Skip to main content
Log in

Elderberry Diet Restores Spermatogenesis in the Transient Scrotal Hyperthermia-Induced Mice

  • Reproductive Biology: Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Over the past years, several studies have also reported the adverse effects of hyperthermia on normal testicular tissues in several species including mice, rats, and humans. These deleterious impacts include temporarily drop in relative weight of testis along with a temporary partial or complete infertility. Sambucus nigra, also known as elderberry or sweet elder, is a source of bioactive compounds that has drawn growing attention for its potential beneficial effects in preventing and treating several diseases. This experimental research divided 30 mice into the following three groups: (1) control, (2) hyperthermia, and (3) hyperthermia receiving elderberry diet for 35 days. Scrotal hyperthermia was induced by water bath with 43 °C for 30 min. Then, the mice were euthanized, and their sperm samples were collected for sperm parameters analysis. Then, we took the testis samples for histopathological experimentations, immunohistochemistry against TNF-α and caspase-3 and serum testosterone, FSH and LH levels. Our outputs indicated that elderberry diet could largely improve the sperms parameters and stereological parameters, like spermatogonia, primary spermatocyte, round spermatid, and Leydig cells together with an increasing level of the serum testosterone compared to the scrotal hyperthermia induced mice. In addition, it was found that the expression of TNF-α and caspase-3 significantly decreased in the treatment groups by elderberry diet compared to the scrotal hyperthermia-induced mice. In conclusion, it could be concluded that elderberry diet may be regarded as an alternative treatment for improving the spermatogenesis process in the scrotal hyperthermia induced mice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Data Availability

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

References

  1. Costa AGV, Garcia-Diaz DF, Jimenez P, Silva PI. Bioactive compounds and health benefits of exotic tropical red–black berries. J Funct Foods. 2013;5(2):539–49.

    Article  CAS  Google Scholar 

  2. Sidor A, Gramza-Michałowska A. Advanced research on the antioxidant and health benefit of elderberry (Sambucus nigra) in food–a review. J Funct Foods. 2015;18:941–58.

    Article  CAS  Google Scholar 

  3. Abdramanov A, Massanyi P, Sarsembayeva N, Usenbayev A, Alimov J, Tvrdá E. The in vitro effect of elderberry (Sambucus nigra) extract on the activity and oxidative profile of bovine spermatozoa. J Microbiol Biotechnol Food Sci. 2020;9(5):1319–22.

    Google Scholar 

  4. Kaur K, Kaur R, Kaur H, Kaur S. A comprehensive review: Sambucus nigra. Linn Biolife. 2014;2(3):941–8.

    Google Scholar 

  5. Demo A, Petrakis C, Kefalas P, Boskou D. Nutrient antioxidants in some herbs and Mediterranean plant leaves. Food Res Int. 1998;31(5):351–4.

    Article  Google Scholar 

  6. Sánchez-Moreno C, Larrauri JA, Saura-Calixto F. Free radical scavenging capacity and inhibition of lipid oxidation of wines, grape juices and related polyphenolic constituents. Food Res Int. 1999;32(6):407–12.

    Article  Google Scholar 

  7. Dawidowicz AL, Wianowska D, Baraniak B. The antioxidant properties of alcoholic extracts from Sambucus nigra L.(antioxidant properties of extracts). LWT. 2006;39(3):308–15.

    Article  CAS  Google Scholar 

  8. David L, Moldovan B, Vulcu A, Olenic L, Perde-Schrepler M, Fischer-Fodor E, et al. Green synthesis, characterization and anti-inflammatory activity of silver nanoparticles using European black elderberry fruits extract. Colloids Surf B. 2014;122:767–77.

    Article  CAS  Google Scholar 

  9. Duymuş HG, Göger F, Başer KHC. In vitro antioxidant properties and anthocyanin compositions of elderberry extracts. Food Chem. 2014;155:112–9.

    Article  Google Scholar 

  10. Harokopakis E, Albzreh MH, Haase EM, Scannapieco FA, Hajishengallis G. Inhibition of proinflammatory activities of major periodontal pathogens by aqueous extracts from elder flower (Sambucus nigra). J Periodontol. 2006;77(2):271–9.

