POLYMORPHISM OF SOME GENES IN PATIENTS WITH CHRONIC ENDOMETRITIS

Abstract

Chronic inflammation of the endometrium is one of the causes of infertility and impaired menstrual function. The issues of the diagnosis and treatment of this disease are often discussed, but remains too unclear. In connection with this, the study of the role of genetic polymorphism in patients with chronic endometritis is topical. The occurrence of polymorphisms in promoter sites of VEGF, ApoE, ESR1, PPARGC1A, MMP9, eNOS genes in patients with chronic endometritis and in practically healthy women were studied. As primers, the DNA portion of the VEGF genes rs2010963 (G634C), ApoE rs429358 (Cys130Arg), ESR1 2228480 (Thr594Thr), PPARGC1A 8192678 (Gly482Ser), MMP9 17576 (Gln279Arg), and eNOS 1799983 (Glu298Asp) were used. To study the polymorphic variants of genes investigated, a real-time polymerase chain reaction was used, the material was sampled by smear extraction from the mucous membrane of the oropharynx. In the analysis, the percentage of homozygotes and heterozygotes, the prevalence of the normal and pathological (minor) allele were counted. Based on the results obtained, it can be assumed that in patients with chronic endometritis polymorphism of genes responsible for angiogenesis, oxidative processes in the body and metabolism is more common. In particular, there was noted a statistically significant predominance of polymorphism in the promoter sites of the eNOS and ESR1 genes in patients with chronic endometritis, which may be indicative of negative genetic associations with impaired fertility; at the same time, the issues of the presence of genetic polymorphism of the genes MMP9, VEGF and ApoE and a lower frequency of somatic and gynecological pathology in a group of practically healthy women require further study.

Keywords

chronic endometritis / gene polymorphism / somatic pathology / practically healthy women

References

[1] Noyes R.W., Hertig A.T., Rock J. Dating the endometrial biopsy. Fertil. and Steril. 1950; 1: 3-25.

[2] Diedrich K., Fauser B.C., Devroey P., Griesinger G., Evian Annual Reproduction (EVAR) Workshop Group. The role of the endometrium and embryo in human implantation. Hum. Reprod. Update. 2007; 13(4): 365-77.

[3] Talbi S., Hamilton A.E., Vo K.C., Tulac S., Overgaard M.T., Dosiou C. et al. Molecular phenotyping of human endometrium distinguishes menstrual cycle phases and underlying biological processes in normo-ovulatory women. Endocrinology. 2006; 147: 1097-121.

[4] Ponnampalam A.P., Weston G.C., Trajstman A.C., Susil B., Rogers P.A. Molecular classification of human endometrial cycle stages by transcriptional profiling. Mol. Hum. Reprod. 2004; 10: 879-93.

[5] Sharkey A.M., Smith S.K. The endometrium as a cause of implantation failure. Best Pract. Res. Clin. Obstet. Gynaecol. 2003; 17: 289-307.

[6] Coutifaris C., Myers E.R., Guzick D.S., Diamond M.P., Carson S.A., Legro R.S. et al. NICHD National Cooperative Reproductive Medicine Network, Histological dating of timed endometrial biopsy tissue is not related to fertility status. Fertil. and Steril. 2004; 82: 1264-72.

[7] Lessey B.A. Assessment of endometrial receptivity. Fertil. and Steril. 2011; 96:522-9.

[8] Aghajanova L., Hamilton A.E., Giudice L.C. Uterine receptivity to human embryonic implantation: histology, biomarkers, and transcriptomics. Semin. Cell Dev. Biol. 2008; 19: 204-11.

[9] Haouzi D., Dechaud H., Assou S., De Vos J., Hamamah S. Insights into human endometrial receptivity from transcriptomic and proteomic data. Reprod. Biomed. Online. 2011; http://dx.doi.org/10.1016/j.rbmo.2011.09.009.

[10] Martin J., Dominguez F., Avila S., Castrillo J.L., Remohi J., Pellicer A., Simon C. Human endometrial receptivity: gene regulation. J. Reprod. Immunol. 2002; (55): 131-9.

[11] Margalioth E.J., Ben-Chetrit A., Gal M., Eldar-Geva T. Investigation and treatment of repeated implantation failure following IVF-ET. Hum. Reprod. 2006; 21: 3036-43.

[12] Bersinger N.A., Wunder D.M., Birkhauser M.H., Mueller M.D. Gene expression in cultured endometrium from women with different outcomes following IVF. Mol. Hum. Reprod. 2008; 14: 475-84.

[13] Kao L.C., Germeyer A., Tulac S., Lobo S., Yang J.P., Taylor R.N. et al. Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure andinfertility. Endocrinology. 2003; 144: 2870-81.

[14] Hynes R.O. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992; 69: 11-25.

[15] Lessey B.A., Damjanovich L., Coutifaris C., Castelbaum A., Albelda S.M., Buck C.A. Integrin adhesion molecules in the human endometrium. Correlationwith the normal and abnormal menstrual cycle. J. Clin. Invest. 1992; 90: 188-95.

