ISSN 0300-9092 (Print)
ISSN 2412-5679 (Online)

Amino acid composition of the endometrium in patients with diminished ovarian reserve

Dubinskaya E.D., Mglinets A.P., Gasparov A.S., Alyoshkina E.V.

Patrice Lumumba Peoples' Friendship University of Russia, Moscow, Russia

Objective. To determine the characteristics of the endometrial amino acid profile in patients with diminished ovarian reserve (DOR) compared with patients with normal ovarian reserve in early and middle reproductive age.
Materials and methods. An observational cross-sectional comparative study was conducted in 110 reproductive-age patients (20–35 years) undergoing preparation for assisted reproductive technology (ART) programs. Patients were divided into two groups: group 1 comprised 80 patients with DOR (AMH<1.2 ng/mL, AFC<5–7 in each ovary); group 2 (control) comprised 30 patients with normal ovarian reserve. Endometrial samples were obtained by pipelle biopsy during the mid-secretory phase of the menstrual cycle. Twenty-three amino acids and their metabolites were analyzed using UPLC-MS/MS). Statistical analyses were performed using the MetaboAnalyst v5.0 platform and included univariate analysis (Mann–Whitney U test, FDR) and multivariate statistical analysis (PCA, PLS-DA), as well as metabolic pathway analysis.
Results. Statistically significant differences were identified for 11 amino acids (q<0.05). Patients with DOR showed marked reductions in sarcosine concentration (7.91-fold; FC=0.13), tryptophan (FC=0.68), pipecolic acid (FC=0.76), and leucine (FC=0.89). At the same time, increased levels of alanine (FC=1.64), γ-aminobutyric acid (FC=1.61), asparagine (FC=1.56), glutamine (FC=1.55), proline (FC=1.44), hydroxyproline (FC=1.17), and aspartic acid (FC=1.15) were observed. Multivariate PLS-DA demonstrated clear separation of the groups based on their metabolic profiles. The most pronounced changes involved the alanine, aspartate and glutamate, and arginine and proline metabolic pathways.
Conclusion. DOR in patients of early and middle reproductive age is associated with the development of a local metabolic phenotype of the endometrium characterized by alterations in amino acid composition. These changes may be associated with the functional state of the endometrium and its implantation potential.

Authors' contributions. Dubinskaya E.D. – conception and design of the study, scientific supervision, editing of the manuscript; Mglinets A.P. – data collection and analysis, statistical analysis, literature review, drafting of the manuscript; Gasparov A.S. – consultation, editing of the manuscript; Alyoshkina E.V. – data processing and drafting of the manuscript.
Conflicts of interest. The authors have no conflicts of interest to declare.
Funding. There was no funding for this study.
Ethical Approval: The study was reviewed and approved by the Research Ethics Committee of the Patrice Lumumba Peoples' Friendship University of Russia (Ref. No: 4).
Generative Artificial Intelligence. No artificial intelligence tools were used in the preparation of this manuscript.
Patient Consent for Publication. All patients provided informed consent for the publication of their data.
Authors' Data Sharing Statement. The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.
For citation: Dubinskaya E.D., Mglinets A.P., Gasparov A.S., Alyoshkina E.V. Amino acid composition
of the endometrium in patients with diminished ovarian reserve.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2026; (10): 89-99 (in Russian)
https://dx.doi.org/10.18565/aig.2026.293

Keywords

endometrium
endometrial receptivity
amino acid composition
diminished ovarian reserve
metabolomics