    Article  Google Scholar 

  11. Porter RS, Bode RF. A review of the antiviral properties of black elder (Sambucus nigra L.) products. Phytother Res. 2017;31(4):533–54.

    Article  Google Scholar 

  12. Lin P, Hwang E, Ngo HT, Seo SA, Yi T-H. Sambucus nigra L. ameliorates UVB-induced photoaging and inflammatory response in human skin keratinocytes. Cytotechnology. 2019;71(5):1003–17.

    Article  CAS  Google Scholar 

  13. Shahidi F, Janitha P, Wanasundara P. Phenolic antioxidants. Crit Rev Food Sci Nutr. 1992;32(1):67–103.

    Article  CAS  Google Scholar 

  14. Jovanovic SV, Steenken S, Tosic M, Marjanovic B, Simic MG. Flavonoids as antioxidants. J Am Chem Soc. 1994;116(11):4846–51.

    Article  CAS  Google Scholar 

  15. Vinson JA, Dabbagh YA, Serry MM, Jang J. Plant flavonoids, especially tea flavonols, are powerful antioxidants using an in vitro oxidation model for heart disease. J Agric Food Chem. 1995;43(11):2800–2.

    Article  CAS  Google Scholar 

  16. Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med. 1996;20(7):933–56.

    Article  CAS  Google Scholar 

  17. Cao G, Sofic E, Prior RL. Antioxidant and prooxidant behavior of flavonoids: structure-activity relationships. Free Radic Biol Med. 1997;22(5):749–60.

    Article  CAS  Google Scholar 

  18. Brown EJ, Khodr H, Hider CR, Rice-Evans CA. Structural dependence of flavonoid interactions with Cu2+ ions: implications for their antioxidant properties. Biochem J. 1998;330(3):1173–8.

    Article  CAS  Google Scholar 

  19. Paganga G, Miller N, Rice-Evans CA. The polyphenolic content of fruit and vegetables and their antioxidant activities. What does a serving constitute? Free Radic Res. 1999;30(2):153–62.

    Article  CAS  Google Scholar 

  20. D’cruz SC, Vaithinathan S, Jubendradass R, Mathur PP. Effects of plants and plant products on the testis. Asian J Androl. 2010;12(4):468.

    Article  Google Scholar 

  21. Moore CR. Heat application and testicular degeneration. Anat Rec. 1923;26:344–5.

    Google Scholar 

  22. Hand J, Walker H, Hornsey S, Field S. Effects of hyperthermia on the mouse testis and its response to X-rays, as assayed by weight loss. Int J Radiat Biol. 1979;35(6):521–8.

    CAS  Google Scholar 

  23. Collins P, Lacy D. Studies on the structure and function of the mammalian testis. II. Cytological and histochemical observations on the testis of the rat after a single exposure to heat applied for different lengths of time. Proc Royal Soc B. 1969;172(1026):17–38.

    CAS  Google Scholar 

  24. Baranski B. Effects of the workplace on fertility and related reproductive outcomes. Environ Health Perspect. 1993;101(suppl 2):81–90.

    Article  Google Scholar 

  25. Mieusset R, Bujan L. Testicular heating and its possible contributions to male infertility: a review. Int j androl. 1995;18(4):169–84.

    Article  CAS  Google Scholar 

  26. Jannes P, Spiessens C, Van Der Auwera I, D’Hooghe T, Verhoeven G, Vanderschueren D. Male subfertility induced by acute scrotal heating affects embryo quality in normal female mice. Hum Reprod. 1998;13(2):372–5.

    Article  CAS  Google Scholar 

  27. Setchell B, D’occhio M, Hall M, Laurie M, Tucker M, Zupp J. Is embryonic mortality increased in normal female rats mated to subfertile males? Reproduction. 1988;82(2):567–74.

    Article  CAS  Google Scholar 

  28. Setchell B, Ekpe G, Zupp J, Surani M. Transient retardation in embryo growth in normal female mice made pregnant by males whose testes had been heated. Hum Reprod. 1998;13(2):342–7.

    Article  CAS  Google Scholar 

  29. Sharma R, Goyal A, Bhat R. Antifertility activity of plants extracts on female reproduction: a review. Int J Pharma Bio Sci. 2013;3(3):493–514.

