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Oligozoospermi ve Şiddetli Oligozoospermi Olan Bireylerin Sperminde Heat Shock Protein 70 (HSP70) Ekspresyonundaki Değişiklikler

Year 2025, Volume: 6 Issue: 2, 160 - 172, 29.07.2025
https://doi.org/10.46871/eams.1648052

Abstract

Aim:Infertility, defined as the inability to achieve pregnancy after one year of regular, unprotected sexual intercourse, is categorized as either female or male infertility. Male infertility is often associated with impairments in sperm quality and function. Heat shock proteins (HSPs), particularly HSP70, play a critical role as molecular chaperones, protecting cells from stress-induced damage by stabilizing proteins and ensuring proper folding. However, the relationship between HSP70 expression and male infertility has not been fully elucidated. This study aimed to investigate HSP70 expression in sperm samples from individuals with normal, oligozoospermic, and severe oligozoospermic profiles using immunocytochemical techniques.
Material and Methods: Sperm samples were obtained from the In Vitro Fertilization Unit of *** University and divided into three groups: Control (>20 million/ml sperm), Oligozoospermic (<15 million/ml), and Severe Oligozoospermic (<5 million/ml). Samples were stained for HSP70, and hormone levels (testosterone, FSH, and LH) were evaluated.
Results: HSP70 expression was significantly elevated in the Oligozoospermic group compared to the Control group but decreased in the Severe Oligozoospermic group, reaching levels comparable to the Control group. Hormonal analyses revealed altered levels of testosterone, FSH, and LH in both oligozoospermic groups.
Conclusion: These findings suggest increased HSP70 expression in oligozoospermic individuals reflects intracellular disruptions, potentially linked to hormonal dysregulation and organ dysfunction. Such alterations may affect sperm parameters, including morphology, motility, and count. While this study demonstrates a relationship between HSP70 expression and sperm abnormalities under stress conditions, further research is needed to confirm these mechanisms and explore their broader implications.

