Amino acid profile of blood plasma and follicular fluid in women with infertility and diminished ovarian reserve
- Authors: Shevtsova M.A.1, Gavisova A.A.1, Krasnova N.A.1, Aksenenko A.A.1, Novoselova A.V.1, Khazzhar F.1, Chagovets V.V.1, Frankevich V.E.1
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Affiliations:
- Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation
- Issue: No 2 (2024)
- Pages: 79-88
- Section: Original Articles
- URL: https://journals.eco-vector.com/0300-9092/article/view/631357
- DOI: https://doi.org/10.18565/aig.2023.270
- ID: 631357
Cite item
Abstract
Objective: This study aimed to investigate the amino acid profiles of blood plasma and follicular fluid in women with infertility and diminished ovarian reserve.
Materials and methods: The study included 115 women aged 18–42 years with infertility, referred to as V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia for infertility treatment using ART (IVF/ICSI) and meeting the inclusion criteria. The groups were stratified according to ovarian reserve as follows: group 1 – 50 patients with diminished ovarian reserve (AMH <1.2 ng/ml, AFC<5); group 2 – 65 patients with normal ovarian reserve (AMH ≥1.2 ng/ml, AFC≥5) and matched for age. Analysis of amino acid levels in the blood plasma and follicular fluid on the day of oocyte aspiration was conducted using liquid chromatography with mass spectrometric detection.
Results: Analysis of the amino acid profile revealed a statistically significant decrease in sarcosine and tryptophan in women with diminished ovarian reserve compared to women with normal ovarian reserve. Additionally, there was a statistically significant decrease in the concentrations of lysine, asparagine, methionine, phenylalanine, and tryptophan in the follicular fluid of women with diminished ovarian reserve. Correlation analysis showed a strong correlation between amino acid levels in the plasma and follicular fluid, as well as between amino acid levels in the plasma and follicular fluid. It also revealed a moderate positive correlation between antral follicle counts and indicators of oogenesis and early embryogenesis, and the levels of amino acids, specifically lysine and sarcosine in blood plasma and asparagine, tryptophan, and aminobutyric acid in follicular fluid.
Conclusion: This study found a significant reduction in amino acid levels in infertile women with diminished ovarian reserve, which may serve as a marker for assessing ovarian reserve and oocyte development potential to enhance outcomes in ART programs.
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About the authors
Marina A. Shevtsova
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation
Author for correspondence.
Email: marina_981995@mail.ru
post-graduate student
Russian Federation, 117997, Moscow, Ac. Oparina str., 4Alla A. Gavisova
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation
Email: a_gavisova@oparina4.ru
Dr.Med. Sci., Head of the 1st Gynecology Department
Russian Federation, 117997, Moscow, Ac. Oparina str., 4Natalya A. Krasnova
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation
Email: dr.krasnova@rambler.ru
ORCID iD: 0000-0001-8636-2560
PhD, Teaching Assistant at the Department of Obstetrics, Gynecology, Perinatology and Reproductology
Russian Federation, 117997, Moscow, Ac. Oparina str., 4Artem A. Aksenenko
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation
Email: a_axenenko@oparina4.ru
PhD, Gynecologist at the 1st Gynecology Department
Russian Federation, 117997, Moscow, Ac. Oparina str., 4Anastasia V. Novoselova
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation
Email: a_novoselova@oparina4.ru
Researcher at the Laboratory of Metabolomics and Bioinformatics
Russian Federation, 117997, Moscow, Ac. Oparina str., 4Fadi Khazzhar
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation
Email: a_novoselova@oparina4.ru
PhD, Junior Researcher at the Laboratory of Metabolomics and Bioinformatics
Russian Federation, 117997, Moscow, Ac. Oparina str., 4Vitaliy V. Chagovets
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation
Email: vvchagovets@gmail.com
PhD (Physico-mathematical Sciences), Head of the Laboratory of Metabolomics and Bioinformatics
Russian Federation, 117997, Moscow, Ac. Oparina str., 4Vladimir E. Frankevich
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation
Email: v_vfrankevich@oparina4.ru
Dr.Sci. (Physico-mathematical Sciences), Deputy Director of the Institute of Translational Medicine
Russian Federation, 117997, Moscow, Ac. Oparina str., 4References
- Hu S., Xu B., Jin L. Perinatal outcome in young patients with diminished ovarian reserve undergoing assisted reproductive technology. Fertil. Steril. 2020; 114(1): 118-24.e1. https//dx.doi.org/10.1016/j.fertnstert.2020.02.112.