    Google Scholar 

  30. Lee J, Durst RW, Wrolstad RE, Kupina Cetgmhjhhkskd JD, Smsmbmtpfrasgtuw. Determination of total monomeric anthocyanin pigment content of fruit juices, beverages, natural colorants, and wines by the pH differential method: collaborative study. Journal of AOAC international. 2005;88(5):1269–78.

    Article  CAS  Google Scholar 

  31. Ziaeipour S, Rezaei F, Piryaei A, Abdi S, Moradi A, Ghasemi A, et al. Hyperthermia versus busulfan: Finding the effective method in animal model of azoospermia induction. Andrologia. 2019;51(11):e13438.

    Article  Google Scholar 

  32. Zarei L, Sadrkhanlou R, Shahrooz R, Malekinejad H, Eilkhanizadeh B, Ahmadi A, editors. Protective effects of vitamin E and Cornus mas fruit extract on methotrexate-induced cytotoxicity in sperms of adult mice. Vet Res Forum. 2014;5(1):21–7.

  33. Panahi S, Karamian A, Sajadi E, Aliaghaei A, Nazarian H, Abdi S, et al. Sertoli cell–conditioned medium restores spermatogenesis in azoospermic mouse testis. Cell Tissue Res. 2020;379(3):577–87.

    Article  CAS  Google Scholar 

  34. Ziaeipour S, Ahrabi B, Naserzadeh P, Aliaghaei A, Sajadi E, Abbaszadeh H-A, et al. Effects of Sertoli cell transplantation on spermatogenesis in azoospermic mice. Cell Physiol Biochem. 2019;52:421–34.

    Article  CAS  Google Scholar 

  35. Velioglu Y, Mazza G, Gao L, Oomah B. Antioxidant activity and total phenolics in selected fruits, vegetables, and grain products. J Agric Food Chem. 1998;46(10):4113–7.

    Article  CAS  Google Scholar 

  36. Wang H, Cao G, Prior RL. Total antioxidant capacity of fruits. J Agric Food Chem. 1996;44(3):701–5.

    Article  CAS  Google Scholar 

  37. Moyer RA, Hummer KE, Finn CE, Frei B, Wrolstad RE. Anthocyanins, phenolics, and antioxidant capacity in diverse small fruits: Vaccinium, Rubus, and Ribes. J Agric Food Chem. 2002;50(3):519–25.

    Article  CAS  Google Scholar 

  38. Kende H. Biochemistry and molecular biology of plants. Science. 2000;290(5492):719.

    Article  CAS  Google Scholar 

  39. Kaur C, Kapoor HC. Antioxidants in fruits and vegetables–the millennium’s health. Int J Food Sci Technol. 2001;36(7):703–25.

    Article  CAS  Google Scholar 

  40. Prior R. Absorption and metabolism of anthocyanins: potential health effects. Phytochemicals: Mechanisms of action. In: Meskin, M.S., Bidlack, W.R., Davies, A.J. editors. Phytochemiclas: Mechanisms of Action. 1st Edition. Boca Raton, FL: CRC Press. 2004;1–19.

  41. Zafra-Stone S, Yasmin T, Bagchi M, Chatterjee A, Vinson JA, Bagchi D. Berry anthocyanins as novel antioxidants in human health and disease prevention. Mol Nutr Food Res. 2007;51(6):675–83.

    Article  CAS  Google Scholar 

  42. Sun J, Chu YF, Wu X, Liu RH. Antioxidant and antiproliferative activities of common fruits. J Agric Food Chem. 2002;50(25):7449–54.

  43. Koca I, Karadeniz B. Antioxidant properties of blackberry and blueberry fruits grown in the Black Sea Region of Turkey. Sci Hortic. 2009;121(4):447–50.

    Article  CAS  Google Scholar 

  44. Lee J, Finn CE. Anthocyanins and other polyphenolics in American elderberry (Sambucus canadensis) and European elderberry (S. nigra) cultivars. Journal of the Science of Food and Agriculture. 2007;87(14):2665–75.

    Article  CAS  Google Scholar 

  45. Akbulut M, Ercisli S, Tosun M. Physico-chemical characteristics of some wild grown European elderberry (Sambucus nigra L.) genotypes. Pharmacognosy magazine. 2009;5(20):320.

