Significance of glutathione peroxidases in endometrium function: facts, hypotheses, and research perspectives

Cover Page


Enzymes of glutathione peroxidase (GPX) family, together with peroxiredoxins, form thiol peroxidase superfamily, the property of which is the thiol-dependent catalysis of the hydroperoxide reduction. This property determines them as antioxidant protectors. Among human GPXs the eight forms are known, five of which are selenium-dependent (GPX1,2,3,4, and 6). The most number of facts supporting the substantial role of GPX in functioning of endometrium are linked with the GPX3, which is the secretory GPX. The number of candidate progesterone response elements in the promoter of GPX3 gene prevails over the number of candidate estrogen response elements; GPX3 is upregulated gene during postovulatory phase of reproductive cycle and during pregnancy; in the endometrial stroma, the transcription of Gpx3 is stimulated through the transcription factor HIF1α. Using laboratory animals, the spatial and temporal coincidence of Gpx3 activation and blastocyst implantation was observed. It was confirmed that GPX3 decreases hydrogen peroxide concentration in endometrium in pregnant animals and during in vitro decidualization. The vulnerability of reproductive function to physiological stress at the insufficient expression of GPX3 is hypothesized. The GPX3 enzymatic activity in endometrium is poorly investigated. The has been hypothesized that selenium-containing medications are effective in the endometrium receptivity improvement and in the supporting the normal embryo development (especially during the influence of physiological stressors) by the maintenance of the posttranscriptional, selenium-dependent stage of GPX3 biosynthesis in endometrium. Probably, the GPX3 expression can be increased by the steriods with gestagenic activity (through the increase of Gpx3 transcription, analogously to effect of progesterone). In contrast with the «classic» GPX (GPX1) and probably with most of other members of GPX family, GPX3 has a wide thiol specificity. It is proposed to assess the activity of GPX3 using the reduced homocysteine and cysteine as thiol substrates instead of the reduced glutathione.

Alexey V Razygraev

St Petersburg State Chemical-Pharmaceutical Academy

Author for correspondence.