[16] Meseguer M., Aplin J.D., Caballero-Campo P., O’Connor J.E., Martin J.C., Remohi J. et al. Human endometrial mucin MUC1 is up-regulated by progesterone and down-regulated in vitro by the human blastocyst. Biol. Reprod. 2001; 64: 590-601.

[17] Tabibzadeh S., Sun X.Z. Cytokine expression in human endometrium throughout the menstrual cycle. Hum. Reprod. 1992; 7: 1214-21.

[18] Henriquez S., Tapia A., Quezada M., Vargas M., Cardenas H., Rios M. et al. Deficient expression of monoamine oxidase A in the endometriumis associated with implantation failure in women participating as recipients inoocyte donation. Mol. Hum. Reprod. 2006; 12: 749-54.

[19] Lee J., Oh J., Choi E., Park I., Han C., Kim do H., Choi B.C., Kim J.W., Cho C. Differentially expressed genes implicated in unexplained recurrent spontaneous abortion. Int. J. Biochem. Cell Biol. 2007; 39: 2265-77.

[20] Carson D.D., Lagow E., Thathiah A., Al-Shami R., Farach-Carson M.C., Vernon M. et al. Changes in gene expression during the early tomid-luteal (receptive phase) transition in human endometrium detected by high-density microarray screening. Mol. Hum. Reprod. 2002; 8: 871-9.

[21] Kao L.C., Tulac S., Lobo S., Imani B., Yang J.P., Germeyer A. et al. Global gene profiling in human endometrium during the window of implantation. Endocrinology. 2002; 143: 2119-38.

[22] Borthwick J.M., Charnock-Jones D.S., Tom B.D., Hull M.L., Teirney R., Phillips S.C, Smith S.K. Determination of the transcript profile of human endometrium. Mol. Hum. Reprod. 2003; 9: 19-33.

[23] Riesewijk A., Martin J., van Os R., Horcajadas J.A., Polman J., Pellicer A. Gene expression profiling of human endometrial receptivityon days LH+2 versus LH+7 by microarray technology. Mol. Hum. Reprod. 2003; 9: 253-64.

[24] Mirkin S., Arslan M., Churikov D., Corica A., Diaz J.I., Williams S. et al. In search of candidate genes critically expressed in the human endometrium during the window of implantation. Hum. Reprod. 2005; 20: 2104-17.

[25] Horcajadas J.A., Pellicer A., Simon C. Wide genomic analysis of human endometrial receptivity: new times, new opportunities. Hum. Reprod. Update. 2007; 13: 77-86.

[26] Diaz-Gimeno P., Horcajadas J.A., Martinez-Conejero J.A., Esteban F.J., Alama P., Pellicer A., Simon C. A genomic diagnostic tool for human endometrial receptivity based on the transcriptomic signature. Fertil. and Steril. 2011; 95: 50-60 (60.e1-15).

[27] Bagheri A., Kumar P., Kamath A., Rao P. Association of angiogenic cytokines (VEGF-A and VEGF-C) and clinical characteristic in women with unexplained recurrent miscarriage. Bratisl. Lek. Listy. 2017; 118(5): 258-64.

[28] Mirzaei K., Hossein-Nezhad A., Emamgholipour S., Ansar H., Khosrofar M., Tootee A., Alatab S. An exonic peroxisome proliferator-activated receptor-g coactivator-16 variation may mediate the resting energy expenditure through a potential regulatory role on important gene expression in this pathway. J. Nutrigenet. Nutrigenomics. 2012; 5(2): 59-71.

[29] Ignarro L.J. Biosynthesis and methabolism of endothelium-derived nitric oxide. Pharmacol. Toxicol. 1990; 67: 1-7.

[30] Шевченко А.В., Коненков В.И., Прокофьев В.Ф., Покушалов Е.А. Анализ комбинаций генотипов в полиморфных точках промоторных участков генов трёх матричных металлопротеиназ (ММР) и гена фактора роста эндотелия сосудов (VEGF) у пациентов, перенёсших острый инфаркт миокарда. Терапевтический архив. 2014; 86(4): 19-24

[31] Corbo R.M., Ulizzi L., Piombo L., Scacchi R. Study on a possible effect of four longevity candidate genes (ACE, PON1, PPAR-gamma, and APOE) on human fertility. Biogerontology. 2008; 9(5): 317-23.

[32] Paskulin D.D., Cunha-Filho J.S., Paskulin L.D., Souza C.A.B., Ashton-Prolla P. ESR1 rs9340799 is associated with endometriosis-related infertility and in vitro fertilization failure. Disease Markers. 2013; 35(6): 907-13.

[33] Перечень маркеров генного полиморфизма, отвечающих за особенности мутагенной активности техногенных химических факторов. Методические рекомендации МР 4.2.0075-13 от 20.08.2013. Зайцева Н.В., Долгих О.В., Кривцов А.В., Дианова Д.Г., Ланин Д.В., Лыхина Т.С. и др., ФБУН «Федеральный научный центр медико-профилактических технологий управления рисками здоровью населения» Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека; Богун А.Г., ФБУН «Государственный научный центр прикладной микробиологии и биотехнологии». М.; 2013

RIGHTS & PERMISSIONS

Eco-Vector