Volume 6, Issue 4, July 2018, Page: 71-79
Genetic and Epigenetic Mechanisms of Endometral Reciptivity Disorder in Patients Born with Low Weight
Melkozerova Oxana Alexandrovna, Department Reproductive Functions Preservation, Ural Research Institute of Maternity and Child Care, Ekaterinburg, Russia
Bashmakova Nadezda Vasilyevna, Scientific Administration, Ural Research Institute of Maternity and Child Care, Ekaterinburg, Russia
Tretyakova Tatyana Borisovna, Genetics Laboratory, Ural Research Institute of Maternity and Child Care, Ekaterinburg, Russia
Schedrina Irina Dmitrievna, Department Reproductive Functions Preservation, Ural Research Institute of Maternity and Child Care, Ekaterinburg, Russia
Received: Jun. 5, 2018;       Accepted: Jul. 12, 2018;       Published: Aug. 7, 2018
DOI: 10.11648/j.jgo.20180604.11      View  485      Downloads  35
Abstract
The aim is to study genetic and intrauterine epigenetic mechanisms of endometrial receptivity disorders in patients with reproductive failures. 96 girls of adolescents with disturbed menstrual function as anomalous uterine bleeding (AUB PP) and 210 women of reproductive age, suffering from uterine infertility or miscarriage, due to "thin" endometrium were examined. All the patients were born on the deadline. Within the main cohorts, the patients were stratified according to their birth weight. Clinical anamnestic data and molecular genetic studies of polymorphic variants of sex steroids receptor genes, endothelial function regulation genes, angiogenesis and thrombophilia were analyzed using the "real-time" allele-specific polymerase chain reaction with melting curves of the amplification products using a set of reagents and protocols of the company Test Gen LTD (Russia). The risk of reproductive failures due to impaired receptivity of the endometrium is associated with the carrier of the polymorphic allele A of the VEGF2578C gene> A: for patients with infertility (OR = 2.73 (1.36-5.45), p = 0.01) and miscarriage OR = 4.61 (2.19-9.71), p = 0.01) and bearing the polymorphic allele 675 4G of the PAI-1 gene 675 5G> 4G: for patients with infertility (OR = 8.45 (3, 96-18,21), p = 0,001) and miscarriage (OR = 9.98 (4.61-21.74), p = 0.001). The carrier of polymorphism pVull-СС of the gene ESR1 397T> C is associated with an increased risk of disruption of the development of the menstrual function, manifested by abnormal uterine bleeding of the pubertal period (OR = 4.58 (0.97-21.68) p = 0.04), and the risk of developing in the reproductive age of miscarriage, caused by a "thin" endometrium (OR = 6.79 (1.94-23.75), p = 0.01). In women born with low weight, a significantly higher frequency of genotypes containing polymorphic allele 786C of the gene for endothelial NO-synthase NOS3 786 T> C was determined: for women with infertility OR = 6.173 (1.83-20.83); p = 0.001; for women with miscarriage OR = 4.902 (1.69-14.08); p = 0.002; for girls OR = 2.56 (1.01-6.50); p = 0.04. The genetic network containing the described variable alleles coordinates the pathological nature of the regulation of the endometrial function, which can lead to the formation of a "thin" non-receptive endometrium in response to traumatic injury.
Keywords
Endometrial Receptivity, "Thin" Endometrium, Genetic Regulation, Epigenetic Regulation, Low Birth Weight
To cite this article
Melkozerova Oxana Alexandrovna, Bashmakova Nadezda Vasilyevna, Tretyakova Tatyana Borisovna, Schedrina Irina Dmitrievna, Genetic and Epigenetic Mechanisms of Endometral Reciptivity Disorder in Patients Born with Low Weight, Journal of Gynecology and Obstetrics. Vol. 6, No. 4, 2018, pp. 71-79. doi: 10.11648/j.jgo.20180604.11
Copyright
Copyright © 2018 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Reference
[1]
Black R. E. Global Prevalence of Small for Gestational Age. Births. Nestle Nutr. Inst. Workshop. Ser. 2015; 81: 1-7. http://doi:10.1159/000365790
[2]
Lee A. C., Katz J., Blencowe H.. National and regional estimates of the term and preterm of babies born in the low-income and middle-income countries in 2010. Lancet Glob Health. 2013; 1 (2): 26-36. https://doi.org/10.1016/S2214-109X(13)70006-8
[3]
Barker D. J. The origins of the developmental origins theory. J. Intern. Med. 2007; 261 (5): 412-417.