Project Number

yok

References

  • 1. Fainberg J, Kashanian JA. Recent advances in understanding and managing male infertility. F1000Res. 2019;16;8:F1000 Faculty Rev-670.
  • 2. Durairajanayagam D. Lifestyle causes of male infertility. Arab J Urol 2018; 16(1):10-20.
  • 3. Raheem A, Ralph D. Male infertility: causes and investigations. Trends Urol Men’s Health 2011; 2(5):8-11.
  • 4. Minhas S, Bettocchi C, Boeri L, Capogrosso P, Carvalho J, Cilesiz NC, et al. European Association of Urology Guidelines on Male Sexual and Reproductive Health: 2021 Update on Male Infertility. Eur Urol 2021;80(5):603- 620.
  • 5. World Health Organization. WHO laboratory manual for the examination and processing of human semen, 5th edition, Geneva, World Health Organization, 2010;6:46-53.
  • 6. Wang W, Vinocur B, Shoseyov O, Altman A. Role of plant heat-shock proteins and molecular chaperones in the abiotic stress response. Trends Plant Sci 2004; 9(5):244-52.
  • 7. Hüttner S, Strasser R. Endoplasmic reticulumassociated degradation of glycoproteins in plants. Front Plant Sci 2012; 3:67.
  • 8. Feder ME, Hofmann GE. Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology. Annu Rev Physiol 1999; 61:243-82.
  • 9. Henle KJ, Jethmalani SM, Nagle WA. Stress proteins and glycoproteins (Review). Int J Mol Med 1998; 1(1):25-32.
  • 10. Albakova Z, Mangasarova Y, Albakov A, Gorenkova L. HSP70 and HSP90 in Cancer: Cytosolic, Endoplasmic Reticulum and Mitochondrial Chaperones of Tumorigenesis. Front Oncol 2022; 12:829520.
  • 11. Dix DJ. Hsp70 expression and function during gametogenesis. Cell Stress Chaperones 1997; 2(2):73-7.
  • 12. Hasi G, Wu L, Sodnompil T, Yi R, Wu R, Zhang R, et al.. Differential expression and localisation of heat shock protein 70 (HSP70) and glutathione peroxidase 5 (GPX5) in the testis and epididymis of Sonid Bactrian camels. Reprod Fertil Dev 2023; 35(10):552-562.
  • 13. WHO TEAM: Sexual and Reproductive Health and Research. Infertility Prevalence Estimates, 1990–2021 (WHO, 2023).
  • 14. Thonneau P, Marchand S, Tallec A, Ferial ML, Ducot B, Lansac J, et al. Incidence and main causes of infertility in a resident population (1,850,000) of three French regions (1988-1989). Hum Reprod 1991; 6(6):811-6.
  • 15. Agarwal A, Mulgund A, Hamada A, Chyatte MR. A unique view on male infertility around the globe. Reprod Biol Endocrinol 2015; 13:37.
  • 16. Eisenberg ML, Esteves SC, Lamb DJ, Hotaling JM, Giwercman A, Hwang K, et al. Male infertility. Nat Rev Dis Primers 2023; 9(1):49.
  • 17. Kaltsas A. Oxidative Stress and Male Infertility: The Protective Role of Antioxidants. Medicina (Kaunas). 2023; 59(10):1769.
  • 18. O'Flaherty C. Reactive Oxygen Species and Male Fertility. Antioxidants (Basel) 2020; 9(4):287.
  • 19. Tapısız ÖL, Altınbaş SK, Abike F, Göktolga Ü. Jinekolog gözü ile semen analizi ve son gelişmeler. Turk J Obstet Gynecol 2012;1(9);25-31.
  • 20. Schlegel PN, Sigman M, Collura B, De Jonge CJ, Eisenberg ML, Lamb DJ, et al. Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline Part I. J Urol 2021;205(1):36-43.
  • 21. Dohle GR, Smit M, Weber RF. Androgens and male fertility. World J Urol 2003; 21(5):341-5.
  • 22. Khodamoradi K, Parmar M, Khosravizadeh Z, Kuchakulla M, Manoharan M, Arora H. The role of leptin and obesity on male infertility. Curr Opin Urol 2020; 30(3):334-339.
  • 23. Coviello AD, Matsumoto AM, Bremner WJ, Herbst KL, Amory JK, Anawalt BD, et al. Lowdose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression. J Clin Endocrinol Metab 2005; 90(5):2595-602.
  • 24. Jarow JP, Chen H, Rosner TW, Trentacoste S, Zirkin BR. Assessment of the androgen environment within the human testis: minimally invasive method to obtain intratesticular fluid. J Androl 2001; 22(4):640-5.
  • 25. Emmanuel M, Bokor BR. Tanner Stages. 2022. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 – ID: NBK470280.
  • 26. de Kretser DM. Editorial: Is spermatogenic damage associated with Leydig cell dysfunction? J Clin Endocrinol Metab 2004;89(7):3158-60.
  • 27. Koukkou E, Billa E, Kapolla N, Pappa A, Venaki E, Andreou L, et al. An empiric treatment for idiopathic oligozoospermia revisited: a 20-year investigative saga. Andrologia 2012; 44(5):337-42.
  • 28. Kontaş T, Ergün N, Turunç V. Isı şok proteinler ve fizyolojik rolleri. Kafkas Üniv Vet Fak Derg 2007; 13 (1): 109-114.
  • 29. Volloch VZ, Sherman MY. Oncogenic potential of Hsp72. Oncogene 1999;18(24):3648-51.
  • 30. Ferlin A, Speltra E, Patassini C, Pati MA, Garolla A, Caretta N, et al. Heat shock protein and heat shock factor expression in sperm: relation to oligozoospermia and varicocele. J Urol 2010; 183(3):1248-52.
  • 31. Dangi SS, Gupta M, Maurya D, Yadav VP, Panda RP, Singh G, et al. Expression profile of HSP genes during different seasons in goats (Capra hircus). Trop Anim Health Prod 2012; 44(8):1905-12.
  • 32. Chung L, Ng YC. Age-related alterations in expression of apoptosis regulatory proteins and heat shock proteins in rat skeletal muscle. Biochim Biophys Acta 2006; 1762(1):103-9.
  • 33. Jannatifar R, Cheraghi E, Nasr-Esfahani MH, Piroozmanesh H. Association of heat shock protein A2 expression and sperm quality after N-acetyl-cysteine supplementation in asthenoterato-zoospermic infertile men. Andrologia 2021; 53(5):e14024.
  • 34. Spinaci M, Volpe S, Bernardini C, De Ambrogi M, Tamanini C, Seren E, et al. Immunolocalization of heat shock protein 70 (Hsp 70) in boar spermatozoa and its role during fertilization. Mol Reprod Dev 2005; 72(4):534-41.
  • 35. Erata GO, Koçak Toker N, Durlanik O, Kadioğlu A, Aktan G, Aykaç Toker G. The role of heat shock protein 70 (Hsp 70) in male infertility: is it a line of defense against sperm DNA fragmentation? Fertil Steril 2008;90(2):322-7.
  • 36. Bak CW, Song SH, Yoon TK, Lim JJ, Shin TE, Sung S. Natural course of idiopathic oligozoospermia: comparison of mild, moderate and severe forms. Int J Urol 2010; 17(11):937-43.
  • 37. Yin Y, Cao S, Fu H, Fan X, Xiong J, Huang Q, et al. A noncanonical role of NOD-like receptor NLRP14 in PGCLC differentiation and spermatogenesis. Proc Natl Acad Sci USA 2020; 117(36):22237-48.