    Article  Google Scholar 

  46. Özgen M, Scheerens JC, Reese RN, Miller RA. Total phenolic, anthocyanin contents and antioxidant capacity of selected elderberry (Sambucus canadensis L.) accessions. Pharmacognosy magazine. 2010;6(23):198.

    Article  Google Scholar 

  47. Johnson MC, Thomas AL, Greenlief CM. Impact of frozen storage on the anthocyanin and polyphenol contents of American elderberry fruit juice. J Agric Food Chem. 2015;63(23):5653–9.

    Article  CAS  Google Scholar 

  48. Ramesh P, Okigbo R. Effects of plants and medicinal plant combinations as anti-infectives. Afr J Pharm Pharmacol. 2008;2(7):130–5.

    Google Scholar 

  49. Omogbadegun Z, Uwadia C, Ayo C, Mbarika V, Omoregbe N, Otofia E, et al. Multimedia-based medicinal plants sustainability management system. International Journal of Computer Science Issues. 2011.

  50. Tohamy AA, Ibrahim SR, Moneim AEA. Studies on the effect of Salvia aegyptiaca and Trigonella foenum graecum extracts on adult male mice. J Appl Pharm Sci. 2012;2(5):36.

    Article  Google Scholar 

  51. Hamidpour M, Hamidpour R, Hamidpour S, Shahlari M. Chemistry, pharmacology, and medicinal property of sage (Salvia) to prevent and cure illnesses such as obesity, diabetes, depression, dementia, lupus, autism, heart disease, and cancer. J Tradit Complement Med. 2014;4(2):82–8.

    Article  Google Scholar 

  52. Abdramanov A, Massanyi P, Sarsembayeva N, Usenbayev A, Alimov J, Tvrdá E. The in vitro effect of elderberry (Sambucus nigra) extract on the activity and oxidative profile of bovine spermatozoa. J Microbiol Biotechnol Food Sci. 2021;2021:1319–22.

    Google Scholar 

  53. Gramza-Michalowska A, Sidor A, Hes M. Herb extract influence on the oxidative stability of selected lipids. J Food Biochem. 2011;35(6):1723–36.

    Article  CAS  Google Scholar 

  54. Kmiecik D, Korczak J, Rudzińska M, Kobus-Cisowska J, Gramza-Michałowska A, Hęś M. β-Sitosterol and campesterol stabilisation by natural and synthetic antioxidants during heating. Food Chem. 2011;128(4):937–42.

    Article  CAS  Google Scholar 

  55. Kobus-Cisowska J, Flaczyk E, Rudzińska M, Kmiecik D. Antioxidant properties of extracts from Ginkgo biloba leaves in meatballs. Meat Sci. 2014;97(2):174–80.

    Article  CAS  Google Scholar 

  56. PB Gollucke A, C Peres R, A Jr O, A Ribeiro D. Polyphenols: a nutraceutical approach against diseases. Recent Pat food, Nutr Agric. 2013;5(3):214-9.

  57. Xiang Q, Wang Y, Wu W, Meng X, Qiao Y, Xu L, et al. Carnosic acid protects against ROS/RNS-induced protein damage and upregulates HO-1 expression in RAW264. 7 macrophages. J Funct Foods. 2013;5(1):362–9.

    Article  CAS  Google Scholar 

  58. Lee CY. Challenges in providing credible scientific evidence of health benefits of dietary polyphenols. J Funct Foods. 2013;1(5):524–6.

    Article  Google Scholar 

  59. Li Y. Antioxidants in biology and medicine: essentials, advances, and clinical applications: Edition, illustrated. Publishers, Nova Science. 2011;422.

  60. Ramos S, Rodríguez-Ramiro I, Martín MA, Goya L, Bravo L. Dietary flavanols exert different effects on antioxidant defenses and apoptosis/proliferation in Caco-2 and SW480 colon cancer cells. Toxicol In Vitro. 2011;25(8):1771–81.

    Article  CAS  Google Scholar 

  61. Martins TF, Palomino OM, Álvarez-Cilleros D, Martín MA, Ramos S, Goya L. Cocoa flavanols protect human endothelial cells from oxidative stress. Plant Foods Hum Nutr. 2020;75(2):161–8.

