Animal modeling methods for oligospermia: A review

Dinesh Sharma , Nitesh Parsaila , Archana Navale , Sagar Shinde , Nishant Patidar , Prachi Nahar , Ajay Shelke , Nilay Solanki

Asian Pacific Journal of Reproduction ›› 2026, Vol. 15 ›› Issue (2) : 49 -56.

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Asian Pacific Journal of Reproduction ›› 2026, Vol. 15 ›› Issue (2) :49 -56. DOI: 10.4103/apjr.apjr_62_25
Review Article
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Animal modeling methods for oligospermia: A review
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Abstract

Oligospermia, characterized by a low sperm count in semen, is a major cause of male infertility and may result from various factors including infections, lifestyle choices, retrograde ejaculation, tumors, hormonal imbalances, drug treatments, and environmental exposures. Animal models play a crucial role in understanding its pathophysiology, identifying therapeutic targets, and evaluating potential treatments. The current review highlights experimental models used to induce oligospermia in laboratory animals, focusing on chemical, surgical, and radiation-based approaches. We review the reversible and irreversible methods commonly employed to study impaired spermatogenesis, along with the key endpoints used to assess testicular function and sperm quality. Standard housing and feeding conditions relevant to oligospermia research are also summarized to support reproducibility and methodological consistency in experimental designs.

Keywords

Oligospermia / Infertility / Cyclophosphamide / Cisplatin / Sperm count / Sperm morphology / Testosterone / Spermatogonia

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Dinesh Sharma, Nitesh Parsaila, Archana Navale, Sagar Shinde, Nishant Patidar, Prachi Nahar, Ajay Shelke, Nilay Solanki. Animal modeling methods for oligospermia: A review. Asian Pacific Journal of Reproduction, 2026, 15 (2) : 49-56 DOI:10.4103/apjr.apjr_62_25

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Conflict of interest statement

The authors declare that they have no competing interests regarding the publication of the data included in the manuscript.

Funding

This study did not receive any funding from any organization.

Authors’ contributions

Dinesh Sharma helped in conceptualization of the review and data compilation. Nitesh Parsaila contributed to literature search and initial draft writing. Archana Navale played a crucial role in supervision, data analysis and critical revision of the manuscript. Sagar Shinde reviewed experimental models and pharmacological interventions and contributed to the methodology section. Nishant Patidar and Prachi Nahar assisted in manuscript structuring, reference management, and proofreading. Ajay Shelke contributed to critical evaluation of pharmacological agents and editing the discussion section. Nilay Solanki helped in refining the introduction and conclusion and was involved in final review and approval of the manuscript.

Publisher’ s Note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

[1]

Murrell D, Biggers A. Oligospermia: Symptoms, causes, treatment, and more. [Online] Available from:https://www.healthline.com/health/mens-health/oligospermia [Accessed 14th March 2026].

[2]

Agarwal A, Baskaran S, Parekh N, Cho CL, Henkel R, Vij S, et al. Male infertility. Lancet 2021; 397(10271): 319-333.

[3]

Hoang-Thi AP, Dang-Thi AT, Phan-Van S, Nguyen-Ba T, Truong-Thi PL, Le-Minh T, et al. The impact of high ambient temperature on human sperm parameters: A meta-analysis. Iran J Public Health 2022; 51(4): 710-723.

[4]

Khosravi A, Hasani A, Behnam P, Piryaei A, Pirani M, Aliaghaei A, et al. An effective method for establishing animal models of azoospermia and oligospermia. Andrologia 2021; 53(7): e14095.

[5]

Ilkhani S, Moradi A, Aliaghaei A. Spatial arrangement of testicular cells disrupted by transient scrotal hyperthermia and subsequent impairment of spermatogenesis. Andrologia 2020; 52(9): e13664.

[6]

Kanter M, Aktas C, Erboga M. Heat stress decreases testicular germ cell proliferation and increases apoptosis in short term: An immunohistochemical and ultrastructural study. Toxicol Ind Health 2013; 29(2): 99-113.

[7]

Wang C, Cui YG, Wang XH. Transient scrotal hyperthermia and levonorgestrel enhance testosterone-induced spermatogenesis suppression in men through increased germ cell apoptosis. J Clin Endocrinol Metab 2007; 92(8): 3292-3304.

