Genetic aspects of the pathogenesis of missed abortion: the role of vitamin D and its receptors (literature review)
AbstractIn the structure of early reproductive losses missed abortion (MA) occupies a leading position. Prevention of repeated reproductive losses in patients with MA remains one of the priority and complex areas of work of an obstetrician-gynecologist due to the high prevalence of MA in practice and the difference in approaches to its statistical accounting. Promising approaches to solving this problem are the impact on controlled risk factors for MA or its relapses, which are subject to correction at the stage of preconception, as well as the development of methods for predicting the probable risk of repeated MA, including based on the genetic characteristics of the individual. These include the serum level of vitamin D (25-OH) and the genetic aspects of its metabolism.
Keywords:gene polymorphism, vitamin D, vitamin D receptor (VDR) molecular genetic markers, missed abortion
Funding. The authors received no financial support.
Conflict of interest. The authors declare no conflict of interest.
For citation: Ramazanova F.U., Khamoshina M.B., Azova M.M., Mahuop A.A.A., Artemenko Yu.S. Genetic aspects of the pathogenesis of missed abortion: the role of vitamin D and its receptors (literature review). Akusherstvo i ginekologiya: novosti, mneniya, obuchenie [Obstetrics and Gynecology: News, Opinions, Training].2021; 9 (3): 39-45. DOI: https://doi.org/10.33029/2303-9698-2021-9-3-39-45 (in Russian)
References
1. Zhi Z., Yang W., Liu L., et al. Early missed abortion is associated with villous angiogenesis via the HIF-1a/VEGF signaling pathway. Arch Gynecol Obstet. 2018; 298 (3): 537-43. DOI: https://doi.org/10.1007/s00404-018-4802-9
2. Fang J., Xie B., Chen B., et al. Biochemical clinical factors associated with missed abortion independent of maternal age. Medicine. 2018; 97 (50): e13573. DOI: https://doi.org/10.1097/md.00000000000 13573
3. Memtsa M., Jauniaux E., Gulbis B., et al. Maternal serum markers in predicting successful outcome in expectant management of missed miscarriage. Reprod Biomed Online. 2017; 34 (1): 98-103. DOI: https://doi.org/10.1016/j.rbmo.2016.09.004
4. Chen H., Deng X., Yang Y., et al. Expression of GRIM-19 in missed abortion and possible pathogenesis. Fertil Steril. 2015; 103 (1): 138-46. e3. DOI: https://doi.org/10.1016/j.fertnstert.2014.10.012
5. Sharif K., Sharif Y., Watad A., et al. Vitamin D, autoimmunity and recurrent pregnancy loss: more than an association. Am J Reprod Immunol. 2018; 80 (3): e12991. DOI: https://doi.org/10.1111/aji.12991
6. En'kova E.V., Atyakshin D.A., Gayskaya O.V., et al. Evaluation of the population of the mast cells of the decidual tissue and the status of vitamin d in women with undeveloped pregnancy in the embryonic period. Vestnik novykh meditsinskikh tekhnologiy [Bulletin of New Medical Technologies]. 2018; 25 (3): 21-7. (in Russian)
7. Clinical guidelines. Miscarriage in early pregnancy: diagnosis and tactics reference. Rossiyskoe obshhestvo akusherov-ginekologov, 2016. (in Russian)
8. Brown S. Miscarriage and its associations. Semin Reprod Med. 2008; 26 (5): 391-400.
9. Li L., Donghong L., Shuguang W., Hongbo Z., et al. Polymorphisms in the vascular endothelial growth factor gene associated with recurrent spontaneous miscarriage. J Matern Fetal Neonatal Med. 2013; 26 (7): 686-90. DOI: https://doi.org/10.3109/14767058.2012.746305
10. Dicke. G.B. Medical Abortion: A Guide for Practitioners. In: V.E. Radzinsky (ed.). Moscow: MEDpress-inform, 2015: 344 p. ISBN 978-500030-205-7 (in Russian)
11. Andersen L.B., Dechend R., Karumanchi S.A., et al. Early pregnancy angiogenic markers and spontaneous abortion: an Odense Child Cohort study. Am J Obstet Gynecol. 2016; 215 (5): 594.e1-11. DOI: https://doi.org/10.1016/j.ajog.2016.06.007
12. Larsen E.C., Christiansen O.B., Kolte A.M., Macklon N. New insights into mechanisms behind miscarriage. BMC Med. 2013; 11: 154.
13. Lidegaard O., Mikkelsen A., Egerup P., et al. Pregnancy loss. A 40-year nationwide assessment. Acta Obstet Gynecol Scand. 2020; 99 (11): 1492-6. DOI: https://doi.org/10.1111/aogs.13860
14. Carp H.J.A.. Habitual Miscarriage. Causes. Versions and Contra-verses. Treatment. In: V.E. Radzinsky (ed.). Moscow: GEOTAR-Media, 2017: 592 p. (in Russian)
15. Undeveloped Pregnancy. Methodological Recommendations of MARS (Interdisciplinary Association of Specialists in Reproductive Medicine). In: V.E. Radzinsky, et al. (author.-comp.) Moscow : StatusPraesens. 2015: 48 p. (in Russian)
16. Kajdaniuk D., Marek B., Borgiel-Marek H., Kos-Kudta B. Vascular endothelial growth factor (VEGF) in physiology and pathophysiology. Pol J Endocrinol. 2011; 62 (5): 444-55.