Alterations in Heat Shock Protein 70 (Hsp70) Expression in Sperm of Individuals with Oligozoospermia and Severe Oligozoospermia

Year 2025, Volume: 6 Issue: 2, 160 - 172, 29.07.2025
https://doi.org/10.46871/eams.1648052

Abstract

Aim:Infertility, defined as the inability to achieve pregnancy after one year of regular, unprotected sexual intercourse, is categorized as either female or male infertility. Male infertility is often associated with impairments in sperm quality and function. Heat shock proteins (HSPs), particularly HSP70, play a critical role as molecular chaperones, protecting cells from stress-induced damage by stabilizing proteins and ensuring proper folding. However, the relationship between HSP70 expression and male infertility has not been fully elucidated. This study aimed to investigate HSP70 expression in sperm samples from individuals with normal, oligozoospermic, and severe oligozoospermic profiles using immunocytochemical techniques.
Material and Methods: Sperm samples were obtained from the In Vitro Fertilization Unit of *** University and divided into three groups: Control (>20 million/ml sperm), Oligozoospermic (<15 million/ml), and Severe Oligozoospermic (<5 million/ml). Samples were stained for HSP70, and hormone levels (testosterone, FSH, and LH) were evaluated.
Results: HSP70 expression was significantly elevated in the Oligozoospermic group compared to the Control group but decreased in the Severe Oligozoospermic group, reaching levels comparable to the Control group. Hormonal analyses revealed altered levels of testosterone, FSH, and LH in both oligozoospermic groups.
Conclusion: These findings suggest increased HSP70 expression in oligozoospermic individuals reflects intracellular disruptions, potentially linked to hormonal dysregulation and organ dysfunction. Such alterations may affect sperm parameters, including morphology, motility, and count. While this study demonstrates a relationship between HSP70 expression and sperm abnormalities under stress conditions, further research is needed to confirm these mechanisms and explore their broader implications.

Ethical Statement

Ethical approval for this study was obtained from the *** Clinical Research Ethics Committee (approval number: 2022/191, dated 23.02.2022).

Supporting Institution

this study did not receive any financial support from any institution.