    Article  CAS  Google Scholar 

  62. Moura de Gouveia N, Ramos S, Martín MÁ, Espindola FS, Goya L, Palomino OM. Vochysia rufa stem bark extract protects endothelial cells against high glucose damage. Medicines. 2017;4(1):9.

    Article  Google Scholar 

  63. León-González AJ, Mateos R, Ramos S, Martín MÁ, Sarriá B, Martín-Cordero C, et al. Chemo-protective activity and characterization of phenolic extracts from Corema album. Food Res Int. 2012;49(2):728–38.

    Article  Google Scholar 

  64. Palomino OM, Gouveia NM, Ramos S, Martín MA, Goya L. Protective effect of Silybum marianum and Silibinin on endothelial cells submitted to high glucose concentration. Planta Med. 2017;83(01/02):97–103.

    CAS  Google Scholar 

  65. Martin MA, Ramos S, Mateos R, Marais JP, Bravo-Clemente L, Khoo C, et al. Chemical characterization and chemo-protective activity of cranberry phenolic powders in a model cell culture. Response of the antioxidant defenses and regulation of signaling pathways. Food research international. 2015;71:68–82.

    Article  CAS  Google Scholar 

  66. Baeza G, Amigo-Benavent M, Sarriá B, Goya L, Mateos R, Bravo L. Green coffee hydroxycinnamic acids but not caffeine protect human HepG2 cells against oxidative stress. Food Res Int. 2014;62:1038–46.

    Article  CAS  Google Scholar 

  67. Palomino O, García-Aguilar A, González A, Guillén C, Benito M, Goya L. Biological actions and molecular mechanisms of Sambucus nigra L. in neurodegeneration: a cell culture approach. Molecules. 2021;26(16):4829.

    Article  CAS  Google Scholar 

  68. Bagchi D, Roy S, Patel V, He G, Khanna S, Ojha N, et al. Safety and whole-body antioxidant potential of a novel anthocyanin-rich formulation of edible berries. Mol Cell Biochem. 2006;281(1):197–209.

    Article  CAS  Google Scholar 

  69. Opris R, Tatomir C, Olteanu D, Moldovan R, Moldovan B, David L, et al. The effect of Sambucus nigra L. extract and phytosinthesized gold nanoparticles on diabetic rats. Colloids and Surfaces B: Biointerfaces. 2017;150:192–200.

    Article  CAS  Google Scholar 

  70. Moghaddam MH, Bayat A-H, Eskandari N, Abdollahifar M-A, Fotouhi F, Forouzannia A, et al. Elderberry diet ameliorates motor function and prevents oxidative stress-induced cell death in rat models of Huntington disease. Brain Research. 2021;1762:147444.

    Article  CAS  Google Scholar 

  71. Lanzafame FM, La Vignera S, Vicari E, Calogero AE. Oxidative stress and medical antioxidant treatment in male infertility. Reprod Biomed Online. 2009;19(5):638–59.

    Article  CAS  Google Scholar 

  72. Tvrdá E, Kňažická Z, Bárdos L, Massányi P, Lukáč N. Impact of oxidative stress on male fertility—A review. Acta Vet Hung. 2011;59(4):465–84.

    Article  Google Scholar 

  73. Bansal AK, Bilaspuri G. Impacts of oxidative stress and antioxidants on semen functions. Vet Med Int. 2010;2010:686137.

  74. Gharagozloo P, Aitken RJ. The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy. Hum Reprod. 2011;26(7):1628–40.

    Article  Google Scholar 

  75. Butler A, He X, Gordon RE, Wu H-S, Gatt S, Schuchman EH. Reproductive pathology and sperm physiology in acid sphingomyelinase-deficient mice. Am J Pathol. 2002;161(3):1061–75.

    Article  CAS  Google Scholar 

  76. De Iuliis GN, Wingate JK, Koppers AJ, McLaughlin EA, Aitken RJ. Definitive evidence for the nonmitochondrial production of superoxide anion by human spermatozoa. J Clin Endocrinol Metab. 2006;91(5):1968–75.