17. Su M.T., Lin S.H., Chen Y.C. Genetic association studies of angiogenesis- and vasoconstriction-related genes in women with recurrent pregnancy loss: a systematic review and meta-analysis. Hum Reprod Update. 2011; 17 (6): 803-12. DOI: https://doi.org/10.1093/humupd/dmr027
18. Vidyadhari M., Sujatha M., Krupa P., et al. Association of genetic polymorphism of vascular endothelial growth factor in the etiology of recurrent pregnancy loss: a triad study. J Assist Reprod Genet. 2019; 36 (5): 979-88. DOI: https://doi.org/10.1007/s10815-019-01431-y
19. Sun Y., Chen M., Mao B., et al. Association between vascular endothelial growth factor polymorphism and recurrent pregnancy loss: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2017; 211: 169-76. DOI: https://doi.org/10.1016/j.ejogrb.2017.03.003
20. Keshavarzi F., Shahrakipoor M., Teimoori B., et al. Association of the placental VEGF promoter polymorphisms and VEGF mRNA expression with preeclampsia. Clin Exp Hypertens. 2018; 41 (3): 274-9. DOI: https://doi.org/10.1080/10641963.2018.1469644
21. Ali L.E., Salih M.M., Elhassan E.M., et al. Placental growth factor, vascular endothelial growth factor, and hypoxia-inducible factor-1a in the placentas of women with pre-eclampsia. J Matern Fetal Neonatal Med. 2019; 32 (16): 2628-32. DOI: https://doi.org/10.1080/14767058.2018.1443066
22. Nagy B., Savli H., Molvarec A., et al. Vascular endothelial growth factor (VEGF) polymorphisms in HELLP syndrome patients determined by quantitative real-time PCR and melting curve analyses. Clin Chim Acta. 2008; 389 (1-2): 126-31. DOI: https://doi.org/10.1016/j.cca.2007.12.003
23. Luo L., Chen Y., Wang L., et al. Polymorphisms of genes involved in the folate metabolic pathway impact the occurrence of unexplained recurrent pregnancy loss. Reprod Sci. 2015; 22 (7): 845-51. DOI: https://doi.org/10.1177/1933719114565033
24. Al-Achkar W., Wafa A., Ammar S., et al. Association of methy-lenetetrahydrofolate reductase C677T and A1298C gene polymorphisms with recurrent pregnancy loss in Syrian women. Reprod Sci. 2017; 24 (9): 1275-9. DOI: https://doi.org/10.1177/1933719116682874
25. Kim J.H., Jeon Y.J., Lee B.E., et al. Association of methionine synthase and thymidylate synthase genetic polymorphisms with idiopathic recurrent pregnancy loss. Fertil Steril. 2013; 99 (6): 1674-80. DOI: https://doi.org/10.1016/j.fertnstert.2013.01.108
26. Uitterlinden A.G., Fang Y., Van Meurs J.B., et al. Genetics and biology of vitamin D receptor polymorphisms. Gene. 2004; 338 (2); 143-56. DOI: https://doi.org/10.1016/j.gene.2004.05.014
27. Marozik P.M., Tamulaitiene M., Rudenka E., et al. Association of vitamin D receptor gene variation with osteoporosis risk in Belarusian and Lithuanian postmenopausal women. Front Endocrinol (Lausanne). 2018; 9: 305. DOI: https://doi.org/10.3389/fendo.2018.00305
28. Pezeshki S.M.S., Asnafi A.A., Khosravi A., et al. Vitamin D and its receptor polymorphisms: new possible prognostic biomarkers in leukemias. Oncol Rev. 2018; 12 (2): 366. DOI: https://doi.org/10.4081/oncol.2018.366
29. Zhang D., Wang L., Zhang R., et al. Association of vitamin D receptor gene polymorphisms and the risk of multiple sclerosis - a meta-analysis. Arch Med Res. 2019; 50 (6): 350-61. DOI: https://doi.org/10.1016/j.arcmed.2019.10.007
30. Lee Y.H., Bae S.C., Choi S.J., et al. Associations between vitamin D receptor polymorphisms and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis. Mol Biol Rep. 2011; 38 (6): 3643-51. DOI: https://doi.org/10.1007/s11033-010-0477-4
31. Cusato J., Boglione L., De Nicolo A., et al. Vitamin D pathway gene polymorphisms as predictors of hepatitis C virus-related mixed cryoglobulinemia. Pharmacogenet Genom. 2016; 26 (6): 307-10. DOI: https://doi.org/10.1097/FPC.0000000000000223
32. Wang Q., Xi B., Reilly K. H., et al. Quantitative assessment of the associations between four polymorphisms (FokI, ApaI, BsmI, TaqI) of vitamin D receptor gene and risk of diabetes mellitus. Mol Biol Rep. 2012; 39 (10): 9405-14. DO: https://doi.org/10.1007/s11033-012-1805-7
