clamp associated factor, a potential proto-oncogene with increased expression in malignant gastrointestinal tumors. World J Gastrointest Oncol. 2021;13(10):1425–1439. doi: 10.4251/wjgo.v13.i10.1425
  29. Xu Z, Ye J, Bao P, et al. Long non-coding RNA SNHG3 promotes the progression of clear cell renal cell carcinoma via regulating BIRC5 expression. Transl Cancer Res. 2021;10(10):4502–4513. doi: 10.21037/tcr-21-1802
  30. Jin Z, Peng F, Zhang C, et al. Expression, regulating mechanism and therapeutic target of KIF20A in multiple cancer. Heliyon. 2023;9(2). doi: 10.1016/j.heliyon.2023.e13195

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Appendix
Download (197KB)
3. Fig. 1. Principal component analysis of expression profiles in proliferative and receptive endometrium samples

Download (176KB)
4. Fig. 2. Principal component analysis of expression profiles in endometrial samples from patients with or without adenomyosis

Download (127KB)
5. Fig. 3. MA plot of mean differentially expressed genes in receptive and proliferative endometrium samples (p < 0.05)

Download (144KB)
6. Fig. 4. Hierarchical clustering of 38 endometrial samples. Samples are presented vertically and expression values horizontally. Color indicates the intensity of gene expression values (red, high; blue, low)

Download (474KB)

Copyright (c) 2023 Eсо-Vector

License URL: https://eco-vector.com/for_authors.php#07

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 66759 от 08.08.2016 г. 
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия Эл № 77 - 6389
от 15.07.2002 г.



This website uses cookies

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

About Cookies