    Article  Google Scholar 

  77. Tremellen K. Oxidative stress and male infertility—a clinical perspective. Hum Reprod Update. 2008;14(3):243–58.

    Article  CAS  Google Scholar 

  78. Aitken RJ, Baker MA, De Iuliis GN, Nixon B. New insights into sperm physiology and pathology. Handb Exp Pharmacol. 2010;(198):99–115.

  79. Allan D, Harmon B, Kerr J. Cell death in spermatogenesis. In: Potten CS, editor. perspectives on Mammalian Cell Death. New York & Tokyo: Oxford University Press, Oxford; 1987.

    Google Scholar 

  80. Bartke A. Apoptosis of male germ cells, a generalized or a cell type-specific phenomenon? Endocrinology. 1995;136(1):3–4.

    Article  CAS  Google Scholar 

  81. Mori C, Nakamura N, Dix DJ, Fujioka M, Nakagawa S, Shiota K, et al. Morphological analysis of germ cell apoptosis during postnatal testis development in normal and Hsp70-2 knockout mice. Dev Dyn. 1997;208(1):125–36.

    Article  CAS  Google Scholar 

  82. Rockett JC, Mapp FL, Garges JB, Luft JC, Mori C, Dix DJ. Effects of hyperthermia on spermatogenesis, apoptosis, gene expression, and fertility in adult male mice. Biol Reprod. 2001;65(1):229–39.

    Article  CAS  Google Scholar 

  83. Chowdhury A, Steinberger E. A quantitative study of the effect of heat on germinal epithelium of rat testes. Am J Anat. 1964;115(3):509–24.

    Article  CAS  Google Scholar 

  84. Mieusset R, Bujan L, Mondinat C, Mansat A, Pontonnier F, Grandjean H. Association of scrotal hyperthermia with impaired spermatogenesis in infertile men. Fertil Steril. 1987;48(6):1006–11.

    Article  CAS  Google Scholar 

  85. Khan VR, Brown IR. The effect of hyperthermia on the induction of cell death in brain, testis, and thymus of the adult and developing rat. Cell Stress Chaperones. 2002;7(1):73–90.

  86. Waites G, Setchell B. Physiology of the mammalian testis. Marshall’s physiology of reproduction. 1990;2:1–105.

    Google Scholar 

  87. Yin Y, Hawkins KL, Dewolf WC, Morgentaler A. Heat stress causes testicular germ cell apoptosis in adult mice. Journal of Andrology. 1997;18(2):159–65.

    CAS  Google Scholar 

  88. Blanco-Rodríguez J, Martínez-García C. Apoptosis pattern elicited by several apoptogenic agents on the seminiferous epithelium of the adult rat testis. J Androl. 1998;19(4):487–97.

    Google Scholar 

  89. Lue Y-H, Sinha Hikim AP, Swerdloff RS, Im P, Taing KS, Bui T, et al. Single exposure to heat induces stage-specific germ cell apoptosis in rats: role of intratesticular testosterone on stage specificity. Endocrinology. 1999;140(4):1709–17.

    Article  CAS  Google Scholar 

  90. Wildeus S, Entwistle K. Spermiogram and sperm reserves in hybrid Bos indicus× Bos taurus bulls after scrotal insulation. Reproduction. 1983;69(2):711–6.

    Article  CAS  Google Scholar 

  91. Kim B, Park K, Rhee K. Heat stress response of male germ cells. Cell Mol Life Sci. 2013;70(15):2623–36.

    Article  CAS  Google Scholar 

  92. Yin Y, Stahl BC, Dewolf WC, Morgentaler A. P53 and Fas are sequential mechanisms of testicular germ cell apoptosis. J Androl. 2002;23(1):64–70.

    Article  CAS  Google Scholar 

  93. Zielińska-Wasielica J, Olejnik A, Kowalska K, Olkowicz M, Dembczyński R. Elderberry (Sambucus nigra L.) fruit extract alleviates oxidative stress, insulin resistance, and inflammation in hypertrophied 3T3-L1 adipocytes and activated RAW 264.7 Macrophages. Foods. 2019;8(8):326.

    Article  Google Scholar 

  94. Aderem A, Ulevitch RJ. Toll-like receptors in the induction of the innate immune response. Nature. 2000;406(6797):782–7.