33. Swapna N., Vamsi U.M., Usha G., et al. Risk conferred by FokI polymorphism of vitamin D receptor (VDR) gene for essential hypertension. Indian J Hum Genet. 2011; 7 (3): 201-6. DOI: https://doi.org/10.4103/0971-6866.92104
34. Reis G.V., Gontijo N.A., Rodrigues K.F., et al. Vitamin D receptor polymorphisms and the polycystic ovary syndrome: a systematic review. J Obstet Gynaecol Res. 2017; 43 (3): 436-46. DOI: https://doi.org/10.1111/jog.13250
35. Shahbazi M., Jeddi-Tehrani M., Zareie M., et al. Expression profiling of vitamin D receptor in placenta, decidua and ovary of pregnant mice. Placenta. 2011; 32 (9): 657-64. DOI: https://doi.org/10.1016/j.placenta.2011.06.013
36. Pospechova K., Rozehnal V., Stejskalova L., et al. Expression and activity of vitamin D receptor in the human placenta and in choriocarcinoma BeWo and JEG-3 cell lines. Mol Cell Endocrinol. 2009; 299 (2): 17887. DOI: https://doi.org/10.1016/j.mce.2008
37. Barrera D., Avila E., Hernandez G., et al. Calcitriol affects hCG gene transcription in cultured human syncytiotrophoblasts. Reprod Biol Endocrinol. 2008; 6: 3. DOI: https://doi.org/10.1186/1477-7827-6-3
38. Guo J., Liu S., Wang P., et al. Characterization of VDR and CYP27B1 expression in the endometrium during the menstrual cycle before embryo transfer: implications for endometrial receptivity. Reprod Biol Endocrinol. 2020; 18 (1): 24. DOI: https://doi.org/10.1186/s12958-020-00579-y
39. Grzesiak M., Waszkiewicz E., Wojtas M., et al. Expression of vitamin D receptor in the porcine uterus and effect of 1,25(OH)2D3 on progesterone and estradiol-17beta secretion by uterine tissues in vitro. Therio-genology. 2019; 125: 102-8.
40. Jang H., Choi Y., Yoo I., et al. Vitamin D-metabolic enzymes and related molecules: expression at the maternal-conceptus interface and the role of vitamin D in endometrial gene expression in pigs. PLoS One. 2017; 12 (10): e0187221. DOI: https://doi.org/10.1371/journal.pone.0187221
41. Liu N.Q., Kaplan A.T., Lagishetty V., et al. Vitamin d and the regulation of placental inflammation. J Immunol. 2011; 186 (10): 5968-74. DOI: https://doi.org/10.4049/jimmunol.1003332
42. Evans K.N., Nguyen L., Chan J., et al. Effects of 25-hydroxyvitamin d3 and 1,25-dihydroxyvitamin d3 on cytokine production by human decidual cells. Biol Reprod. 2006; 75 (6): 816-22. DOI: https://doi.org/10.1095/biolreprod.106.054056
43. Radzinsky V.E., Khamoshina M.B., Tulupova M.S., et al. Proges-teron: disputable issues of therapy and prevention of prematurity and preterm birth. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie [Obstetrics and Gynecology: News, Opinions, Training]. 2019; 7 (3 suppl): 74 - 82. DOI: https://doi.org/10.24411/2303-9698-2019-13910 (in Russian)
44. Barisic A., Pereza N., Hodzic A., et al. Genetic variation in the maternal vitamin D receptor FokI gene as a risk factor for recurrent pregnancy loss. J Matern Fetal Neonatal Med. 2021; 34 (14): 2221-6. DOI: https://doi.org/10.1080/14767058.2019.1660768
45. Baca K.M., Govil M., Zmuda J. M., et al. Vitamin D metabolic loci and vitamin D status in Black and White pregnant women. Eur J Obstet Gynecol Reprod Biol. 2018; 220: 61-8. DOI: https://doi.org/10.1016/j.ejogrb.2017.11.013
46. Hou H., Zhang J.Y., Chen D., et al. Altered decidual and placental catabolism of vitamin D may contribute to the aetiology of spontaneous miscarriage. Placenta. 2020; 92: 1-8. DOI: https://doi.org/10.1016/j.pla-centa.2020.01.013
47. Dutra L.V., Affonso-Kaufman F.A., Cafeo F.R., et al. Association between vitamin D plasma concentrations and VDR gene variants and the risk of premature birth. BMC Pregnancy Childb. 2019; 20 (1): 3. DOI: https://doi.org/10.1186/s12884-019-2671-2
48. Baczynska-Strzecha M., Kalinka J. Influence of apa1 (rs7975232), taq1 (rs731236) and bsm1 (rs154410) polymorphisms of vitamin D receptor on preterm birth risk in the polish population. Ginekol Pol. 2016; 87 (11): 763-8. DOI: https://doi.org/10.5603/GP.2016.0084