Semen mikrobiatasının semen parametreleri ve erkek infertilitesi ile ilişkisi

İnsanlarda bulunan mikroorganizmaların (bakteri, virüs, mantar) tamamına “mikrobiata”, tüm bu mikroorganizmaların genomuna “mikrobiyom” adı verilmektedir. Bugüne kadar insanlarda 10.000’den fazla bakteri ve mantar, 3000’den fazla virüs türü saptanmıştır. İnsan mikrobiatasının %9u ürogenital sistemde olup hem fertil hem de infertil erkeklerde semenin mikrobiata nedeniyle steril olmadığı bilinmektedir. Prevotella, Finegoldia, Psödomonas, Peptinophilus, Streptococcus, Anaerococcus, Lactobacillus ve Corynebacterium bakteri cinsleri sperm mikrobiyomunun en sık saptanan ana mikrobiata bileşenleri olarak kabul edilmektedir. Semen mikrobiatasının semen parametreleri ile ilişkisi ise halen net olmasa da bakteriyosperminin sperm sayısı, motilitesi ve sperm DNA fragmantasyonu üzerinde olumsuz etkisinin olduğu bilinmektedir. Ancak özellikle NGS (next-generation DNA sequencing) tekniği kullanılan çalışmalarda hem fertil hem de infertil hastaların semen mikrobiataları benzer bulunmuştur. Ancak intratestiküler dokuların standart kültür yöntemlerine göre steril olmasına rağ- men mTESE işlemi ile sperm bulunamayan hastaların intratestiküler dokusunda Firmicutes ve Clostridia türlerinin düşük, Peptoniphilus türünün tamamen yok ve Actinobacteria türünün ise yüksek oranda saptanmaktadır. Ayrıca yardımcı üreme teknikleri ile elde edilen embriyonlar semen mikrobiyatasında Enterobacteriaceae varlığında daha iyi, Alphaproteobacteria ve Gammaproteobacteria varlığında ise daha düşük kaliteli gelişim göstermektedir. Probiyotik kullanımının semende ROS miktarında 3,5 katlık azalma ve sperm motilitesinde altı katlık bir artış sağladığı gösterilse de probiyotik kullanımı ve semen parametreleri arasındaki ilişki halen net değildir. Sonuç olarak semen mikrobiatasının erkek infertilitesi ile ilişkisi mevcut sınırlı kanıtlar göz önüne alındığında halen yeterli olmayıp gelişen teknoloji ve bilgi birikimi ile koruyucu rolü olabilecek patojenik olmayan mikrobiatal organizmaların idiyopatik erkek infertilitesinin tedavisindeki rolü gelecekteki araştırmalar ile aydınlatılmalıdır.

The relationship of semen microbiota with semen parameters and male infertility

All of the microorganisms (bacteria, viruses, fungi) found in humans are called “microbiota”, and the genomes of all these microorganisms are called “microbiomes”. To date, more than 10,000 types of bacteria and fungi, and more than 3000 types of viruses have been identified in humans. Nine percent of human microbiota is present in the urogenital system and it is known that semen in both fertile and infertile men is not sterile due to microbiota. Prevotella, Finegoldia, Pseudomonas, Peptinophilus, Streptococcus, Anaerococcus, Lactobacillus and Corynebacterium bacterial genera are considered to be the most frequently detected major microbiota components of the sperm microbiome. Although the relationship between semen microbiota and semen parameters is still not clear, it is known that bacteriospermia has a negative effect on sperm count, motility and sperm DNA fragmentation. However, especially in studies using NGS (nextgeneration DNA sequencing) technique, semen microbiota of both fertile and infertile patients were found to be similar. Although intratesticular tissues are sterile according to standard culture methods, Firmicutes and Clostridia species are found to be low, Peptoniphilus species completely absent and Actinobacteria species are found to be high in intratesticular tissue of patients who cannot find sperm by mTESE procedure. In addition, embryos obtained by assisted reproduction techniques show better growth in the presence of Enterobacteriaceae in the semen microbiota, but lower quality in the presence of Alphaproteobacteria and Gammaproteobacteria. Although it has been shown that the use of probiotics provides a 3.5-fold decrease in the amount of ROS in semen and a six-fold increase in sperm motility, the relationship between probiotic use and semen parameters is still unclear. In conclusion, the relationship between semen microbiota and male infertility is still not sufficient considering the limited evidence available. With the developing technology and knowledge, the role of non-pathogenic microbiatal organisms that may have a protective role in the treatment of idiopathic male infertility should be evaluated by future research.

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  • 1. Rowe P, Comhaire F, Hargreave T, Mahmoud AMA, editors. WHO manual for the standardized investigation and diagnosis of the infertile couple. Press Syndicate of the University of Cambridge, Cambridge, 1993.