- Dumesic D.A., Meldrum D.R., Katz-Jaffe M.G., Krisher R.L., Schoolcraft W.B. Oocyte environment: follicular fluid and cumulus cells are critical for oocyte health. Fertil. Steril. 2015; 103(2): 303-16. https//dx.doi.org/10.1016/j.fertnstert.2014.11.015.
- Edwards R.G. Follicular fluid. J. Reprod. Fertil. 1974; 37(1): 189-219. https//dx.doi.org/10.1530/jrf.0.0370189.
- Klein N.A., Battaglia D.E., Miller P.B., Branigan E.F., Giudice L.C., Soules M.R. Ovarian follicular development and the follicular fluid hormones and growth factors in normal women of advanced reproductive age. J. Clin. Endocrinol. Metab. 1996; 81(5): 1946-51. https//dx.doi.org/10.1210/jcem.81.5.8626862.
- Revelli A., Delle Piane L., Casano S., Molinari E., Massobrio M., Rinaudo P. Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics. Reprod. Biol. Endocrinol. 2009; 7: 40. https//dx.doi.org/10.1186/1477-7827-7-40.
- Драпкина Ю.С., Тимофеева А.В., Чаговец В.В., Кононихин А.С., Франкевич В.Е., Калинина Е.А. Применение омиксных технологий в решении проблем репродуктивной медицины. Акушерство и гинекология. 2018; 9: 24-32. [Drapkina Yu.S., Timofeeva A.V., Chagovets V.V., Kononikhin A.S., Frankevich V.E., Kalinina E.A. Use of omics technologies to solve the problems of reproductive medicine. Obstetrics and Gynecology. 2018; (9): 24-32. (in Russian)]. https://dx.doi.org/10.18565/aig.2018.9.24-32.
- Wilson I.D., Theodoridis G., Virgiliou C. A perspective on the standards describing mass spectrometry-based metabolic phenotyping (metabolomics/metabonomics) studies in publications. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2021; 1164: 122515. https//dx.doi.org/10.1016/j.jchromb.2020.122515.
- Yang J., Feng T., Li S., Zhang X., Qian Y. Human follicular fluid shows diverse metabolic profiles at different follicle developmental stages. Reprod. Biol. Endocrinol. 2020; 18(1): 74. https//dx.doi.org/10.1186/s12958-020-00631-x.
- Liu L., Yin T.L., Chen Y., Li Y., Yin L., Ding J., Yang J., Feng H.L. Follicular dynamics of glycerophospholipid and sphingolipid metabolisms in polycystic ovary syndrome patients. J. Steroid Biochem. Mol. Biol. 2019; 185: 142-9. https//dx.doi.org/10.1016/j.jsbmb.2018.08.008.
- Karaer A., Tuncay G., Mumcu A., Dogan B. Metabolomics analysis of follicular fluid in women with ovarian endometriosis undergoing in vitro fertilization. Syst. Biol. Reprod. Med. 2019; 65(1): 39-47. https//dx.doi.org/10.1080/19396368.2018.1478469.
- Ярыгина С.А., Смольникова В.Ю., Калинина Е.А., Эльдаров Ч.М., Гамисония А.М., Макарова Н.П., Бобров М.Ю. Анализ метаболитов в различных средах культивирования эмбрионов человека. Акушерство и гинекология. 2020; 11: 114-23. [Yarygina S.A., Smolnikova V.Yu., Kalinina E.A., Eldarov Ch.M., Gamisonia A.M., Makarova N.P., Bobrov M.Yu. Analysis of human embryo culture medium metabolites. Obstetrics and Gynecology. 2020; (11): 114-23. (in Russian)]. https://dx.doi.org/10.18565/aig.2020.11.114-123.