    Article  CAS  Google Scholar 

  95. Rodríguez-Hernández H, Simental-Mendía LE, Rodríguez-Ramírez G, Reyes-Romero MA. Obesity and inflammation: epidemiology, risk factors, and markers of inflammation. Int J Endocrinol. 2013;2013.

  96. Bozkaya F, Atli M, Guzeloglu A, Kayis S, Yildirim M, Kurar E, et al. Effects of long-term heat stress and dietary restriction on the expression of genes of steroidogenic pathway and small heat-shock proteins in rat testicular tissue. Andrologia. 2017;49(6):e12668.

    Article  Google Scholar 

  97. Mete F, Kilic E, Somay A, Yilmaz B. Effects of heat stress on endocrine functions & behaviour in the pre-pubertal rat. Indian J Med Res. 2012;135(2):233.

    Google Scholar 

  98. Rizzoto G, Ferreira J, Codognoto V, Oliveira K, García HM, Pupulim A, et al. Testicular hyperthermia reduces testosterone concentrations and alters gene expression in testes of Nelore bulls. Theriogenology. 2020;152:64–8.

    Article  CAS  Google Scholar 

  99. Shahat A, Rizzoto G, Kastelic J. Amelioration of heat stress-induced damage to testes and sperm quality. Theriogenology. 2020;158:84–96.

  100. O’Bryan M, Schlatt S, Gerdprasert O, Phillips DJ, de Kretser DM, Hedger MP. Biol reprod. 2000;63:1285–93.

    Article  CAS  Google Scholar 

  101. Liew SH, Meachem SJ, Hedger MP. A stereological analysis of the response of spermatogenesis to an acute inflammatory episode in adult rats. J Androl. 2007;28(1):176–85.

    Article  Google Scholar 

  102. Hedger MP. Immunophysiology and pathology of inflammation in the testis and epididymis. J Androl. 2011;32(6):625–40.

    Article  CAS  Google Scholar 

  103. O'Bryan MK, Hedger MP. Inflammatory networks in the control of spermatogenesis: chronic inflammation in an immunologically privileged tissue? Adv Exp Med Biol. 2008;636:92–114.

  104. Hedger MP. Toll-like receptors and signalling in spermatogenesis and testicular responses to inflammation—a perspective. J Reprod Immunol. 2011;88(2):130–41.

    Article  CAS  Google Scholar 

  105. Farrell NJ, Norris GH, Ryan J, Porter CM, Jiang C, Blesso CN. Black elderberry extract attenuates inflammation and metabolic dysfunction in diet-induced obese mice. Br J Nutr. 2015;114(8):1123–31.

    Article  CAS  Google Scholar 

  106. Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2018;9(6):7204.

    Article  Google Scholar 

  107. García-Alonso V, Titos E, Alcaraz-Quiles J, Rius B, Lopategi A, Lopez-Vicario C, et al. Prostaglandin E2 exerts multiple regulatory actions on human obese adipose tissue remodeling, inflammation, adaptive thermogenesis and lipolysis. PloS one. 2016;11(4):e0153751.

    Article  Google Scholar 

Download references

Acknowledgements

We are thankful for the funding provided by Student Research Committee, Shahid Beheshti University of Medical Sciences, and Tehran, Iran.

Funding

The study was funded by Men’s Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran (Registration number: 27615).

Author information

Authors and Affiliations

Authors

Contributions

AA and MAA designed and conceived the study; MHM and SF analyzed and interpreted the data, and revised the manuscript for intellectual contents; AH and AK wrote the manuscript; MP, KV, and MF revised the manuscript; NE, AG, and SS performed the experiments; KN had a crucial role in data collection and revised the manuscript and drafted the manuscript for the intellectual content.

Ethics declarations

Ethic Approval

The protocol of this study was reviewed and confirmed by Ethics Committee at Shahid Beheshti University of Medical Sciences (IR.SBMU.MSP.REC1400.023).

Competing Interests

The authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Moghaddam, M.H., Farrokhi, S., Hasani, A. et al. Elderberry Diet Restores Spermatogenesis in the Transient Scrotal Hyperthermia-Induced Mice. Reprod. Sci. 29, 3373–3386 (2022). https://doi.org/10.1007/s43032-022-00865-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-022-00865-7

Keywords

Navigation