References

  1. Choi R., Park W., Chun G., Lee S.G., Lee E.H. Investigation of the prevalence of diminished ovarian reserve in Korean women of reproductive age. J. Clin. Med. 2023; 12(15): 5099. https://dx.doi.org/10.3390/jcm12155099
  2. Carson S.A., Kallen A.N. Diagnosis and management of infertility: a review. JAMA. 2021; 326(1): 65-76. https://dx.doi.org/10.1001/jama.2021.4788
  3. Liu F.X., Ming H.X., Huang K.L., Yi S.J., Liang X.F., Luo W.W. et al. Clinical pregnancy outcomes in young women with diminished ovarian reserve undergoing frozen embryo transfer: a comprehensive analysis with exploratory insights into endometrial aging. Front. Endocrinol. (Lausanne). 2025; 16: 1608200. https://dx.doi.org/10.3389/fendo.2025.1608200
  4. Zhu S., Jiang W., Liao X., Sun Y., Chen X., Zheng B. Effect of diminished ovarian reserve on the outcome of fresh embryo transfer in IVF/ICSI cycles among young women: a retrospective cohort study. BMC Womens Health. 2024; 24(1): 230. https://dx.doi.org/10.1186/s12905-024-03039-6
  5. Li H.J., Seifer D.B., Tal R. AMH independently predicts aneuploidy but not live birth per transfer in IVF PGT-A cycles. Reprod. Biol. Endocrinol. 2023; 21(1): 19. https://dx.doi.org/10.1186/s12958-023-01066-w
  6. Eubanks A., Flannagan K., Le K., Namath A., Rambhatla A., Reckhow J. et al. Beyond numbers: antimüllerian hormone and antral follicle count are not independent predictors of embryo euploidy in in vitro fertilization with preimplantation genetic testing for aneuploidy. Fertil. Steril. 2026; 125(2): 237-46. https://dx.doi.org/10.1016/j.fertnstert.2025.08.013
  7. Дубинская Е.Д., Гаспаров А.С., Мглинец А.П., Лукьянова Я.С.,Мацкевич Е.Н. Клинико-анамнестические предикторы неудач имплантации при низком овариальном резерве: ретроспективное исследование. Акушерство и гинекология. 2026; 5: 140-7. https://dx.doi.org/10.18565/aig.2026.58 [Dubinskaya E.D., Gasparov A.S., Mglinets A.P., Lukyanova Ya.S., Matskevich E.N. Clinical and anamnestic predictors of implantation failures in women with diminished ovarian reserve: retrospective study. Obstetrics and Gynecology. 2026; (5): 140-7 (in Russian). https://dx.doi.org/10.18565/aig.2026.58].
  8. Радзинский В.Е., Михалёва Л.М., Оразов М.Р., Силантьева Е.С., Камилова Д.П., Мидибер К.Ю., Орехов Р.Е. Рецептивность эндометрия пациенток с повторными неудачами имплантации. Доктор.Ру. 2022; 21(1): 27-33. https://dx.doi.org/10.31550/1727-2378-2022-21-1-27-33 [Radzinsky V.E., Mikhaleva L.M., OrazovM.R., Silantieva E.S., Kamilova D.P., Midiber K.Yu., Orekhov R.E. Endometrium receptivity in patients with repeated implant failures. Doctor.ru. 2022; 21(1): 27-33 (in Russian). https://dx.doi.org/10.31550/1727-2378-2022-21-1-27-33].
  9. Hiraoka T., Osuga Y., Hirota Y. Current perspectives on endometrial receptivity: a comprehensive overview of etiology and treatment. J. Obstet. Gynaecol. Res. 2023; 49(10): 2397-409. https://dx.doi.org/10.1111/jog.15759
  10. Molina N.M., Jurado-Fasoli L., Sola-Leyva A., Sevilla-Lorente R., Canha-Gouveia A., Ruiz-Durán S. et al. Endometrial whole metabolome profile at the receptive phase: influence of Mediterranean Diet and infertility. Front. Endocrinol. (Lausanne). 2023; 14: 1120988. https://dx.doi.org/10.3389/fendo.2023.1120988
  11. Gao J., Xiao Y. Metabolomics and its applications in assisted reproductive technology. IET Nanobiotechnol. 2023; 17(5): 399-405. https://dx.doi.org/10.1049/nbt2.12141
  12. Wang J., Zenere A., Wang X., Bergström G., Edfors F., Uhlén M. et al. Longitudinal analysis of genetic and environmental interplay in human metabolic profiles and the implication for metabolic health. Genome Med. 2025; 17: 68. https://dx.doi.org/10.1186/s13073-025-01492-y
  13. Ling Z.N., Jiang Y.F., Ru J.N., Lu J.H., Ding B., Wu J. Amino acid metabolism in health and disease. Signal Transduct. Target Ther. 2023; 8(1): 345. https://dx.doi.org/10.1038/s41392-023-01569-3
  14. Shu Q., Zhao Y., Wang A., Li W., Xu H., Dong W. et al. [Analysis of the difference in metabolites and gene expressions between pre-receptive and receptive endometria]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2023; 40(12): 1496-503. https://dx.doi.org/10.3760/cma.j.cn511374-20221108-00769
  15. Ferraretti A.P., La Marca A., Fauser B.C.J.M., Tarlatzis B., Nargund G., Gianaroli L. ESHRE consensus on the definition of “poor response” to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum. Reprod. 2011; 26(7): 1616-24. https://dx.doi.org/10.1093/humrep/der092
  16. Wang M.J., Lin M.H., Yang J.H., Lee R.K.-K., Lee K.S. Low antimüllerian hormone (<1.2 ng/ml) does not impact oocyte quality and IVF/ICSI outcomes in women ≤40 years old. Taiwan. J. Obstet. Gynecol. 2025; 64(2): 248-52. https://dx.doi.org/10.1016/j.tjog.2024.02.007
  17. Harden S.L., Zhou J., Gharanei S., Diniz-da-Costa M., Lucas E.S., Cui L. et al. Exometabolomic analysis of decidualizing human endometrial stromal and perivascular cells. Front. Cell. Dev. Biol. 2021; 9: 626619. https://dx.doi.org/10.3389/fcell.2021.626619
  18. Adamczyk M., Wender-Ozegowska E., Kedzia M. Epigenetic factors in eutopic endometrium in women with endometriosis and infertility. Int. J. Mol. Sci. 2022; 23(7): 3804. https://dx.doi.org/10.3390/ijms23073804
  19. Panagodimou E., Terzopoulou I., Triantafyllidou O., Markantes G., Georgopoulos N., Vlahos N. et al. The role of immunologic factors in endometrial receptivity: an embryo-endometrium dialogue. Int. J. Mol. Sci. 2026; 27(10): 4588. https://dx.doi.org/10.3390/ijms27104588
  20. Gebril M., Mulder S., Das R., Nallasamy S. Extracellular matrix reorganization during endometrial decidualization. Histochem. Cell. Biol. 2025; 163(1): 84. https://dx.doi.org/10.1007/s00418-025-02411-3
  21. Jia Z., Wei Y., Zhang Y., Song K., Yuan J. Metabolic reprogramming and heterogeneity during the decidualization process of endometrial stromal cells. Cell. Commun. Signal. 2024; 22(1): 385. https://dx.doi.org/10.1186/s12964-024-01763-y
  22. Liu X., Xu S-j. Research progress in metabolomics for assessing endometrial receptivity in women with repeated implantation failure. Journal of International Obstetrics and Gynecology. 2026; 53(2): 165-9. https://dx.doi.org/10.12280/gjfckx.20251189
  23. Tang L., Xu X.H., Xu S., Liu Z., He Q., Li W. et al. Dysregulated Gln-Glu-α-ketoglutarate axis impairs maternal decidualization and increases the risk of recurrent spontaneous miscarriage. Cell. Rep. Med. 2023; 4(5): 101026. https://dx.doi.org/10.1016/j.xcrm.2023.101026
  24. Neill G., Masson G.R. A stay of execution: ATF4 regulation and potential outcomes for the integrated stress response. Front. Mol. Neurosci. 2023; 16: 1112253. https://dx.doi.org/10.3389/fnmol.2023.1112253
  25. Ducker G.S., Rabinowitz J.D. One-carbon metabolism in health and disease. Cell. Metab. 2017; 25(1): 27-42. https://dx.doi.org/10.1016/j.cmet.2016.08.009
  26. Kong S., Zhou C., Bao H., Ni Z., Liu M., He B. et al. Epigenetic control of embryo-uterine crosstalk at peri-implantation. Cell. Mol. Life Sci. 2019; 76(24): 4813-28. https://dx.doi.org/10.1007/s00018-019-03245-8
  27. Yue S., Li G., He S., Li T. The Central role of mTORC1 in amino acid sensing. Cancer Res. 2022; 82(17): 2964-74. https://dx.doi.org/10.1158/0008-5472.CAN-21-4403
  28. Seo S.K., Kwon B. Immune regulation through tryptophan metabolism. Exp. Mol. Med. 2023; 55(7): 1371-9. https://dx.doi.org/10.1038/s12276-023-01028-7
  29. Kovaříková V., Špirková A., Šefčíková Z., Pisko J., Kalatová L., Koppel J. et al. Gamma-aminobutyric acid (GABA) can affect physiological processes in preimplantation embryos via GABAA and GABAB receptors. Reprod. Med. Biol. 2023; 22(1): e12528. https://dx.doi.org/10.1002/rmb2.12528
  30. Chen W., Zhang Q., Wang H., Tan D., Tan Y. Unique and independent role of the GABAB1 subunit in embryo implantation and uterine decidualization in mice. Genes. Dis. 2019; 8(1): 79-86. https://dx.doi.org/10.1016/j.gendis.2019.06.005