- Sun Z., Chang H.M., Wang A., Song J., Zhang X., Guo J. et al. Identification of potential metabolic biomarkers of polycystic ovary syndrome in follicular fluid by SWATH mass spectrometry. Reprod. Biol. Endocrinol. 2019; 17(1): 45. https//dx.doi.org/10.1186/s12958-019-0490-y.
- Wu G. Amino acids: metabolism, functions, and nutrition. Amino Acids. 2009; 37(1): 1-17. https//dx.doi.org/10.1007/s00726-009-0269-0.
- https://upload.wikimedia.org/wikipedia/commons/c/ce/AminoAcidball.svg
- Palii S.S., Kays C.E., Deval C., Bruhat A., Fafournoux P., Kilberg M.S. Specificity of amino acid regulated gene expression: analysis of genes subjected to either complete or single amino acid deprivation. Amino Acids. 2009; 37(1): 79-88. https//dx.doi.org/10.1007/s00726-008-0199-2.
- Brosnan J.T. Amino acids, then and now--a reflection on Sir Hans Krebs' contribution to nitrogen metabolism. IUBMB Life. 2001; 52(6): 265-70. https//dx.doi.org/10.1080/152165401317291101.
- Newsholme P., Brennan L., Rubi B., Maechler P. New insights into amino acid metabolism, beta-cell function and diabetes. Clin. Sci. (Lond). 2005; 108(3): 185-94. https//dx.doi.org/10.1042/CS20040290.
- Wu G., Bazer F.W., Davis T.A., Kim S.W., Li P., Marc Rhoads J. et al. Arginine metabolism and nutrition in growth, health and disease. Amino Acids. 2009; 37(1): 153-68. https//dx.doi.org/10.1007/s00726-008-0210-y.
- Wu G., Bazer F.W., Datta S., Johnson G.A., Li P., Satterfield M.C., Spencer T.E. Proline metabolism in the conceptus: implications for fetal growth and development. Amino Acids. 2008; 35(4): 691-702. https//dx.doi.org/10.1007/s00726-008-0052-7.
- Министерство здравоохранения Российской Федерации. Клинические рекомендации «Женское бесплодие». 2021. [Ministry of Health of the Russian Federation. Clinical guidelines "Female infertility". 2021. (in Russian)].
- Misra B.B. Data normalization strategies in metabolomics: Current challenges, approaches, and tools. Eur. J. Mass Spectrom. (Chichester). 2020; 26(3):165-74. https//dx.doi.org/10.1177/1469066720918446.
- Li J., Zhang Z., Wei Y., Zhu P., Yin T., Wan Q. Metabonomic analysis of follicular fluid in patients with diminished ovarian reserve. Front. Endocrinol. 2023; 14: 1132621. https//dx.doi.org/10.3389/fendo.2023.1132621.
- Baković P., Kesić M., Perić M., Bečeheli I., Horvatiček M., George M. et al. Differential serotonin uptake mechanisms at the human maternal-fetal interface. Int. J. Mol. Sci. 2021; 22(15): 7807. https//dx.doi.org/10.3390/ijms22157807.
- Dubé F., Amireault P. Local serotonergic signaling in mammalian follicles, oocytes and early embryos. Life Sci. 2007; 81(25-26): 1627-37. https//dx.doi.org/10.1016/j.lfs.2007.09.034.
- D'Aniello G., Grieco N., Di Filippo M.A., Cappiello F., Topo E., D'Aniello E., Ronsini S. Reproductive implication of D-aspartic acid in human pre-ovulatory follicular fluid. Hum. Reprod. 2007; 22(12): 3178-83. https//dx.doi.org/10.1093/humrep/dem328.