[8]

Zohni K, Zhang X, Tan SL, Chan P, Nagano MC. The efficiency of male fertility restoration is dependent on the recovery kinetics of spermatogonial stem cells after cytotoxic treatment with busulfan in mice. Hum Reprod 2012; 27(1): 44-53.

[9]

Pu R, Liu J, Zhang A. Modeling methods for busulfan-induced oligospermia and asthenozoospermia in mice: A systematic review and meta-analysis. J Assist Reprod Genet 2023; 40(1): 19-32.

[10]

Petersen PM, Hansen SW, Giwercman A, Rørth M, Skakkebaek NE. Dose-dependent impairment of testicular function in patients treated with cisplatin-based chemotherapy for germ cell cancer. Ann Oncol 1994; 5(4): 355-358.

[11]

Abdel-Latif R, Fathy M, Anwar HA, Naseem M, Dandekar T, Othman EM, et al. Cisplatin-induced reproductive toxicity and oxidative stress: Ameliorative effect of kinetin. Antioxidants (Basel) 2022; 11(5): 863.

[12]

Tchounwou PB, Dasari S, Noubissi FK, Ray P, Kumar S. Advances in our understanding of the molecular mechanisms of action of cisplatin in cancer therapy. J Exp Pharmacol 2021; 13: 303-328.

[13]

Qu N, Kuramasu M, Hirayanagi Y, Nagahori K, Hayashi S, Ogawa Y, et al. Gosha-Jinki-Gan recovers spermatogenesis in mice with busulfan-induced aspermatogenesis. Int J Mol Sci 2018; 19(9): 2606.

[14]

Kim SH, Lee IC, Baek HS, Moon C, Kim SH, Kim JC, et al. Protective effect of diallyl disulfide on cyclophosphamide-induced testicular toxicity in rats. Lab Anim Res 2013; 29(4): 204-211.

[15]

Ghobadi E, Moloudizargari M, Asghari MH, Abdollahi M. The mechanisms of cyclophosphamide-induced testicular toxicity and the protective agents. Expert Opin Drug Metab Toxicol 2016; 13(5): 525-536.

[16]

Selvakumar E, Prahalathan C, Sudharsan PT, Varalakshmi P. Chemoprotective effect of lipoic acid against cyclophosphamide-induced changes in the rat sperm. Toxicology 2006; 217(1): 71-78.

[17]

Masala A, Faedda R, Alagna S. Use of testosterone to prevent cyclophosphamide-induced azoospermia. Ann Intern Med 1997; 126(4): 292-295.

[18]

Fukushima T, Kato M, Adachi T. Effects of sulfasalazine on sperm acrosome reaction and gene expression in the male reproductive organs of rats. Toxicol Sci 2005; 85(1): 675-682.

[19]

Ommati MM, Heidari R, Jamshidzadeh A, Zamiri MJ, Sun Z, Sabouri S, et al. Dual effects of sulfasalazine on rat sperm characteristics, spermatogenesis, and steroidogenesis in two experimental models. Toxicol Lett 2018; 284: 46-55.

[20]

O'Moráin C, Smethurst P, Doré CJ, Levi AJ. Reversible male infertility due to sulphasalazine: Studies in man and rat. Gut 1984; 25(10): 10781084.

[21]

Grigg A. Effect of hydroxyurea on sperm count, motility and morphology in adult men with sickle cell or myeloproliferative disease. Intern Med J 2007; 37(3): 190-192.

[22]

Musialek MW, Rybaczek D. Hydroxyurea-The good, the bad and the ugly. Genes 2021; 12(7): 1096.

[23]

Fan X, Zhu Y, Wang N, Zhang B, Zhang C, Wang Y, et al. Therapeutic dose of hydroxyurea-induced synaptic abnormalities on the mouse spermatocyte. Front Physiol 2021; 12: 666339.

[24]

Abd-Elrazek AM, El-Dash HA, Said NI. The role of propolis against paclitaxel-induced oligospermia, sperm abnormality, oxidative stress and DNA damage in testes of male rats. Andrologia 2020; 52(1): e13394.

[25]

Al-Sarar AS, Abobakr Y, Bayoumi AE, Hussein HI, Al-Ghothemi M. Reproductive toxicity and histopathological changes induced by lambda-cyhalothrin in male mice. Environ Toxicol 2014; 29(7): 750-762.