Received 01.09.2026

Accepted 14.09.2026

About the Authors

Ekaterina D. Dubinskaya, Dr. Med. Sci., Professor at the Department of Obstetrics, Gynecology with a Course in Perinatology, Medical Institute, Patrice Lumumba Peoples’ Friendship University of Russia, 8 Miklukho-Maklaya str., Moscow, 117198, Russia, +7(903)117-55-58, eka-dubinskaya@yandex.ru, https://orcid.org/0000-0002-8311-0381
Anna P. Mglinets, PhD Student, Department of Obstetrics, Gynecology with a Course in Perinatology, Medical Institute, Patrice Lumumba Peoples’ Friendship University
of Russia, 8 Miklukho-Maklaya str., Moscow, 117198, Russia, +7(906)056-49-98, mg.anna@mail.ru, https://orcid.org/0009-0001-3985-3954
Alexander S. Gasparov, Dr. Med. Sci., Professor, Professor at the Department of Obstetrics, Gynecology with a Course in Perinatology, Medical Institute, Patrice Lumumba Peoples’ Friendship University of Russia, 8 Miklukho-Maklaya str., Moscow, 117198, Russia, +7(985)776-77-78, 13513520@mail.ru, https://orcid.org/0000-0001-6301-1880
Elizaveta V. Alyoshkina, Teaching Assistant at the Department of Obstetrics, Gynecology with a Course in Perinatology, Medical Institute, Patrice Lumumba Peoples’ Friendship University of Russia, 8 Miklukho-Maklaya str., Moscow, 117198, Russia, +7(926)768-44-27, alyoshkina.ev@yandex.ru, https://orcid.org/0000-0001-5339-1285

Similar Articles