  • 2. Agarwal A, Parekh N, Selvam MKP, Henkel R, Shah R, Homa ST, et al. Male oxidative stress infertility (MOSI): proposed terminology and clinical practice guidelines for management of idiopathic male infertility. World J Mens Health. 2019;37:296– 312. [CrossRef]
  • 3. Pellati D, Mylonakis I, Bertoloni G, Fiore C, Andrisani A, Ambrosini G, Armanini D. Genital tract infections and infertility. Eur J Obstet Gynecol Reprod Biol. 2008;140:3–11. [CrossRef]
  • 4. Domes T, Lo KC, Grober ED, Mullen JBM, Mazzulli T, Jarvi K. The incidence and effect of bacteriospermia and elevated seminal leukocytes on semen parameters. Fertil Steril. 2012;97:1050–5. [CrossRef]
  • 5. Agarwal A, Sharma RK, Sharma R, Assidi M, Abuzenadah AM, Alshahrani S, et al. Characterizing semen parameters and their association with reactive oxygen species in infertile men. Reprod Biol Endocrinol. 2014;12:33. [CrossRef]
  • 6. Yao Y, Qiu X-J, Wang D-S, Luo J-K, Tang T, Li Y-H, et al. Semen microbiota in normal and leukocytospermic males. Asian J Androl. 2022;24:398–405. [CrossRef]
  • 7. Moya AS. Microbiome and next generation sequencing. Rev Esp Quimioter. 2017;30:305–11. https://seq.es/seq/0214-3429/30/5/ suarez17jul2017.pdf
  • 8. Gachet C, Prat M, Burucoa C, Grivard P, Pichon M. Spermatic microbiome characteristics in infertile patients: impact on sperm count, mobility, and morphology. J Clin Med. 2022;11:1505. [CrossRef]
  • 9. Frank DN, St. Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A. 2007;104:13780–5. [CrossRef]
  • 10. Moreno I, Codoñer FM, Vilella F, Valbuena D, Martinez-Blanch JF, Jimenez-Almazán J, et al. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet Gynecol. 2016;215:684–703. [CrossRef]
  • 11. Pergialiotis V, Karampetsou N, Perrea DN, et al. The impact of bacteriospermia on semen parameters: a meta-analysis. J Family Reprod Health. 2018;12:73–83. https://www.ncbi.nlm.nih.gov/ pmc/articles/PMC6391301/
  • 12. Chen H, Luo T, Chen T, Wang G. Seminal bacterial composition in patients with obstructive and non-obstructive azoospermia. Exp Ther Med. 2018;15:2884–90. [CrossRef]
  • 13. Chen H, Shi X, Li X, Diao R, Ma Q, Jin J, et al. CD147 deficiency is associated with impaired sperm motility/acrosome reaction and offers a therapeutic target for asthenozoospermia. Mol Ther Nucleic Acids. 2021;26:1374–86. [CrossRef]
  • 14. López Hurtado M, Velazco Fernández M, Pedraza Sánchez M, Flores-Salazar VR, Zesati RV, Guerra-Infante FM. Molecular detection of Chlamydia trachomatis and semen quality of sexual partners of infertile women. Andrologia. 2018;50:e12812. [CrossRef]
  • 15. Farahani L, Tharakan T, Yap T, Ramsay JW, Jayasena CN, Minhas S. The semen microbiome and its impact on sperm function and male fertility: a systematic review and meta analysis. Andrology. 2021;9:115–44. [CrossRef]
  • 16. Hou D, Zhou X, Zhong X, Settles ML, Herring J, Wang L, et al. Microbiota of the seminal fluid from healthy and infertile men. Fertility and sterility. 2013;100:1261–9. [CrossRef]
  • 17. Weng S-L, Chiu C-M, Lin F-M, Huang W-C, Liang C, Yang T, et al. Bacterial communities in semen from men of infertile couples: metagenomic sequencing reveals relationships of seminal microbiota to semen quality. PloS One. 2014;9:e110152. [CrossRef]
  • 18. Monteiro C, Marques PI, Cavadas B, Damião I, Almeida V, Barros N, et al. Characterization of microbiota in male infertility cases uncovers differences in seminal hyperviscosity and oligoasthenoteratozoospermia possibly correlated with increased prevalence of infectious bacteria. Am J Reprod Immunol. 2018;79:e12838. [CrossRef]
  • 19. Mändar R, Türk S, Korrovits P, Ausmees K, Punab M. Impact of sexual debut on culturable human seminal microbiota. Andrology. 2018;6:510–2. [CrossRef]
  • 20. Venneri M, Franceschini E, Sciarra F, Rosato E, D’Ettorre G, Lenzi A. Human genital tracts microbiota: Dysbiosis crucial for infertility. J Endocrinol Invest. 2022;45:1151–60. [CrossRef]
  • 21. Mashaly M, Masallat D, Elkholy A, Abdel-Hamid IA, Mostafa T. Seminal Corynebacterium strains in infertile men with and without leucocytospermia. Andrologia. 2016;48:355–9. [CrossRef]
  • 22. Zeyad A, Hamad M, Amor H, et al. Relationships between bacteriospermia, DNA integrity, nuclear protamine alteration, sperm quality and ICSI outcome. Reprod Biol. 2018;18:115–21. [CrossRef]