Project Number

yok

References

  • 1. Fainberg J, Kashanian JA. Recent advances in understanding and managing male infertility. F1000Res. 2019;16;8:F1000 Faculty Rev-670.
  • 2. Durairajanayagam D. Lifestyle causes of male infertility. Arab J Urol 2018; 16(1):10-20.
  • 3. Raheem A, Ralph D. Male infertility: causes and investigations. Trends Urol Men’s Health 2011; 2(5):8-11.
  • 4. Minhas S, Bettocchi C, Boeri L, Capogrosso P, Carvalho J, Cilesiz NC, et al. European Association of Urology Guidelines on Male Sexual and Reproductive Health: 2021 Update on Male Infertility. Eur Urol 2021;80(5):603- 620.
  • 5. World Health Organization. WHO laboratory manual for the examination and processing of human semen, 5th edition, Geneva, World Health Organization, 2010;6:46-53.
  • 6. Wang W, Vinocur B, Shoseyov O, Altman A. Role of plant heat-shock proteins and molecular chaperones in the abiotic stress response. Trends Plant Sci 2004; 9(5):244-52.
  • 7. Hüttner S, Strasser R. Endoplasmic reticulumassociated degradation of glycoproteins in plants. Front Plant Sci 2012; 3:67.
  • 8. Feder ME, Hofmann GE. Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology. Annu Rev Physiol 1999; 61:243-82.
  • 9. Henle KJ, Jethmalani SM, Nagle WA. Stress proteins and glycoproteins (Review). Int J Mol Med 1998; 1(1):25-32.
  • 10. Albakova Z, Mangasarova Y, Albakov A, Gorenkova L. HSP70 and HSP90 in Cancer: Cytosolic, Endoplasmic Reticulum and Mitochondrial Chaperones of Tumorigenesis. Front Oncol 2022; 12:829520.
  • 11. Dix DJ. Hsp70 expression and function during gametogenesis. Cell Stress Chaperones 1997; 2(2):73-7.
  • 12. Hasi G, Wu L, Sodnompil T, Yi R, Wu R, Zhang R, et al.. Differential expression and localisation of heat shock protein 70 (HSP70) and glutathione peroxidase 5 (GPX5) in the testis and epididymis of Sonid Bactrian camels. Reprod Fertil Dev 2023; 35(10):552-562.
  • 13. WHO TEAM: Sexual and Reproductive Health and Research. Infertility Prevalence Estimates, 1990–2021 (WHO, 2023).
  • 14. Thonneau P, Marchand S, Tallec A, Ferial ML, Ducot B, Lansac J, et al. Incidence and main causes of infertility in a resident population (1,850,000) of three French regions (1988-1989). Hum Reprod 1991; 6(6):811-6.
  • 15. Agarwal A, Mulgund A, Hamada A, Chyatte MR. A unique view on male infertility around the globe. Reprod Biol Endocrinol 2015; 13:37.
  • 16. Eisenberg ML, Esteves SC, Lamb DJ, Hotaling JM, Giwercman A, Hwang K, et al. Male infertility. Nat Rev Dis Primers 2023; 9(1):49.
  • 17. Kaltsas A. Oxidative Stress and Male Infertility: The Protective Role of Antioxidants. Medicina (Kaunas). 2023; 59(10):1769.
  • 18. O'Flaherty C. Reactive Oxygen Species and Male Fertility. Antioxidants (Basel) 2020; 9(4):287.
  • 19. Tapısız ÖL, Altınbaş SK, Abike F, Göktolga Ü. Jinekolog gözü ile semen analizi ve son gelişmeler. Turk J Obstet Gynecol 2012;1(9);25-31.
  • 20. Schlegel PN, Sigman M, Collura B, De Jonge CJ, Eisenberg ML, Lamb DJ, et al. Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline Part I. J Urol 2021;205(1):36-43.
  • 21. Dohle GR, Smit M, Weber RF. Androgens and male fertility. World J Urol 2003; 21(5):341-5.
  • 22. Khodamoradi K, Parmar M, Khosravizadeh Z, Kuchakulla M, Manoharan M, Arora H. The role of leptin and obesity on male infertility. Curr Opin Urol 2020; 30(3):334-339.
  • 23. Coviello AD, Matsumoto AM, Bremner WJ, Herbst KL, Amory JK, Anawalt BD, et al. Lowdose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression. J Clin Endocrinol Metab 2005; 90(5):2595-602.