[4]
Chernausek S. D. Update: Consequences of Abnormal Fetal Growth. J. Clin. Endocrinol. Metab. 2012; 97: 689-695. https://doi.org/10.1210/jc.2011-2741
[5]
Voerman E, Jaddoe VW, Franco OH, Steegers EA, Gaillard R. Critical periods and growth patterns from fetal life onwards associated with childhood insulin levels. Diabetologia. 2017; 60(1): 81–88. https://doi.org/10.1007/s00125-016-4135-9
[6]
Christian L. R., Sheela S. Mechanisms of neuroendocrine and epigenetic regulation of body weight and onset of puberty. Rev. Endocr. Metab. Disord. 2012; 13: 129-140.
[7]
Kawai T., Yamada T., Abe K., Okamura K., Kamura Hi., Akaishi R. Increased epigenetic alterations at the promoters of transcriptional regulators following inadequate maternal gestational weight gain. Sci Rep. 2015; 5: 142-224. https://doi.org/10.1038/srep03843
[8]
Baranov AA, Kuchma VR, Namazova L. S. Health and development of adolescents in Russia. M.: NTSZD RAMS; 2010. 102 p.
[9]
Talib HJ. Adolescent Gynecology. Springer; 2018. 23 p.
[10]
Dankova IV, Bashmakova NV, Chistyakova G. N. Peculiarities of puberty flow in adolescent girls born with manifestations of intrauterine growth retardation. Reproductive health of children and adolescents. 2013; 1: 44-52.
[11]
Barker D. J. Intrauterine programming of adult disease. Mol. Med. Today. 1995; 1 (9): 418-423.
[12]
Nasr H. B., Dimassi S., M'hadhbi R. Functional G894T (rs1799983) polymorphism and intron-4 VNTR variant of nitric oxide synthase (NOS3) gene are susceptibility biomarkers of obesity among Tunisians. Obes. Res. Clin. Pract. 2015; 5 (4): 1871-1903. https://doi.org/10.1016/j.orcp.2015.04.008
[13]
Chan Y, Salem RM, Hsu YH, McMahon G, Pers TH, Vedantam S, Esko T, Guo MH, Lim ET et al. Genome-wide Analysis of Body Proportion Classifies Height-Associated Variants by Mechanism of Action and Implicates Genes Important for Skeletal Development. Am J Hum Genet. 2015 May 7; 96(5):695-708. https://doi.org/10.1016/j.ajhg.2015.02.018
[14]
Ali S. M., Khalil R. A. Genetic, Immune, and Vasoactive Factors in the Vascular Dysfunction Associated with Hypertension in Pregnancy. Expert. Opin. Ther. Targets. 2015; 19 (11): 1495-1515. https://doi.org/10.1517/14728222.2015.1067684
[15]
Haram K. Genetic Aspects of Preeclampsia and the HELLP Syndrome. J. Pregnancy. 2014; 9: 107-151.