  • 23. Nasrallah YS, Anani M, Omar HH, Hammadeh ME. Microbiological profiles of semen culture in male infertility. Human Andrology. 2018;8:34–42. [CrossRef]
  • 24. Ma X-P, Gao X-Q. The effect of Ureaplasma urealyticum on the level of P34H expression, the activity of hyaluronidase, and DNA fragmentation in human spermatozoa. Am J Reprod Immunol. 2017;77:e12600. [CrossRef]
  • 25. Bukharin OV, Perunova NB, Ivanova EV, Chaynikova IN, Bekpergenova AV, Bondarenko TA, Kuzmin MD. Semen microbiota and cytokines of healthy and infertile men. Asian J Androl. 2022;24:353–8. [CrossRef]
  • 26. Vilvanathan S, Kandasamy B, Jayachandran AL, Sathiyanarayanan S, Singaravelu VT, Krishnamurthy V, Elangovan V. Bacteriospermia and its impact on basic semen parameters among infertile men. Interdiscip Perspect Infect Dis. 2016;2016:2614692. [CrossRef]
  • 27. Baud D, Pattaroni C, Vulliemoz N, Castella V, Marsland BJ, Stojanov M. Sperm microbiota and its impact on semen parameters. Front Microbiol. 2019;10:234. [CrossRef]
  • 28. Fraczek M, Wiland E, Piasecka M, Boksa M, Gaczarzewicz D, Szumala-Kakol A, et al. Fertilizing potential of ejaculated human spermatozoa during in vitro semen bacterial infection. Fertil Steril. 2014;102:711–9.e1. [CrossRef]
  • 29. Fraczek M, Hryhorowicz M, Gaczarzewicz D, Szumala-Kakol A, Kolanowski TJ, Beutin L, Kurpisz M. Can apoptosis and necrosis coexist in ejaculated human spermatozoa during in vitro semen bacterial infection? J Assist Reprod Genet. 2015;32:771–9. [CrossRef]
  • 30. Al Sweih NA, Al Fadli AH, Omu AE, Rotimi VO. Prevalence of Chlamydia trachomatis, Mycoplasma hominis, Mycoplasma genitalium, and Ureaplasma urealyticum infections and seminal quality in infertile and fertile men in Kuwait. J Androl. 2012;33:1323–9. [CrossRef]
  • 31. Liu J, Wang Q, Ji X, Guo S, Dai Y, Zhang Z, et al. Prevalence of Ureaplasma urealyticum, Mycoplasma hominis, Chlamydia trachomatis infections, and semen quality in infertile and fertile men in China. Urology. 2014;83:795–9. [CrossRef]
  • 32. Kiessling AA, Desmarais BM, Yin H-Z, Loverde J, Eyre RC. Detection and identification of bacterial DNA in semen. Fertil Steril. 2008;90:1744–56. [CrossRef]
  • 33. Amato V, Papaleo E, Pasciuta R, Viganò P, Ferrarese R, Clementi N, et al., editors. Differential composition of vaginal microbiome, but not of seminal microbiome, is associated with successful intrauterine insemination in couples with idiopathic infertility: a prospective observational study. Open Forum Infect Dis. 2020;7:ofz525. [CrossRef]
  • 34. Štšepetova J, Baranova J, Simm J, Parm Ü, Rööp T, Sokmann S, Korrovits P, et al. The complex microbiome from native semen to embryo culture environment in human in vitro fertilization procedure. Reprod Biol Endocrinol. 2020;18:3. [CrossRef]
  • 35. Alfano M, Ferrarese R, Locatelli I, Ventimiglia E, Ippolito S, Gallina P, et al. Testicular microbiome in azoospermic men-first evidence of the impact of an altered microenvironment. Hum Reprod. 2018;33:1212–7. [CrossRef]
  • 36. Mastromarino P, Macchia S, Meggiorini L, Trinchieri V, Mosca L, Perluigi M, Midulla C. Effectiveness of Lactobacillus-containing vaginal tablets in the treatment of symptomatic bacterial vaginosis. Clin Microbiol Infect. 2009;15:67–74. [CrossRef]
  • 37. Barbonetti A, Cinque B, Vassallo MRC, Mineo S, Francavilla S, Cifone MG, Francavilla F. Effect of vaginal probiotic lactobacilli on in vitro-induced sperm lipid peroxidation and its impact on sperm motility and viability. Fertil Steril. 2011;95:2485–8. [CrossRef]
  • 38. Chen X, Gong L, Xu J. Antioxidative activity and protective effect of probiotics against high-fat diet-induced sperm damage in rats. Animal. 2013;7:287–92. [CrossRef]
  • 39. Valcarce D, Genovés S, Riesco M, Martorell P, Herráez MP, Ramón D, Robles V. Probiotic administration improves sperm quality in asthenozoospermic human donors. Benef Microbes. 2017;8:193– 206. [CrossRef]
  • 40. Helli B, Kavianpour M, Ghaedi E, Dadfar M, Haghighian HK. Probiotic effects on sperm parameters, oxidative stress index, inflammatory factors and sex hormones in infertile men. Hum Fertil (Camb). 2020;25:499–507. [CrossRef]