Russian Federation, Saint Peterburg, Russia

scientific researcher

Mariya O Matrosova

Peter the Great Saint Petersburg Polytechnic University


Russian Federation, Saint Peterburg, Russia


Irina A Titovich

St Petersburg State Chemical-Pharmaceutical Academy


Russian Federation, Saint Peterburg, Russia

graduate student

  • Flohé L, Brigelius-Flohé R. Selenoproteins of the glutathione peroxidase family. In: Yatfield DL, et al. (Éd.) Selenium: Its Molecular Biology and Role in Human Health. New York: Springer; 2012. P. 167-180. doi: 10.1007/978-1-4614-1025-6_13.
  • Mittapalli O, Neal JJ, Shukle RH. Antioxidant defense response in a galling insect. PNAS. 2007;104(6):1889-94. doi: 10.1073/pnas.0604722104.
  • Torres WH. Biología de las especies de oxigeno reactivas. Mensaje Bioquimico. 2002;26:19-54.
  • Меньщикова Е.Б., Ланкин В.З., Зенков Н.К., и др. Окислительный стресс. Прооксиданты и антиоксиданты. – М.: Слово, 2006. [Men’shhikova EB, Lankin VZ, Zenkov NK, et al. Okislitel’nyj stress. Prooksidanty i antioksidanty. Moscow: Slovo; 2006. (In Russ.)]
  • Brigelius-Flohé R, Maiorino M. Glutathione peroxidases. Biochimica et Biophysica Acta. 2013;1830(5):3289-3303. doi: 10.1016/j.bbagen.2012.11.020.
  • Chu FF, Doroshow JH, Esworthy RS. Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI. J Biol Chem. 1993;268(4):2571-2576.
  • Avissar N, Ornt DB, Yagil Y, et al. Human kidney proximal tubules are the main source of plasma glutathione peroxidase. Am J Physiol. 1994;266(2):367-375.
  • Okamura N, Iwaki Y, Hiramoto S, et al. Molecular cloning and characterization of the epididymis-specific glutathione peroxidase-like protein secreted in the porcine epididymal fluid. Biochimica et Biophysica Acta (BBA)-General Subjects. 1997;1336(1):99-109. doi: 10.1016/S0304-4165(97)00016-0.
  • Takebe G, Yarimuzu J, Saito Y, et al. A comparative study on the hydroperoxide and thiol specificity of the glutathione peroxidase family and selenoprotein P. J Biol Chem. 2002;277(43):41254-8. doi: 10.1074/jbc.M202773200.
  • Разыграев А.В., Таборская К.И., Петросян М.А., Тумасова Ж.Н. Тиолпероксидазные активности плазмы крови крыс, определяемые с использованием пероксида водорода и 5,5’-дитиобис(2-нитробензойной кислоты) // Биомедицинская химия. – 2016. – Т. 62. – № 4. – С. 431–438. [Razygraev AV, Taborskaya KI, Petrosyan MA, Tumasova ZhN. Thiol peroxidase activities in rat blood plasma determined with hydrogen peroxide and 5,5’-dithio-bis (2-nitrobenzoic acid). Biomed Khim. 2016;62(4):431-8. (In Russ.)] doi: 10.18097/PBMC20166204431.
  • Wendel A. Glutathione peroxidase. In: Jakoby WB. (Ed.) Enzymatic Basis of Detoxication. V. 1. N.Y.: Academic Press; 1980. P. 333-353.
  • Zakowski JJ, Tappel AL. A semiautomated system for measurement of glutathione in the assay of glutathione peroxidase. Anal Biochem. 1978;89(2):430-436.
  • Колесниченко Л.С., Кулинский В.И. Глутатионтрансферазы // Успехи современной биологии. –1989. – Т. 107. – С. 179–194. [Kolesnichenko LS, Kulinskij VI. Glutationtransferazy. Uspekhi sovremennoj biologii. 1989;107:179-194. (In Russ.)]
  • Hurst R, Bao Y, Ridley S. Williamson G. Phospholipid hydroperoxide cysteine peroxidase activity of human serum albumin. Biochem J. 1999;338:723-728.
  • Saito Y, Hayashi T, Tanaka T, et al. Selenoprotein P in human plasma as an extracellular phospholipid hydroperoxide glutathione peroxidase. Isolation and enzymatic characterization of human selenoprotein P. J Biol Chem. 1999;274:2866-2871. doi: 10.1074/jbc.274.5.2866.
  • Borthwick JM, Charnock Jones DS, Tom BD, et al. Determination of the transcript profile of human endometrium. Mol Hum Reprod. 2003;9(1):19-33.
  • Horcajadas JA, Riesewijk A, Polman J, et al. Effect of controlled ovarian hyperstimulation in IVF on endometrial gene expression profiles. Mol Hum Reprod. 2004;11(3):195-205.
  • Horcajadas JA, Mínguez P, Dopazo J, et al. Controlled ovarian stimulation induces a functional genomic delay of the endometrium with potential clinical implications. J Clin Endocrinol Metab. 2008;93(11):4500-4510. doi: 10.1210/jc.2008-0588.
  • Ponnampalam AP, Weston GC, Trajstman AC, et al. Molecular classification of human endometrial cycle stages by transcriptional profiling. Mol Hum Reprod. 2004;10(12):879-893. doi: 10.1093/molehr/gah121.
  • Riesewijk A, Martín J, van OsR, et al. Gene expression profiling of human endometrial receptivity on days LH+ 2 versus LH+ 7 by microarray technology. Mol Hum Reprod. 2003;9(5):253-264. doi: 10.1093/molehr/gag037.
  • Kingsley PD, Whitin JC, Cohen HJ, Pails J. Developmental expression of extracellular glutathione peroxidase suggests antioxidant roles in deciduum, visceral yolk sac and skin. Mol Reprod Dev. 1998;44:343-355.
  • Ota H, Igarashi S, Kato N, Tanaka T. Aberrant expression of glutathione peroxidase in eutopic and ectopic endometrium in endometriosis and adenomyosis. Fertil Steril. 2000;74:313-318. doi: 10.1016/S0015-0282(00)00638-5.
  • Xu X, Leng JY, Gao F, et al. Differential expression and antioxidant function of glutathione peroxidase 3 in mouse uterus during decidualization. FEBS Letters. 2014;588(9):1580-9. doi: 10.1016/j.febslet.2014.02.043.
  • Christofferson RH, Wassberg BE, Nilsson BO. Angiogenesis in the rat uterus during pregnancy. In: S.R. Glasser et al. (Ed.) Endocrinology of Embryo-Endometrium Interactions. Springer US; 1994. P. 77-92.
  • Кулинский В.И., Колесниченко Л.С. Структура, свойства, биологическая роль и регуляция глутатионпероксидазы // Успехи современной биологии. – 1993. – Т. 113. – С. 107–122. [Kulinskij VI, Kolesnichenko LS. Struktura, svojstva, biologicheskaja rol’ i reguljatsija glutationperoksidazy. Uspekhi sovremennoj biologii. 1993;113:107-122. (In Russ.)]
  • Alam SK, Konno T, Dai G, et al. A uterine decidual cell cytokine ensures pregnancy-dependent adaptations to a physiological stressor. Development. 2007;134(2):407-415. doi: 10.1242/dev.02743.
  • Разыграев А.В. Определение тиолпероксидазной активности в сыворотке крови крыс с использованием трет-бутилгидропероксида и гомоцистеина // Бутлеровские сообщения. – 2016. – Т. 47. – № 9. – С. 156–162. [Razygraev AV. Determination of thiol peroxidase activity in the rat blood serum using tert-butyl hydroperoxide and homocysteine. Butlerov Communications. 2016;47(9):156-162. (In Russ.)]
  • Разыграев А.В. Опыт использования цистеина для определения тиолпероксидазной активности в плазме и сыворотке крови // Фундаментальная наука и клиническая медицина. Человек и его здоровье: тезисы XVIII Всероссийской медико-биологической конференции молодых исследователей (с международным участием). – СПб., 2015. – С. 449–450. [Razygraev AV. Opyt ispol’zovanija tsisteina dlja opredelenija tiolperoksidaznoj aktivnosti v plazme i syvorotke krovi. Fundamental’naja nauka i klinicheskaja meditsina. Chelovek i ego zdorov’e: tezisy XVIII Vserossijskoj mediko-biologicheskoj konferentsii molodyh issledovatelej (conference proceedings). Saint Petersburg; 2015. P. 449-50. (In Russ.)]
  • Razygraev AV. Cysteine peroxidase activity in rat blood plasma. Egyptian Journal of Biology. 2013;15:54-58. doi: 10.4314/ejb.v15i1.8.


Abstract - 276

PDF (Russian) - 121


Copyright (c) 2017 Razygraev A.V., Matrosova M.O., Titovich I.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.