[16]
Leonardo D. P., Albuquerque D. M., Lanaro C. Association of Nitric Oxide Synthase and Matrix Metalloprotease Single Nucleotide Polymorphisms with Preeclampsia and Its Complications. PLoS One. 2015; 10 (8): 66 - 93. https://doi.org/10.1371/journal.pone.0136693
[17]
Lockwood C. J., Nemerson Y., Guller S. Decidualized Human Endometrial Stromal Cells Mediate Hemostasis, Angiogenesis, and Abnormal Uterine Bleeding. Reprod Sci. Feb. 2009; 16 (2): 62-170. https://doi.org/10.1177/1933719108325758
[18]
Asif A. R., Oellerich M., Armstrong V. W. Polymorphism of the nos-3 Gene and the Endothelial Cell Response to Fluid Shear Stress - A Proteome Analysis. Journal of Proteome Research. 2009; 8 (6): 3161-3168. https://doi.org/10.1021/pr800998k
[19]
Monti L. D., Galluccio E., Fontana B. Pharmacogenetic influence of NOS3 gene variant on endothelial and glucose metabolism responses to L-arginine supplementation: Post hoc analysis of the L-arginine trial. Metabolism. 2015; 64 (11): 1582-1591.
[20]
Sung J. H., Lee B. E., Kim J. O. Association between NOS3 polymorphisms and risk of coronary artery disease in a Korean population: a meta-analysis. Genet. Mol. Res. 2015; 9 (4): 16508-16520. https://doi.org/10.4238/2015
[21]
Ozsoy A. Z., Karakus N. H., Yigit S.G. The Evaluation of IL6 and ESR1 Gene Polymorphisms in Primary Dysmenorrhea. Immunol Invest. 2016; 45: 75-86.
[22]
Shen C., Chen J., Fan S. Association between the polymorphism of estrogen receptor α and coronary artery disease in a Chinese population. European Journal of Internal Medicine. 2012; 23: 175-178. https://doi.org/10.7150/ijms.5234
[23]
Clapauch R., Mourão A. F., Mecenas A. S. Endothelial function and insulin resistance in early postmenopausal women with cardiovascular risk factors: importance of ESR1 and NOS3 polymorphisms. PLoS One. 2014; 9 (7): 34-44. https://doi.org/10.1371/journal.pone.0103444
[24]
Gombolevskaya NA, Burmenskaya OV, Demura TA, Marchenko LA Evaluation of mRNA expression of cytokine genes in endometrium in chronic endometrium. Obstetrics and gynecology. 2013; 11: 35-40.
[25]
Joris V, Gomez EL, Menchi L, Lobysheva I, Di Mauro V, Esfahani H, Condorelli G, Balligand JL, Catalucci D, Dessy C. MicroRNA-199a-3p and MicroRNA-199a-5p Take Part to a Redundant Network of Regulation of the NOS (NO Synthase)/NO Pathway in the Endothelium. Arterioscler Thromb Vasc Biol. 2018; ATVBAHA.118.311145. https://doi.org/10.1161/ATVBAHA.118.311145
[26]
Hou Q, Li MY, Huang WT, Wei FF, Peng JP, Lou MW, Qiu JG. Association between three VEGF polymorphisms and renal cell carcinoma susceptibility: a meta-analysis. Oncotarget. 2017; Jul 25; 8(30):50061-50070. https://doi.org/10.18632/oncotarget.17833
[27]
Prakash S, Agrawal S., Kumar S. Impact of Vascular Endothelial Growth Factor Single Nucleotide Polymorphism Association on Acute Renal Allograft Rejection. Nephron. 2015; 129: 91-96. https://doi.org/10.1159/000368700
[28]
Liu F., Luo L., Wei Y. Association of VEGFA polymorphisms with susceptibility and clinical outcome of hepatocellular carcinoma in a Chinese Han population. Oncotarget. 2017; 8 (10): 16488-16497. https://doi.org/10.18632/oncotarget.14870
[29]
Ye Y, Vattai A, Zhang X, Zhu J, Thaler CJ, Mahner S, Jeschke U, von Schönfeldt V. Role of Plasminogen Activator Inhibitor Type 1 in Pathologies of Female Reproductive Diseases. Int J Mol Sci. 2017; Jul 29; 18(8). https://doi.org/10.3390/ijms18081651
[30]
Li Z. L., Ueki K., Kumagai K. Regulation of bcl-2 transcription by estrogen receptor-alpha and C-Jun in human endometrium. Med. Mol. Morphol. 2014; 47 (1): 43-53.
Browse journals by subject