[26]

Ben Abdallah F, Fetoui H, Zribi N, Fakhfakh F, Keskes L. Quercetin attenuates lambda-cyhalothrin-induced reproductive toxicity in male rats. Environ Toxicol 2011; 28(12): 673-680.

[27]

Settar A, Khaldoun H, Tarzaali D. Lambda cyhalothrin and chlorantraniliprole caused biochemical, histological and immunohistochemical alterations in male rabbit liver: Ameliorative effect of vitamins A, D, E, C mixture. Toxicology 2023; 487: 153464.

[28]

Sakr S, Badawy G. Protective effect of curcumin on monosodium glutamate-induced reproductive toxicity in male albino rats. Glob J Pharmacol 2013; 7(4): 416-422.

[29]

Shalan H, Ramadan Y. The possible protective role of selenium nanoparticles against gentamicin-induced toxicity in the testis of adult male albino rat: Histological and immunohistochemical study. Egypt J Histol 2023; 46(1): 105-116.

[30]

Das R, Ghosh S. Long term effects of monosodium glutamate on spermatogenesis following neonatal exposure in albino mice: A histological study. Nepal Med Coll J 2010; 12(3): 149-153.

[31]

Taha M, Elazab ST, Saati AA. Zamzam water ameliorates gentamicin-induced testicular toxicity in a rat model via targeting sperm parameters, oxidative insult, inflammation, apoptosis and pituitary-gonadal axis. Toxics 2022; 11(1): 2.

[32]

Razi M, Malekinejad H. Varicocele-induced infertility in animal models. Int J Fertil Steril 2015; 9(2): 141-149.

[33]

D'Souza UJ. Toxic effects of 5-fluorouracil on sperm count in Wistar rats. Malays J Med Sci 2003; 10(1): 43-45.

[34]

Silva RC, Britto DMC, Pereira WF, Brito-Melo GEA, Machado CT, Pedreira MM, et al. Effect of short- and medium-term toxicity of doxorubicin on spermatogenesis in adult Wistar rats. Reprod Biol 2018; 18(2): 169-176.

[35]

Loewen PC, Switala J, Triggs-Raine BL. Catalases HPI and HPII in Escherichia coli are induced independently. Arch Biochem Biophys 1985; 243(1): 144-149.

[36]

Rajfer J, Turner TT, Rivera F, Howards SS, Sikka SC. Inhibition of testicular testosterone biosynthesis following experimental varicocele in rats. Biol Reprod 1987; 36(4): 933-937.

[37]

Saypol DC, Howards SS, Turner TT, Miller ED Jr. Influence of surgically induced varicocele on testicular blood flow, temperature and histology in adult rats and dogs. J Clin Invest 1981; 68(1): 39-45.

[38]

Meistrich ML. Effects of chemotherapy and radiotherapy on spermatogenesis. Eur Urol 1993; 23(1): 136-142.

[39]

Azmoonfar R, Mirzaei F, Najafi M, Varkeshi M, Ghazikhanlousani K, Momeni S, et al. Radiation-induced testicular damage in mice: Protective effects of apigenin revealed by histopathological evaluation. Curr Radiopharm 2024; 17(3): 238-246.

[40]

Mayo Clinic. Low sperm count-Diagnosis and treatment. [Online] Available from:https://www.mayoclinic.org/diseases-conditions/low-sperm-count/diagnosis-treatment/drc-20374591[Accessed 14th March 2026].

[41]

Tangsrisakda N, Iamsaard S. Effect of ethanol on the changes in testicular protein expression in adult male rats. Andrologia 2020; 52(10): e13784.

[42]

Vaghela PB, Navale AM, Patel CB, Patidar N, Nahar PD, Patel F, et al. Protective effects of chia seeds and omega-3 fatty acid against cyclophosphamide-induced oligospermia in male Wistar rats: Potential risks of adverse drug interaction with chia seeds. Yale J Biol Med 2023; 96(4): 455-465.

[43]

Mortimer D. A technical note on the assessment of human sperm vitality using eosin-nigrosin staining. Reprod Biomed Online 2020; 40(6): 851855.

[44]

Dcunha R, Hussein RS, Ananda H. Current insights and latest updates in sperm motility and associated applications in assisted reproduction. Reprod Sci 2022; 29(1): 7-25.

[45]

Parsaila N, Navale AM, Shelke AB, Patidar N, Sharma D, Shinde S, et al. Protective effect of aqueous extract of Myrica esculenta against cyclophosphamide-induced spermatogenesis dysfunction in Wistar rats via antioxidant Signaling pathway. Toxicol Res (Camb) 2025; 14(6): tfaf173. doi: 10.1093/toxres/tfaf173.

