https://doi.org/10.4081/aiua.2023.11502

Does isotretinoin affect spermatogenesis in the long term? A rat model

Vol. 95 No. 3 (2023)
Submitted: May 31, 2023
Accepted: June 8, 2023
Published: July 25, 2023
Isotretinoin, Rat, Spermatogenesis, Testis
Abstract Views: 942
PDF: 376
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Authors

Abdullah Cirakoglu
Ordu University, Faculty of Medicine, Urology Department, Ordu, Turkey.
Sevda Onder
Ordu University, Faculty of Medicine, Dermatology Department, Ordu, Turkey.
Hatice Hancı
Ordu University, Faculty of Medicine, Histology and Embriyology, Ordu, Turkey.
Erdal Benli
Ordu University, Faculty of Medicine, Urology Department, Ordu, Turkey.
Ahmet Yüce
ahmetyuce7@gmail.com
https://orcid.org/0000-0003-2931-3927
Ordu University, Faculty of Medicine, Urology Department, Ordu, Turkey.
Yeliz Kasko Arici
https://orcid.org/0000-0001-6820-0381
Ordu University, Faculty of Medicine, Biostatistics Department, Ordu, Turkey.
Orhan Bas
Samsun University, Faculty of Medicine, Anatomy Department, Samsun, Turkey.
Ismail Nalbant
Lokman Hekim University, Faculty of Medicine, Urology Department Ankara, Turkey.

Objectives: Spermatogenesis, in which cell regeneration continues, can be affected by environmental, chemical, psychological factors or various diseases. There is conflicting information in the literature about the effect of isotretinoin, which is widely used in acne treatment, on testes and spermatogenesis. Therefore, we planned a rat study to evaluate the long-term efficacy of oral isotretinoin on testicular tissues and spermatogenesis. Materials and methods: The Group 1 (n = 6) 7.5 mg/kg/day and the Group 2 (n = 6) received isotretinoin at a dose of 30 mg/kg/day dissolved in sunflower oil, the Sham Group (n = 6) received only sunflower oil by gavage, and the control group (n = 6) received standard feed and water for four weeks. After the 4th week, all animals were fed with standard feed and water and followed for the next four weeks. At the end of the 8th week, all animals were sacrificed under deep anesthesia. Seminiferous tubule diameters, epithelial thickness, apoptotic index, sperm number and motility recorded Results: Sperm count, motility, vitality, diameter of seminiferous tubule and germinal epithelium thickness were decreased and apoptotic index increased in the groups received isotretinoin. There was no significant difference between the groups in terms of testosterone levels. Conclusions: We consider that further comprehensive studies, including human clinical trials, should be conducted to examine the negative effects of isotretinoin on spermatogenesis in the long term especially when there is a need using isotretinoin in men for various reasons and to eliminate the contradictions in the literature in this regard.

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Crossref
Scopus
Google Scholar
Europe PMC
Zouboulis CC, Bettoli V. Management of severe acne. Br J Dermatol. 2015; 172:27-36. DOI: https://doi.org/10.1111/bjd.13639
Henry D, Dormuth C, Winquist B, et al. Occurrence of pregnancy and pregnancy outcomes during isotretinoin therapy. CMAJ. 2016; 188:723-730. DOI: https://doi.org/10.1503/cmaj.151243
Sankako MK, Garcia PC, Piffer RC, et al. Possible mechanism by which zinc protects the testicular function of rats exposed to cigarette smoke. Pharmacol Rep. 2012; 64:1537-1546. DOI: https://doi.org/10.1016/S1734-1140(12)70951-9
Hancı H, Odacı E, Kaya H, et al. The effect of prenatal exposure to 900-MHz electromagnetic field on the 21-old-day rat testicle. Reprod Toxicol. 2013; 42:203-209. DOI: https://doi.org/10.1016/j.reprotox.2013.09.006
Shahada OO, Kurdi AS, Aljawi AF, et al. Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis Syndrome Diagnosis in Adolescent and Isotretinoin as a Possible Serious Exacerbating Factor. Cureus. 2022; 14:e22776. DOI: https://doi.org/10.7759/cureus.22776
Motamedi M, Chehade A, Sanghera R, Grewal P. A Clinician's Guide to Topical Retinoids. J Cutan Med Surg. 2022; 26:71-78. DOI: https://doi.org/10.1177/12034754211035091
Mehra T, Borelli C, Burgdorf W, et al. Treatment of severe acne with low-dose isotretinoin. Acta Derm Venereol. 2012; 92:247-248. DOI: https://doi.org/10.2340/00015555-1325
Aksoy H, Cinar L, Acmaz G, et al. The effect of isotretinoin on ovarian reserve based on hormonal parameters, ovarian volume, and antral follicle count in women with acne. Gynecol Obstet Invest. 2015; 79:78-82. DOI: https://doi.org/10.1159/000371551
Sadek IA, Abdul-Mohsen MH. Long-term administration of vitamin A and the process of spermatogenesis. East Mediterr Health J. 1999; 5:123-129. DOI: https://doi.org/10.26719/1999.5.1.123
Livera G, Rouiller-Fabre V, Pairault C, et al. Regulation and perturbation of testicular functions by vitamin A. Reproduction. 2002; 124:173-180. DOI: https://doi.org/10.1530/rep.0.1240173
Çinar L, Kartal D, Ergin C, et al. The effect of systemic isotretinoin on male fertility. Cutan Ocul Toxicol. 2016; 35:296-299. DOI: https://doi.org/10.3109/15569527.2015.1119839
Amory JK, Ostrowski KA, Gannon JR, et al. Isotretinoin administration improves sperm production in men with infertility from oligoasthenozoospermia: a pilot study. Andrology. 2017; 5:1115-1123. DOI: https://doi.org/10.1111/andr.12420
Parsch EM, Ruzicka T, Przybilla B, Schill WB. Andrological investigations in men treated with acitretin (Ro 10-1670). Andrologia. 1990; 22:479-482. DOI: https://doi.org/10.1111/j.1439-0272.1990.tb02034.x
Török L, Kádár L, Kása M. Spermatological investigations in patients treated with etretinate and isotretinoin. Andrologia. 1987; 19:629-633. DOI: https://doi.org/10.1111/j.1439-0272.1987.tb01915.x
Hui Liu, Jie Li, Li Yu. Effects of acitretin on semen quality and reproductive hormone levels in patients with psoriasis vulgaris. Dermatologica Sinica. 2017; 35:55-58. DOI: https://doi.org/10.1016/j.dsi.2016.10.005
Onder S, Çırakog˘lu A, Nalbant I, et al. Does isotretinoin affect spermatogenesis? a rat study. Egypt J Dermatol Venerol. 2021; 41:75-82. DOI: https://doi.org/10.4103/ejdv.ejdv_20_20
Sengör B, Bayramgürler D, Müezzinoglu B, et al. Effects of acitretin on spermatogenesis of rats. J Eur Acad Dermatol Venereol. 2006; 20:689-692. DOI: https://doi.org/10.1111/j.1468-3083.2006.01573.x
Cai L, Hales BF, Robaire B. Induction of apoptosis in the germ cells of adult male rats after exposure to cyclophosphamide. Biol Reprod. 1997; 56:1490-1497. DOI: https://doi.org/10.1095/biolreprod56.6.1490
Print CG, Loveland KL. Germ cell suicide: new insights into apoptosis during spermatogenesis. Bioessays. 2000; 22:423-430. DOI: https://doi.org/10.1002/(SICI)1521-1878(200005)22:5<423::AID-BIES4>3.0.CO;2-0
Lin WW, Lamb DJ, Wheeler TM, et al. In situ end-labeling of human testicular tissue demonstrates increased apoptosis in conditions of abnormal spermatogenesis. Fertil Steril. 1997; 68:1065-1069. DOI: https://doi.org/10.1016/S0015-0282(97)00372-5
Høst E, Lindenberg S, Ernst E, Christensen F. DNA strand breaks in human spermatozoa: a possible factor, to be considered in couples suffering from unexplained infertility. Acta Obstet Gynecol Scand. 1999; 78:622-625. DOI: https://doi.org/10.1080/j.1600-0412.1999.780710.x
Karadag AS, Ertugrul DT, Tutal E, Akin KO. Isotretinoin influences pituitary hormone levels in acne patients. Acta Derm Venereol. 2011; 91:31-34. DOI: https://doi.org/10.2340/00015555-1013
Altucci L, Gronemeyer H. The promise of retinoids to fight against cancer. Nat Rev Cancer. 2001; 1:181-193. DOI: https://doi.org/10.1038/35106036
Gencoglan G, Tosun M. Effects of isotretinoin on spermatogenesis of rats. Cutan Ocul Toxicol. 2011; 30:55-60. DOI: https://doi.org/10.3109/15569527.2010.521537
Ghasemnezhad R, Mohammadghasemi F, Faghani M, Bahadori MH. Oxytocin can decrease germ cells apoptotic index in testis under acute ischemia reperfusion in a rat model. Iran J Reprod Med. 2015; 13:283-290.
Kandirali E, Cayan S, Armagan A, et al. Does the testicular apoptotic index vary with serum gonadotropins and testicular histopathology in infertile men? Urol Int. 2009; 83:349-353. DOI: https://doi.org/10.1159/000241681
Wing TY, Christensen AK. Morphometric studies on rat seminiferous tubules. Am J Anat. 1982; 165:13-25. DOI: https://doi.org/10.1002/aja.1001650103
Udoumoh AF, Igwebuike UM, Okoye CN, et al. Assessment of age-related morphological changes in the testes of post-hatch light ecotype Nigerian indigenous chicken. Anat Histol Embryol. 2021; 50:459-466. DOI: https://doi.org/10.1111/ahe.12649
Mohammadnejad D, Abedelahi A, Soleimani-Rad J, et al. Degenerative effect of Cisplatin on testicular germinal epithelium. Adv Pharm Bull. 2012; 2:173-177.
Abou-haila A, Tulsiani DR. Signal transduction pathways that regulate sperm capacitation and the acrosome reaction. Arch Biochem Biophys. 2009; 485:72-81. DOI: https://doi.org/10.1016/j.abb.2009.02.003
Visconti PE, Westbrook VA, Chertihin O, et al. Novel signaling pathways involved in sperm acquisition of fertilizing capacity. J Reprod Immunol. 2002; 53:133-150. DOI: https://doi.org/10.1016/S0165-0378(01)00103-6
Pelit ES, Katı B, Akın Y, Yeni E. The impact of environmental stress factors on sperm. Androl Bul. 2017; 19:61-64. DOI: https://doi.org/10.24898/tandro.2017.76993
Nasr M, Abd-Allah H, Ahmed-Farid OAH, et al. A comparative study between curcumin and curcumin nanoemulsion on high-fat, high-fructose diet-induced impaired spermatogenesis in rats. J Pharm Pharmacol. 2022; 74:268-281. DOI: https://doi.org/10.1093/jpp/rgab172

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How to Cite

Cirakoglu, A., Onder, S., Hancı, H., Benli, E., Yüce A., Kasko Arici, Y., Bas, O., & Nalbant, I. (2023). Does isotretinoin affect spermatogenesis in the long term? A rat model. Archivio Italiano Di Urologia E Andrologia, 95(3). https://doi.org/10.4081/aiua.2023.11502
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