Influence of heavy metals on the effectiveness of assisted reproductive technologies depending on the polymorphism of genes of the detoxification system


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Aim. To analyze the relationship between the levels of heavy metals (cadmium, mercury, lead) in the blood, polymorphism of genes of the biotransformation system of xenobiotics and the outcomes of assisted reproductive technologies (ART) in infertile women. Materials and methods. 300 married couples underwent infertility treatment using ART. The levels of mercury, cadmium and lead in the blood of patients were detected using inductively coupled plasma mass spectrometry. The allelic variants of genes of the detoxification system were determined by real-time polymerase chain reaction with melting curve analysis. Results. The blood levels of lead and mercury were significantly lower in patients with the absence of T allele of CYP1A1 gene and in patients with G allele of GSTP1 gene. Mercury level was also low in the absence of deletion of GSTT1 gene. The blood level of cadmium was not associated with genes polymorphism of xenobiotic biotransformation. The patients with absent T allele of CYP1A1 gene had low birth rate (р=0.0270), and low cumulative birth rate (р=0.0249): 51.6% in patients with T/Tgenotype, 38.1% in patients with T/C genotype and 20% in patients with С/С genotype. The combined index of CYP1A1*Pb in the blood significantly influenced fertilization of oocytes. Conclusion. The obtained data showed that polymorphic variants of genes of the detoxification system play an important role in the accumulation of heavy metals in the body of patients, as well as in reduced rate of oocyte fertilization in ART cycles.

Full Text

Restricted Access

About the authors

Anastasia G. Syrkasheva

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: a_syrkasheva@oparina4.ru
PhD, Senior Researcher of the IVF Department

Nataliya V. Dolgushina

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: n_dolgushina@oparina4.ru
Dr. Med. Sci., Deputy Director - Head of the Department of Research Administration

Vladimir E. Frankevich

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: v_frankevich@oparina4.ru
PhD, Head of the Department of Systems Biology in Reproduction

Andrey E. Donnikov

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: a_donnikov@oparina4.ru
PhD, Head of the Laboratory of Molecular Genetic Methods