[46]

Srivastava NK, Pande M. (eds.) Protocols in semen biology (comparing assays). 1st ed. Singapore: Springer Singapore; 2017.

[47]

Dieudonné O, Godin PA, Van-Langendonckt A, Jamart J, Galanti L. Biochemical analysis of sperm and infertility. Clin Chem Lab Med 2001; 39(5): 455-457.

[48]

Alahmar AT. Role of oxidative stress in male infertility: An updated review. J Hum Reprod Sci 2019; 12(1): 4-18.

[49]

Goldblith SA, Proctor BE. Photometric determination of catalase activity. J Biol Chem 1950; 187(2): 705-709.

[50]

Rahman I, Kode A, Biswas SK. Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method. Nat Protoc 2006; 1(6): 3159-3165.

[51]

Iwase T, Tajima A, Sugimoto S. A simple assay for measuring catalase activity: A visual approach. Sci Rep 2013; 3: 3081.

[52]

Lushchak VI. Glutathione homeostasis and functions: Potential targets for medical interventions. J Amino Acids 2012; 2012: 736837.

[53]

Jîtcâ G, Fogarasi E, Osz BE. Profiling the concentration of reduced and oxidized glutathione in rat brain using HPLC/DAD chromatographic system. Molecules 2021; 26(21): 6590.

[54]

Mindnich R, Haller F, Halbach F, Moeller G, Hrabé de Angelis M, Adamski J, et al. Androgen metabolism via 17β-hydroxysteroid dehydrogenase type 3 in mammalian and non-mammalian vertebrates: Comparison of the human and the zebrafish enzyme. J Mol Endocrinol 2005; 35(2): 305-316.

[55]

Mohamed RH, Karam RA, Hagrass HA, Amer MG, Abd El-Haleem MR. Anti-apoptotic effect of spermatogonial stem cells on doxorubicin-induced testicular toxicity in rats. Gene 2015; 561(1): 107-114.

[56]

Yazawa T, Imamichi Y, Uwada J. Evaluation of 17β-hydroxysteroid dehydrogenase activity using androgen receptor-mediated transactivation. J Steroid Biochem Mol Biol 2020; 196: 105493.

[57]

Ricci G, Perticarari S, Fragonas E. Apoptosis in human sperm: Its correlation with semen quality and the presence of leukocytes. Hum Reprod 2002; 17(10): 2665-2672.

[58]

Bhattacharya I, Dey S, Banerjee A. Revisiting the gonadotropic regulation of mammalian spermatogenesis: Evolving lessons during the past decade. Front Endocrinol (Lausanne) 2023; 14: 1110572.

[59]

Agarwal A, Sharma RK, Gupta S, Boitrelle F, Finelli R, Parekh N, et al. Sperm vitality and necrozoospermia: Diagnosis, management and results of a global survey of clinical practice. World J Mens Health 2022; 40(2): 228-242.

[60]

Lachaud C. Apoptosis and necrosis in human ejaculated spermatozoa. Hum Reprod 2004; 19(3): 607-610.

[61]

García Fernández JM, Cajigal D, López-Fernández C, Gosálvez J. Assessing sperm DNA fragmentation with the sperm chromatin dispersion test. Methods Mol Biol 2011; 682: 291-301.

[62]

Fernández JL, Muriel L, Rivero MT, Goyanes V, Vazquez R, Alvarez JG. The sperm chromatin dispersion test: A simple method for the determination of sperm DNA fragmentation. J Androl 2003; 24(1): 59-66.

[63]

Kyrylkova K, Kyryachenko S, Leid M, Kioussi C. Detection of apoptosis by TUNEL assay. Methods Mol Biol 2012; 887: 41-47.

[64]

Olive PL, Banáth JP. The comet assay: A method to measure DNA damage in individual cells. Nat Protoc 2006; 1(1): 23-29.

[65]

Zhao W, Jing J, Shao Y. Circulating sex hormone levels in relation to male sperm quality. BMC Urol 2020; 20(1): 101.

[66]

Firdous S, Begum Z, Patil S, Kauser SH. Correlation of parameters of semen analysis in oligospermia in infertility. Int J Health Med Res 2023; 2(4): 70-77.

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