  • 24. Jarow JP, Chen H, Rosner TW, Trentacoste S, Zirkin BR. Assessment of the androgen environment within the human testis: minimally invasive method to obtain intratesticular fluid. J Androl 2001; 22(4):640-5.
  • 25. Emmanuel M, Bokor BR. Tanner Stages. 2022. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 – ID: NBK470280.
  • 26. de Kretser DM. Editorial: Is spermatogenic damage associated with Leydig cell dysfunction? J Clin Endocrinol Metab 2004;89(7):3158-60.
  • 27. Koukkou E, Billa E, Kapolla N, Pappa A, Venaki E, Andreou L, et al. An empiric treatment for idiopathic oligozoospermia revisited: a 20-year investigative saga. Andrologia 2012; 44(5):337-42.
  • 28. Kontaş T, Ergün N, Turunç V. Isı şok proteinler ve fizyolojik rolleri. Kafkas Üniv Vet Fak Derg 2007; 13 (1): 109-114.
  • 29. Volloch VZ, Sherman MY. Oncogenic potential of Hsp72. Oncogene 1999;18(24):3648-51.
  • 30. Ferlin A, Speltra E, Patassini C, Pati MA, Garolla A, Caretta N, et al. Heat shock protein and heat shock factor expression in sperm: relation to oligozoospermia and varicocele. J Urol 2010; 183(3):1248-52.
  • 31. Dangi SS, Gupta M, Maurya D, Yadav VP, Panda RP, Singh G, et al. Expression profile of HSP genes during different seasons in goats (Capra hircus). Trop Anim Health Prod 2012; 44(8):1905-12.
  • 32. Chung L, Ng YC. Age-related alterations in expression of apoptosis regulatory proteins and heat shock proteins in rat skeletal muscle. Biochim Biophys Acta 2006; 1762(1):103-9.
  • 33. Jannatifar R, Cheraghi E, Nasr-Esfahani MH, Piroozmanesh H. Association of heat shock protein A2 expression and sperm quality after N-acetyl-cysteine supplementation in asthenoterato-zoospermic infertile men. Andrologia 2021; 53(5):e14024.
  • 34. Spinaci M, Volpe S, Bernardini C, De Ambrogi M, Tamanini C, Seren E, et al. Immunolocalization of heat shock protein 70 (Hsp 70) in boar spermatozoa and its role during fertilization. Mol Reprod Dev 2005; 72(4):534-41.
  • 35. Erata GO, Koçak Toker N, Durlanik O, Kadioğlu A, Aktan G, Aykaç Toker G. The role of heat shock protein 70 (Hsp 70) in male infertility: is it a line of defense against sperm DNA fragmentation? Fertil Steril 2008;90(2):322-7.
  • 36. Bak CW, Song SH, Yoon TK, Lim JJ, Shin TE, Sung S. Natural course of idiopathic oligozoospermia: comparison of mild, moderate and severe forms. Int J Urol 2010; 17(11):937-43.
  • 37. Yin Y, Cao S, Fu H, Fan X, Xiong J, Huang Q, et al. A noncanonical role of NOD-like receptor NLRP14 in PGCLC differentiation and spermatogenesis. Proc Natl Acad Sci USA 2020; 117(36):22237-48.
There are 37 citations in total.

Details

Primary Language English
Subjects Histology and Embryology
Journal Section Research Article
Authors

Ayla İzmitli 0009-0001-7476-1887

Esra Önal 0000-0002-2631-6033

Menekşe Ülger 0000-0003-0108-7948

Derya Karabulut 0000-0003-2067-6174

Ercan Mustafa Aygen 0000-0002-8677-0940

Birkan Yakan 0000-0002-5456-4579

Project Number yok
Early Pub Date July 5, 2025
Publication Date July 29, 2025
Submission Date February 27, 2025
Acceptance Date May 28, 2025
Published in Issue Year 2025 Volume: 6 Issue: 2

Cite

Vancouver İzmitli A, Önal E, Ülger M, Karabulut D, Aygen EM, Yakan B. Alterations in Heat Shock Protein 70 (Hsp70) Expression in Sperm of Individuals with Oligozoospermia and Severe Oligozoospermia. Exp Appl Med Sci. 2025;6(2):160-72.

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