References

  1. Centers for Disease Control and Prevention. Fourth national report on human exposure to enviromental chemicals. Atlanta, GA : U.S. Department of Health and Human Services; 2009.
  2. Tolunay H.E., Şükür Y.E., Ozkavukcu S., Seval M.M., Ateş C., Türksoy V.A. et al. Heavy metal and trace element concentrations in blood and follicular fluid affect ART outcome. Eur. J. Obstet. Gynecol. Reprod. Biol. 2016; 198: 73-7. https://dx.doi.org/10.1016/j.ejogrb.2016.01.001.
  3. Сыркашева А.Г., Франкевич В.Е., Долгушина Н.В. Ассоциация между уровнем тяжелых металлов в организме женщин с бесплодием и исходами программ вспомогательных репродуктивных технологий. Акушерство и гинекология. 2020; 11: 124-30. [Syrkasheva A.G., Frankevich V.E., Dolgushina N.V. Association between heavy metals in infertile women and IVF outcomes. Akusherstvo i ginekologia/Obstetrics and Gynecology. 2020; 11: 124-30 (in Russian)]. https://dx.doi.org/10.18565/aig.2020.11.124-130.
  4. Казанцева Е.В., Долгушина Н.В.,Донников А.Е., Беднягин Л.А., Баранова Е.Е., Терешков П.П. Влияние пренатальной экспозиции бенз(а)пирена, стирола и формальдегида на массу тела при рождении в зависимости от полиморфизмов генов системы детоксикации. Акушерство и гинекология. 2016; 7: 68-78. https://dx.doi.org/10.18565/aig.2016.7.68-78.
  5. Долгушина Н.В., Казанцева Е.В., Пивоварова Л.В. Влияние антропогенных химических веществ на массу тела новорожденных. Акушерство и гинекология. 2013; 12: 58-64.
  6. Сыркашева А.Г., Долгушина Н.В., Макарова Н.П., Ковальская Е.В., Агаршева М.А. Исходы программ вспомогательных репродуктивных технологий у пациенток с дисморфизмами ооцитов. Акушерство и гинекология. 2015; 7: 56-62.
  7. Rzymski P., Rzymski P., Tomczyk K., Niedzielski P., Jakubowski K., Poniedzialek B. et al. Metal status in human endometrium: relation to cigarette smoking and histological lesions. Environ. Res. 2014; 132: 328-33. https://dx.doi.org/10.1016/j.envres.2014.04.025.
  8. Pizzol D., Foresta C., Garolla A., Demurtas J., Trott M., Bertoldo A. et al. Pollutants and sperm quality: a systematic review and meta-analysis. Environ. Sci. Pollut. Res. Int. 2021; 28(4): 4095-103. https://dx.doi.org/10.1007/s11356-020-11589-z.
  9. Carvalho L.V.B., Hacon S.S., Vega C.M., Vieira J.A., Larentis A.L., Mattos R.C.O.C. et al. Oxidative stress levels induced by mercury exposure in Amazon Juvenile Populations in Brazil. Int. J. Environ. Res. Public Health. 2019; 16(15): 2682. https://dx.doi.ojs/10.3390/ijerph16152682.
  10. Lee S., Min J. Y., Min K.B. Female infertility associated with blood lead and cadmium levels. Int. J. Environ. Res. Public Health. 2020; 17(5): 1794. https://dx.doi.org/10.3390/ijerph17051794.
  11. Lamichhane D.K., Leem J.H., Park C.S., Ha M., Ha E.H., Kim H.C. et al. Associations between prenatal lead exposure and birth outcomes: Modification by sex and GSTM1/GSTT1 polymorphism. Sci. Total Environ. 2018; 619-620: 176-84
  12. Shojaeepour S., Fazeli M., Oghabian Z., Pourgholi L., Mandegary A. Oxidative stress in opium users after using lead-adulterated opium: The role of genetic polymorphism. Food Chem. Toxicol. 2018; 120: 571-7. https://dx.doi.org/10.1016/j.fct.2018.07.061
  13. Su H., Cao Y., Li J., Zhu Y., Ma X. GST null polymorphisms may affect the risk of coronary artery disease: evidence from a meta-analysis. Thromb. J. 2020; 18: 20. https://dx.doi.org/10.1186/s12959-020-00234-x
  14. Chatterjee A., Gupta S. The multifaceted role of glutathione S-transferases in cancer. Cancer Lett. 2018; 433: 33-42. https://dx.doi.org/10.1016/j.canlet.2018.06.028.
  15. Bowatte G., Lodge C.J., Perret J.L., Matheson M.C., Dharmage S.C. Interactions of GST polymorphisms in air pollution exposure and respiratory diseases and allergies. Curr. Allergy Asthma Rep. 2016; 16(12): 85. 1 https://dx.doi.org/0.1007/s11882-016-0664-z.
  16. Broekman M.M.T.J., Bos C., Te Morsche R.H.M., Hoentjen F., Roelofs H.M.J., Peters W.H.M. et al. GST Theta null genotype is associated with an increased risk for ulcerative colitis: a case-control study and meta-analysis of GST Mu and GST Theta polymorphisms in inflammatory bowel disease. J. Hum. Genet. 2014; 59(10): 575-80. https://dx.doi.org/10.1038/jhg.2014.77.
  17. Du Y., Zhang H., Xu Y., Ding Y., Chen X., Mei Z. et al. Association among genetic polymorphisms of GSTP1, HO-1, and SOD-3 and chronic obstructive pulmonary disease susceptibility. Int. J. Chron. Obstruct. Pulmon. Dis. 2019; 14: 2081-8. https://dx.doi.org/10.2147/COPD.S213364.
  18. Nishikawa T., Yamaguchi H., Ikawa K., Nakayama K., Higashi E., Miyahara E. et al. Influence of GST polymorphisms on busulfan pharmacokinetics in Japanese children. Pediatr. Int. 2019; 61(6): 558-65. https://dx.doi.org/10.1111/ped.13859.
  19. Hussein A.G., Pasha H.F., El-Shahat H.M., Gad D.M., Toam M.M. CYP1A1 gene polymorphisms and smoking status as modifier factors for lung cancer risk. Gene. 2014; 541(1): 26-30. https://dx.doi.org/10.1016/j.gene.2014.03.003.
  20. Hidaka A., Sasazuki S., Matsuo K., Ito H., Charvat H., Sawada N. et al. CYP1A1, GSTM1 and GSTT1 genetic polymorphisms and gastric cancer risk among Japanese: A nested case-control study within a large-scale population-based prospective study. Int. J. Cancer. 2016; 139(4): 759-68. https://dx.doi.org/10.1002/ijc.30130.
  21. Wongpratate M., Ishida W., Phuthong S., Natphopsuk S., Ishida T. Genetic polymorphisms of the human cytochrome P450 1A1 (CYP1A1) and cervical cancer susceptibility among Northeast Thai women. Asian Pac. J. Cancer Prev. 2020; 21(1): 243-8. https://dx.doi.org/10.31557/APJCP.2020.21.L243.

Supplementary files

Supplementary Files
Action
1. JATS XML

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies