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Association of functional superoxide gene polymorphism with chlamydia trachomatis-associated recurrent spontaneous abortion

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Abstract

Background

Oxidative stress generated by Chlamydia trachomatis infection is associated with reproductive complications such as recurrent spontaneous abortion. Aim of prospective study was to evaluate whether single nucleotide polymorphisms (SNPs) of SOD1 and SOD2 gene are associated with C. trachomatis-infected recurrent spontaneous abortion (RSA).

Methods

150 patients with history of RSA and 150 patients with history of successful deliveries were recruited from Department of Obstetrics and Gynecology, Safdarjung hospital, New Delhi, India. Urine and non-heparinized blood samples were collected and C. trachomatis was detected by polymerase chain reaction (PCR). Using qualitative real time PCR, SNPs rs4998557 (SOD1) and rs4880 (SOD2) were screened in enrolled patients. Level of 8-hydroxyguanosine (8-OHdG), 8-isoprostane (8-IP), progesterone and estrogen was determined by enzyme-linked immunosorbent assays and correlated with SNPs.

Results

Significant differences were found in frequency of AA genotype of SOD1 gene among RSA patients versus controls, (82% and 54.66%, respectively; p = 0.02; OR 0.40; CI 95%). Frequency of AA genotype of SOD1 gene among RSA patients with C. trachomatis infection was 87.33%, while in uninfected RSA patients was 71.33% (p < 0.0001; OR 8; CI 95%). No significant relation was found between SOD2 (rs4880) genotype and RSA. Furthermore, significant increase in 8-OHdG, 8-IP and estrogen and significant decrease in progesterone was observed among patients carrying AA genotype.

Conclusions

Findings suggest the clinical importance of AA genotype along with 8-OHdG, 8-IP and estrogen and progesterone in screening C. trachomatis-infected RSA women.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Ray A, Bhati T, Arora R, Pradhan D, Parvez S, Rastogi S (2021) Differential expression of urine-circulating micro-RNAs in Chlamydia trachomatis-induced recurrent spontaneous aborters. Microb Pathog 160:105156

    Article  CAS  PubMed  Google Scholar 

  2. Vigil P, Tapia A, Zacharias S, Riquelme R, Salgado AM, Varleta J (2002) First-trimester pregnancy loss and active Chlamydia trachomatis infection: correlation and ultrastructural evidence. Andrologia 34:373–378

    Article  CAS  PubMed  Google Scholar 

  3. Agarwal A, Gupta S, Sharma RK (2005) Role of oxidative stress in female reproduction. Reprod Biol Endocrinol 14:3:28. https://doi.org/10.1186/1477-7827-3-28

    Article  CAS  Google Scholar 

  4. Agarwal A, Aponte-Mellado A, Premkumar BJ, Shaman A, Gupta S (2012) The effects of oxidative stress on female reproduction: a review. Reprod Biol Endocrinol 10:1–31

    Article  Google Scholar 

  5. Agarwal A, Gupta S, Malhotra N, Sharma D (2009) Oxidative stress and its role in female infertility and assisted reproduction: clinical implications. Int J Fertil Steril 2:147–164

    Google Scholar 

  6. Prusty BK, Böhme L, Bergmann B, Siegl C, Krause E, Mehlitz A, Rudel T (2012) Imbalanced oxidative stress causes chlamydial persistence during non-productive human herpes virus co-infection. PLoS One e47427. https://doi.org/10.1371/journal.pone.0047427

    Article  Google Scholar 

  7. Gupta S, Agarwal A, Banerjee J, Alvarez JG (2007) The role of oxidative stress in spontaneous abortion and recurrent pregnancy loss: a systematic review. Obstet Gynecol Surv 62:335–347

    Article  PubMed  Google Scholar 

  8. Lu J, Wang Z, Cao J, Chen Y, Dong Y (2018) A novel and compact review on the role of oxidative stress in female reproduction. Reprod Biol Endocrinol 16:1–8

    Article  Google Scholar 

  9. Duhig K, Chappell LC, Shennan AH (2016) Oxidative stress in pregnancy and reproduction. Obs Med 9:113–116

    Article  Google Scholar 

  10. Polimanti R, Graziano ME, Lazzarin N, Vaquero E, Manfellotto D, Fuciarelli M (2014) GSTO1 uncommon genetic variants are associated with recurrent miscarriage risk. Fertil Steril 101:735–739

    Article  CAS  PubMed  Google Scholar 

  11. Polimanti R, Piacentini S, Lazzarin N, Vaquero E, Re MA, Manfellotto D, Fuciarelli M (2012) Glutathione S-transferase genes and the risk of recurrent miscarriage in italian women. Fertil Steril 98:396–400

    Article  CAS  PubMed  Google Scholar 

  12. Gallegos-Arreola MP, Ramírez-Patiño R, Sánchez-López JY, Zúñiga-González GM, Figuera LE, Delgado-Saucedo JI, Gómez-Meda BC et al (2022) SOD2 gene variants (rs4880 and rs5746136) and their association with breast cancer risk. Curr Issues Mol Biol 44:5221–5233. https://doi.org/10.3390/cimb44110355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sutton A, Khoury H, Prip-Buus C, Cepanec C, Pessayre D, Degoul F (2003) The Ala16Val genetic dimorphism modulates the import of human manganese superoxide dismutase into rat liver mitochondria. Pharmacogenet 13:145–157. https://doi.org/10.1097/01.fpc.0000054067.64000.8f

    Article  CAS  Google Scholar 

  14. Li Y, Ma C, Wei Y (2017) Relationship between superoxide dismutase 1 and patients with Alzheimer’s disease. Int J Clin Exp Pathol 10:3517–3522

    CAS  Google Scholar 

  15. Crawford A, Fassett RG, Geraghty DP, Kunde DA, Ball MJ, Robertson IK, Coombes JS (2012) Relationships between single nucleotide polymorphisms of antioxidant enzymes and disease. Gene 501:89–103. https://doi.org/10.1016/j.gene.2012.04.011

    Article  CAS  PubMed  Google Scholar 

  16. Otaki Y, Watanabe T, Nishiyama S, Takahashi H, Arimoto T, Shishido T, Miyamoto T (2016) The impact of superoxide dismutase-1 genetic variation on cardiovascular and all-cause mortality in a prospective cohort study: the Yamagata (Takahata). PLoS ONE 11:e0164732. https://doi.org/10.1371/journal.pone.0164732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Noda Y, Ota K, Shirasawa T, Shimizu T (2012) Copper/zinc superoxide dismutase insufficiency impairs progesterone secretion and fertility in female mice. Biol Reprod 86:16–11

    Article  Google Scholar 

  18. Talat TK (2009) The relationship between serum copper, zinc, and glutathione peroxidase with malondialdehyde in women with unexplained recurrent miscarriage. Kufa Med J 12:29–37

    Google Scholar 

  19. Ray A, Bhati T, Pradhan D, Arora R, Parvez S, Rastogi S (2022) Aberrant gene expression of superoxide dismutases in Chlamydia trachomatis-infected recurrent spontaneous aborters. Sci Rep 12:1–2

    Article  Google Scholar 

  20. Singh N, Prasad P, Singh LC, Das B, Rastogi S (2016) Expression of prostaglandin receptors in Chlamydia trachomatis-infected recurrent spontaneous aborters. J Med Microbiol 65:476–483

    Article  CAS  PubMed  Google Scholar 

  21. Ghatak S, Muthukumaran RB, Nachimuthu SK (2013) A simple method of genomic DNA extraction from human samples for PCR-RFLP analysis. J Biomol Tech 24:224. https://doi.org/10.7171/jbt.13-2404-001

    Article  PubMed  PubMed Central  Google Scholar 

  22. George JA, Panchatcharam TS, Paramasivam R (2003) Evaluation of diagnostic efficacy of PCR methods for Chlamydia trachomatis infection in genital and urine specimens of symptomatic men and women in India. Jpn J Infect Dis 56:88–92

    CAS  PubMed  Google Scholar 

  23. Palmer HM, Gilroy CB, Thomas BJ, Hay PE, Gilchrist C, Taylor-Robinson D (1991) Detection of Chlamydia trachomatis by the polymerase chain reaction in swabs and urine from men with non-gonococcal urethritis. J Clin Pathol 44:321–325. https://doi.org/10.1136/jcp.44.4.321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Elham Abdollahi F, Tavasolian N, Ghasemi SA, Mirghanizadeh M, Azizi MG, Morteza Samadi (2015) Association between lower frequency of R381Q variant (rs11209026) in IL-23 receptor gene and increased risk of recurrent spontaneous abortion (RSA). J Immunotoxicol 12(4):317–321. https://doi.org/10.3109/1547691X.2014.978056

    Article  CAS  PubMed  Google Scholar 

  25. Kolor FD, Yousefi JV, Ranjbar R (2021) Molecular evaluation of Chlamydia trachomatis infection and its association with Tumor Necrosis Factor-α polymorphism in recurrent spontaneous abortions.Ethiop J Health Sci31(6)

  26. McCord JM, Edeas MA (2005) SOD, oxidative stress and human pathologies: a brief history and a future vision. Biomed Pharmacothe 59:139–142

    Article  CAS  Google Scholar 

  27. Tošić-Pajić J, Šeklić D, Radenković J, Marković S, Čukić J, Baskić D, Popović S, Todorović M, Sazdanović P (2017) Augmented oxidative stress in infertile women with persistent chlamydial infection. Reprod Biol 17:120–125

    Article  PubMed  Google Scholar 

  28. Nsonwu-Anyanwu AC, Charles-Davies MA, Taiwo VO, Li B, Oni AA, Bello FA (2015) Female reproductive hormones and biomarkers of oxidative stress in genital chlamydia infection in tubal factor infertility. J Reprod Infertil 16:82–89

    PubMed  PubMed Central  Google Scholar 

  29. Nsonwu-Anyanwu AC, Charles-Davies MA, Oni AA, Taiwo VO, Bello FA (2011) Chlamydial infection, plasma peroxidation and obesity in tubal infertility. Ann Ib Postgrad Med 9:83–88

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Bałajewicz-Nowak M, Kazimierz P, Małgorzata M (2011) Antioxidative system in pregnant women infected by Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum. Ginekol Pol 82:732–737

    PubMed  Google Scholar 

  31. Mashkina EV, Kovalenko KA, Miktadova AV, Shkurat MA (2020) Association of Gene polymorphisms of Antioxidants with Reproductive losses. Russ J Genet 56:354–362

    Article  CAS  Google Scholar 

  32. Eskafi Sabet E, Salehi Z, Khodayari S, Sabouhi Zarafshan S, Zahiri Z (2015) Spontaneous abortion and functional polymorphism (Val16Ala) in the manganese SOD gene. J Obstet Gynaecol 35:159–162. https://doi.org/10.3109/01443615.2014.937330

    Article  CAS  PubMed  Google Scholar 

  33. Nguyen H, Syed V (2011) Progesterone inhibits growth and induces apoptosis in cancer cells through modulation of reactive oxygen species. Gynecol Endocrinol 27:830–836. https://doi.org/10.3109/09513590.2010.538100

    Article  CAS  PubMed  Google Scholar 

  34. Bellanti F, Matteo M, Rollo T, De Rosario F, Greco P, Vendemiale G, Serviddio G (2013) Sex hormones modulate circulating antioxidant enzymes: impact of estrogen therapy. Redox Biol 1:340–346. https://doi.org/10.1016/j.redox.2013.05.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Khan A, Khan MZ, Dou J, Xu H, Liu L, Zhu H, Wang Y (2021) SOD1 Gene silencing promotes apoptosis and suppresses proliferation of heat-stressed bovine granulosa cells via induction of oxidative stress. Vet Sci 8:326. doi.10.3390/vetsci8120326

  36. Azenabor AA, Kennedy P, Balistreri S (2007) Chlamydia trachomatis infection of human trophoblast alters estrogen and progesterone biosynthesis: an insight into role of infection in pregnancy sequelae. Int J Med Sci 4:223–231. https://doi.org/10.7150/ijms.4.223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Brown M, Rae M, Wheelhouse N (2021) Chlamydia inhibits progesterone receptor mRNA expression in SHT-290 cells. Reprod Fertil 2:L9–11. https://doi.org/10.1530/RAF-2-0069

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

AR and TB are thankful to University Grants Commission (UGC), Government of India for the award of Senior Research Fellowship.

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Authors and Affiliations

  1. Molecular Microbiology laboratory, ICMR-National Institute of Pathology, Sriramachari Bhawan, Safdarjung hospital campus, Post Box no. 4909, New Delhi, 110029, India

    Ankita Ray, Tanu Bhati & Sangita Rastogi

  2. Department of Obstetrics and Gynecology, Vardhman Mahavir Medical College (VMMC) and Safdarjung hospital, New Delhi, 110029, India

    Renu Arora

  3. Department of Medical Elementology and Toxicology, Jamia Hamdard, New Delhi, 110062, India

    Ankita Ray, Tanu Bhati & Suhel Parvez

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Contributions

AR designed and performed experiments, data analysis, original draft writing and editing. TB performed experiments and data analysis. RA did clinical sampling, review and editing. Original draft writing, review and editing were done by SP. Project conceptualization, administration, methodology, data curation, original draft writing, review and editing were done by SR. All authors read and approved the final manuscript.

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Correspondence to Sangita Rastogi.

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The authors declare no competing interests.

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Ethical approval was granted by the Ethics Committee of Vardhman Mahavir Medical College and Safdarjung hospital, New Delhi, India (IEC/VMMC/SJH/Project/2019/08/42).

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Informed consent was obtained from all individual participants included in the study.

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Ray, A., Bhati, T., Arora, R. et al. Association of functional superoxide gene polymorphism with chlamydia trachomatis-associated recurrent spontaneous abortion. Mol Biol Rep 50, 4907–4915 (2023). https://doi.org/10.1007/s11033-023-08405-5

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