Correlation of Sperm Mitochondrial DNA 7345 bp and 7599 bp Deletions with Asthenozoospermia in Jordanian Population

Al Zoubi, Mazhar; Al-Talafha, Ali M.; Al Sharu, Emad; Al-Trad, Bahaa; AlZu&#039;bi, Ayman; AbuAlarjah, Manal; Shehab, Qasem; Alsmadi, Mohammad; Al-Batayneh, Khalid M.

doi:10.18502/jri.v22i3.6717

Correlation of Sperm Mitochondrial DNA 7345 bp and 7599 bp Deletions with Asthenozoospermia in Jordanian Population

Authors

Mazhar Al Zoubi ¹

Ali M. Al-Talafha ²

Emad Al Sharu ³

Bahaa Al-Trad ⁴

Ayman AlZu'bi ¹

Manal AbuAlarjah ¹

Qasem Shehab ⁵

Mohammad Alsmadi ⁶

Khalid M. Al-Batayneh ²

¹ Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan

² Department of Biological Sciences, Faculty of Science, Yarmouk University, Irbid, Jordan

³ King Hussein Medical Centre, Royal Medical Services, Amman, Jordan

⁴ Department of Biological Sciences, Faculty of Science, Yarmouk University, Ibadan, Jordan

⁵ Department of Clinical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan

⁶ Department of Gynecology and Reproductive Medicine, Faculty of Medicine, Saarland University, Saarbrücken, Germany

10.18502/jri.v22i3.6717

Abstract

Background: Alterations in sperm mitochondrial DNA (mtDNA) affect the functions of some OXPHOS proteins which will affect sperm motility and may be associated with asthenozoospermia. The purpose of this study was to investigate the correlation between 7599-bp and 7345-bp sperm mtDNA deletions and asthenozoospermia in Jordan. Methods: Semen specimens from 200 men including 121 infertile and 79 healthy individuals were collected at the Royal Jordanian Medical Services In-vitro fertilization (IVF) units. The mtDNA was extracted followed by mtDNA amplification. Polymerase chain reaction (PCR) was conducted for the target sequences, then DNA sequencing was performed for the PCR products. Chi-square, Fisher's and Spearman's tests were used to calculate the correlation. Results: The results showed a significant correlation between the presence of 7599-bp mtDNA deletion and infertility where the frequency of the 7599-bp deletion was 63.6 % in the infertile group compared to the fertile 34.2% (p<0.001, (OR=3.37, 95% CI=1.860 to 6.108)). Additionally, the sperm motility showed a significant association with the frequency of the 7599-bp deletion (p=0.001, r=-0.887). The 7345-bp mtDNA deletion showed no assoctiation with the infertility (p=0.65, (OR=0.837, 95% CI=0.464-1.51)) or asthenozoospermia (p=0.98, r=0.008). Conclusion: We demonstrated a significant correlation between asthenozoospermia and the 7599-bp mtDNA deletion but not the 7345-bp mtDNA deletion in the infertile men in Jordan. Screening for deletions in sperm mtDNA can be used as a pre-diagnostic molecular marker for male infertility.

Keywords

Asthenozoospermia

Gene deletion

Male infertility

Mitochondrial DNA

sperm motility

Brugo-Olmedo S, Chillik C, Kopelman S. Definition and causes of infertility. Reprod Biomed Online. 2001;2(1):41-53.

Demain LA, Conway GS, Newman WG. Genetics of mitochondrial dysfunction and infertility. Clin Genet. 2017;91(2):199-207.

Hull MG, Glazener CM, Kelly NJ, Conway DI, Foster PA, Hinton RA, et al. Population study of causes, treatment, and outcome of infertility. Br Med J (Clin Res Ed). 1985;291(6510):1693-7.

Kumar N, Singh AK. Trends of male factor infertility, an important cause of infertility: a review of literature. J Hum Reprod Sci. 2015;8(4):191-6.

Wang C, Swerdloff RS. Limitations of semen analysis as a test of male fertility and anticipated needs from newer tests. Fertil Steril. 2014;102(6):1502-7.

Ortega C, Verheyen G, Raick D, Camus M, Devroey P, Tournaye H. Absolute asthenozoospermia and ICSI: what are the options? Hum Reprod Update. 2011;17(5):684-92.

Baker HW, Clarke GN. Sperm morphology: consistency of assessment of the same sperm by different observers. Clin Reprod Fertil. 1987;5(1-2):37-43.

