The importance of assessing nucleotide polymorphisms of the tp53 signaling pathway genes in uterine infertility factor diagnosis

Abstract

INTRODUCTION: The WHO reported a 30% frequency of female infertility, which does not tend to decrease. Concurrently, the uterine factor occupies one of the most important places in infertility structure, reaching 50%. Improvement of assisted reproductive technology methods can successfully overcome many causes of infertility, but the possibilities of the method are limited in the uterine factor of infertility.

AIM: To assess the presence of nucleotide polymorphisms of the TP53 signaling pathway genes (LIF rs41281637, c.256G>A; LIF rs929271, n.397-2854T>G; MDM2 rs2279744, c.14+309T>G; MDM4 rs1563828, c.558+572A>G; TP53 rs1042522, c.215C>G) in the endometrium in patients with primary and secondary infertility.

MATERIALS AND METHODS: In 2018–2021, the V.F. Snegirev Clinic of Obstetrics and Gynecology examined and treated 54 patients aged 26 to 48 years with primary or secondary infertility, including a genetic endometrial sample examination. The first group consisted of 28 patients with primary infertility aged 26 to 42 years. The 2nd group included 26 patients aged 29 to 48 years with secondary infertility.

RESULTS: The study evaluated the expression of nucleotide polymorphisms of the TP53 signaling pathway genes in patients with primary and secondary infertility. Study results, data were obtained indicating various variants of nucleotide polymorphisms LIF, MDM2, MDM4, and TP53 in primary and secondary infertility, as well as the identity of a marker, such as LIF rs41281637 (G/A) in patients of both groups.

CONCLUSION: The experimental data obtained indicate an important contribution of genetic polymorphisms in the genes of the TP53, LIF and MDM4 signaling pathway to the development of primary and MDM2 — secondary infertility in women.

Keywords

infertility / endometrial receptivity / gene polymorphism

References

[1] Fichman V, Costa RSSD, Miglioli TC, Marinheiro LPF. Association of obesity and anovulatory infertility. Einstein (Sao Paulo). 2020;18:eAO5150. doi: 10.31744/einstein_journal/2020AO5150

[2] Fichman V., Costa R.S.S.D., Miglioli T.C., Marinheiro L.P.F. Association of obesity and anovulatory infertility // Einstein (Sao Paulo). 2020. Vol. 18. P. eAO5150. doi: 10.31744/einstein_journal/2020AO5150

[3] Gambineri A, Laudisio D, Marocco C, et al.; Obesity Programs of nutrition, Education, Research and Assessment (OPERA) group. Female infertility: which role for obesity? Int J Obes Suppl. 2019;9(1):65–72. doi: 10.1038/s41367-019-0009-1

[4] Gambineri A., Laudisio D., Marocco C., et al.; Obesity Programs of nutrition, Education, Research and Assessment (OPERA) group. Female infertility: which role for obesity? // Int J Obes Suppl. 2019. Vol. 9, N 1. P. 65–72. doi: 10.1038/s41367-019-0009-1

[5] Brouillet S, Boursier G, Anav M, et al. C-reactive protein and ART outcomes: a systematic review. Hum Reprod Update. 2020;26(5):753–773. doi: 10.1093/humupd/dmaa012

[6] Brouillet S., Boursier G., Anav M., et al. C-reactive protein and ART outcomes: a systematic review // Hum Reprod Update. 2020. Vol. 26, N 5. P. 753–773. doi: 10.1093/humupd/dmaa012

[7] Tohma YA, Onalan G, Esin S, et al. Are There Any Predictors of Endometrial Premalignancy/Malignancy within Endometrial Polyps in Infertile Patients? Gynecol Obstet Invest. 2019;84(5):512–518. doi: 10.1159/000501682

[8] Tohma Y.A., Onalan G., Esin S., et al. Are There Any Predictors of Endometrial Premalignancy/Malignancy within Endometrial Polyps in Infertile Patients? // Gynecol Obstet Invest. 2019. Vol. 84, N 5. P. 512–518. doi: 10.1159/000501682

[9] Tanos V, Berry KE, Seikkula J, et al. The management of polyps in female reproductive organs. Int J Surg. 2017;43:7–16. doi: 10.1016/j.ijsu.2017.05.012

[10] Tanos V., Berry K.E., Seikkula J., et al. The management of polyps in female reproductive organs // Int J Surg. 2017. Vol. 43. P. 7–16. doi: 10.1016/j.ijsu.2017.05.012

[11] Knyazeva EA, Kuznetsova MV, Shubina ES, et al. Features of methylation of the noha10 and noha11 genes in patients with tubal-peritoneal factor of infertility and unsuccessful attempts of in vitro fertilization in the anamnesis. Obstet Gynecol. 2020;4:140–147. (In Russ). doi: 10.18565/aig.2020.4.140-147

[12] Князева Е.А., Кузнецова М.В., Шубина Е.С., и др. Особенности метилирования генов ноха10 и ноха11 у пациенток с трубно-перитонеальным фактором бесплодия и неудачными попытками экстракорпорального оплодотворения в анамнезе // Акушерство и гинекология. 2020. Т. 4. С. 140–147. doi: 10.18565/aig.2020.4.140-147

[13] Miroshkina MI, Korneeva IE, Burmenskaya OV, Mishina ND. The effectiveness of cryopreservation programs depending on the transcriptional «portrait» of endometrial receptivity genes. Obstet Gynecol. 2020;(11):85–92. (In Russ). doi: 10.18565/aig.2020.11.85-92

[14] Мирошкина М.И., Корнеева И.Е., Бурменская О.В., Мишина Н.Д. Эффективность программ криопереноса в зависимости от транскрипционного «портрета» генов рецептивности эндометрия // Акушерство и гинекология. 2020. № 11. С. 85–92. doi: 10.18565/aig.2020.11.85-92

[15] Hur C, Rehmer J, Flyckt R, Falcone T. Uterine Factor Infertility: A Clinical Review. Clin Obstet Gynecol. 2019;62(2):257–270. doi: 10.1097/GRF.0000000000000448

[16] Hur C., Rehmer J., Flyckt R., Falcone T. Uterine factor infertility: a clinical review // Clin Obstet Gynecol. 2019. Vol. 62, N 2. P. 257–270. doi: 10.1097/GRF.0000000000000448

[17] Turocy JM, Rackow BW. Uterine factor in recurrent pregnancy loss. Semin Perinatol. 2019;43(2):74–79. doi: 10.1053/j.semperi.2018.12.003

[18] Turocy J.M., Rackow B.W. Uterine factor in recurrent pregnancy loss // Semin Perinatol. 2019. Vol. 43, N 2. P. 74–79. doi: 10.1053/j.semperi.2018.12.003

[19] Santos LL, Ling CK, Dimitriadis E. Tripeptidyl peptidase I promotes human endometrial epithelial cell adhesive capacity implying a role in receptivity. Reprod Biol Endocrinol. 2020;18(1):124. doi: 10.1186/s12958-020-00682-0

[20] Santos L.L., Ling C.K., Dimitriadis E. Tripeptidyl peptidase I promotes human endometrial epithelial cell adhesive capacity implying a role in receptivity // Reprod Biol Endocrinol. 2020. Vol. 18, N 1. P. 124. doi: 10.1186/s12958-020-00682-0

[21] Craciunas L, Gallos I, Chu J, et al. Conventional and modern markers of endometrial receptivity: a systematic review and meta-analysis. Hum Reprod Update. 2019;25(2):202–223. doi: 10.1093/humupd/dmy044

[22] Craciunas L., Gallos I., Chu J., et al. Conventional and modern markers of endometrial receptivity: a systematic review and meta-analysis // Hum Reprod Update. 2019. Vol. 25, N 2. P. 202–223. doi: 10.1093/humupd/dmy044

[23] Nag S, Qin J, Srivenugopal KS, Wang M, Zhang R. The MDM2-p53 pathway revisited. J Biomed Res. 2013;27(4):254–271. doi: 10.7555/JBR.27.20130030

[24] Nag S., Qin J., Srivenugopal K.S., Wang M., Zhang R. The MDM2-p53 pathway revisited // J Biomed Res. 2013. Vol. 27, N 4. P. 254–271. doi: 10.7555/JBR.27.20130030

[25] Hu W. The role of p53 gene family in reproduction. Cold Spring Harb Perspect Biol. 2009;1(6):a001073. doi: 10.1101/cshperspect.a001073

[26] Hu W. The role of p53 gene family in reproduction // Cold Spring Harb Perspect Biol. 2009. Vol. 1, N 6. P. a001073. doi: 10.1101/cshperspect.a001073

[27] Bosteels J, van Wessel S, Weyers S, et al. Hysteroscopy for treating subfertility associated with suspected major uterine cavity abnormalities. Cochrane Database Syst Rev. 2018;12(12):CD009461. doi: 10.1002/14651858.CD009461.pub4

[28] Bosteels J., van Wessel S., Weyers S., et al. Hysteroscopy for treating subfertility associated with suspected major uterine cavity abnormalities // Cochrane Database Syst Rev. 2018. Vol. 12, N 12. P. CD009461. doi: 10.1002/14651858.CD009461.pub4

[29] Demirdag E, Guler I, Cevher Akdulum MF, et al. Subsequent IVF outcomes following antibiotic therapy for chronic endometritis in patients with recurrent implantation failure. J Obstet Gynaecol Res. 2021;47(12):4350–4356. doi: 10.1111/jog.15037

[30] Demirdag E., Guler I., Cevher Akdulum M.F., et al. Subsequent IVF outcomes following antibiotic therapy for chronic endometritis in patients with recurrent implantation failure // J Obstet Gynaecol Res. 2021. Vol. 47, N 12. P. 4350–4356. doi: 10.1111/jog.15037

[31] Vagnini LD, Renzi A, Petersen B, et al. Association between estrogen receptor 1 (ESR1) and leukemia inhibitory factor (LIF) polymorphisms can help in the prediction of recurrent implantation failure. Fertil Steril. 2019;111(3):527–534.

[32] Vagnini L.D., Renzi A., Petersen B., et al. Association between estrogen receptor 1 (ESR1) and leukemia inhibitory factor (LIF) polymorphisms can help in the prediction of recurrent implantation failure // Fertil Steril. 2019. Vol. 111, N 3. P. 527–534. doi: 10.1016/j.fertnstert.2018.11.016

[33] doi: 10.1016/j.fertnstert.2018.11.016

[34] Краснопольская К.В., Назаренко Т.А., Ершова И.Ю. Современные подходы к оценке рецептивности эндометрия (обзор литературы) // Проблемы репродукции. 2016. Т. 22, № 5. С. 61–69. doi: 10.17116/repro201622561-69

[35] Krasnopol’skaia KV, Nazarenko TA, Ershova IYu. Modern approaches to endometrial receptivity assessment (a review). Russian Journal of Human Reproduction. 2016;22(5):61–69. (In Russ). doi: 10.17116/repro201622561-69

[36] Гришкина А.А., Чистякова Г.Н., Ремизова И.И., Мелкозерова О.А. Рецептивность эндометрия и экспрессия факторов апоптоза и пролиферации в эндометрии женщин с гиперплазией и бесплодием // Вестник Волгоградского государственного медицинского университета. 2019. № 4 (72). С. 37–39. doi: 10.19163/1994-9480-2019-4(72)-37-39

[37] Grishkina AA, Chistjakova GN, Remizova II, Melkozerova OA. Endometrial receptivity and expression of apoptosis and proliferation factors in the endometrium of women with hyperplasia and infertility. Journal of Volgograd State Medical University. 2019;(4):37–39. (In Russ). doi: 10.19163/1994-9480-2019-4(72)-37-39

[38] Кибанов М.В. Поиск идеального маркера для оценки рецептивности эндометрия: от гистологии до современных молекулярно-генетических подходов // Альманах клинической медицины. 2019. Т. 47, № 1. С. 12–25. doi: 10.18786/2072-0505-2019-47-005

[39] Kibanov MV. The search for the ideal marker for assessing endometrial receptivity: from histology to modern molecular genetic approaches. Almanac of Clinical Medicine. 2019;47(1):12–25. (In Russ). doi: 10.18786/2072-0505-2019-47-005

[40] Парамонова Н.Б., Коган Е.А., Колотовкина А.В., Бурменская О.В. Морфологические и молекулярно-биологические признаки нарушения рецептивности эндометрия при бесплодии женщин, страдающих наружным генитальным эндометриозом // Архив патологии. 2018. Т. 80, № 3. C. 11–18. doi: 10.17116/patol201880311-18

[41] Paramonova NB, Kogan EA, Kolotovkina AV, Burmenskaja OV. Morphological and molecular biological signs of endometrial receptivity disorders in infertility of women suffering from external genital endometriosis. Archive of Pathology. 2018;80(3):11–18. (In Russ). doi: 10.17116/patol201880311-18

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Putilo A.O., Dzhibladze T.A., Pozdnyakova N.V., Grygortsevich N.Y., Svidinskaya E.A., Zuev V.M., Khokhlova I.D.