Amaral A, Lourenco B, Marques M, Ramalho-Santos J. Mitochondria functionality and sperm quality. Reproduction. 2013;146(5):R163-74.

Kao SH, Chao HT, Wei YH. Multiple deletions of mitochondrial DNA are associated with the decline of motility and fertility of human spermatozoa. Mol Hum Reprod. 1998;4(7):657-66.

Ambulkar PS, Waghmare JE, Chaudhari AR, Wankhede VR, Tarnekar AM, Shende MR, et al. Large scale 7436-bp deletions in human sperm mitochondrial DNA with spermatozoa dysfunction and male infertility. J Clin Diagn Res. 2016;10(11):GC09-GC12.

Pandey R, Mehrotra D, Catapano C, Choubey V, Sarin R, Mahdi AA, et al. Association of mitochondrial deoxyribonucleic acid mutation with polymorphism in CYP2E1 gene in oral carcinogenesis. J Oral Biol Craniofacial Res. 2012;2(1):4-9.

Kao S, Chao HT, Wei YH. Mitochondrial deoxyribonucleic acid 4977-bp deletion is associated with diminished fertility and motility of human sperm. Biol Reprod. 1995;52(4):729-36.

Aitken RJ, Clarkson JS. Significance of reactive oxygen species and antioxidants in defining the efficacy of sperm preparation techniques. J Androl. 1988;9(6):367-76.

Shamsi MB, Kumar R, Bhatt A, Bamezai RN, Kumar R, Gupta NP, et al. Mitochondrial DNA mutations in etiopathogenesis of male infertility. Indian J Urol. 2008;24(2):150-4.

St John JC, Jokhi RP, Barratt CL. Men with oligoasthenoteratozoospermia harbour higher numbers of multiple mitochondrial DNA deletions in their spermatozoa, but individual deletions are not indicative of overall aetiology. Mol Hum Reprod. 2001;7(1):103-11.

Talebi E, Karimian M, Nikzad H. Association of sperm mitochondrial DNA deletions with male infertility in an Iranian population. Mitochondrial DNA A DNA Mapp Seq Anal. 2018;29(4):615-23.

Marmor D, Grob‐Menendez F. Male infertility due to asthenozoospermia and flagellar anomaly: detection in routine semen analysis. Int J Androl. 1991;14(2):108-16.

Bahrehmand Namaghi I, Vaziri H. Sperm mitochondrial DNA deletion in Iranian infertiles with asthenozoospermia. Andrologia. 2017;49(3).

World Health Organisation. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: World Health Organisation; 2010. 286 p.

Ieremiadou F, Rodakis GC. Correlation of the 4977 bp mitochondrial DNA deletion with human sperm dysfunction. BMC Res Notes. 2009;2:18.

Gibbons I. Sperm motility: mechanisms and control. In: Andre J, editor. The Sperm Cell. Berlin: Springer; 1983. p. 304-14.

Bornstein B, Huertas R, Ochoa P, Campos Y, Guillen F, Garesse R, et al. Mitochondrial gene expression and respiratory enzyme activities in cardiac diseases. Biochim Biophys Acta. 1998;1406(1):85-90.

Hecht NB, Liem H, Kleene KC, Distel RJ, Ho Sm. Maternal inheritance of the mouse mitochondrial genome is not mediated by a loss or gross alteration of the paternal mitochondrial DNA or by methylation of the oocyte mitochondrial DNA. Dev Biol. 1984;102(2):452-61.

Aitken RJ. Human spermatozoa: revelations on the road to conception. F1000prime Rep. 2013;5:39.

Al Zoubi MS, Al‐Batayneh K, Alsmadi M, Rashed M, Al‐Trad B, Al Khateeb W, et al. 4,977‐bp human mitochondrial DNA deletion is associated with asthenozoospermic infertility in Jordan. Andrologia. 2020;52(1):e13379.

Hosseinzadeh Colagar A, Karimi F. Large scale deletions of the mitochondrial DNA in astheno, asthenoterato and oligoasthenoterato-spermic men. Mitochondrial DNA. 2014;25(4):321-8.

Phillips NR, Sprouse ML, Roby RK. Simultaneous quantification of mitochondrial DNA copy number and deletion ratio: a multiplex real-time PCR assay. Sci Rep. 2014;4:3887.