Investigation the effect of isotretinoin on ovary tissues and reproduction in female rats
DOI:
https://doi.org/10.52783/jns.v14.3732Keywords:
Isotretinoin, acne vulgaris, ovaries, teratogenic agentAbstract
Background: Oral isotretinoin, a potent synthetic retinoid, derived from vitamin A, uniquely eradicates acne vulgaris. Its multifaceted action on skin health is attributed to nuclear and non-nuclear receptor transactivation. However, isotretinoin's teratogenicity and associated serious adverse effects necessitate careful consideration, particularly regarding its use during pregnancy, where a notable incidence of congenital anomalies and spontaneous abortion has been documented. Isotretinoin is regarded as a highly teratogenic agent. may adversely affect ovarian reserve and female fertility, evidenced by decreased anti-mullerian hormone (AMH) levels. .
Objective: This study aims to elucidate the detrimental effects of toxic isotretinoin doses on reproductive efficacy by investigating its influence on reproductive organs tissue and reproduction.
Materials and methods: forty rats were used in this study, The current study consists of two parts each part used 20 rats which lasted for month. each group contain 5 rats. The first part: Consists of four groups, The first group was the control group, while the second group was given the drug 15 mg/kg isotretinoin and the third group was given 30 mg/kg isotretinoin. The fourth group was given 30 mg/kg isotretinoin and omega-3 for 30 days. the blood samples of all rats were obtained by cardiac puncture under the anesthesia for Assessment of histopathological ovaries for Rat. Then, the rats were sacrificed, and bilateral ovariectomy was performed ovarian tissues were fixed in a 10% formalin solution for histological evaluation. It was noticed after a histological exam in groups 3, and 4 that the ovarian atrophied mucosal with degeneration of epithelial cells cortex contained atrophied ovarian follicles with degenerated Oocytes, the medulla of the ovary contained congested blood vessels hemorrhage in the interstitial connective tissue of the medulla also hemolysis blood of blood capillaries While the second part, the second part was to evaluate the effect of the drug on reproductive efficiency. Four groups were divided, each group containing five rats, and were given the same dose for a month. After treatment, a male was introduced to each group and left to mate with the females. The result was pregnancy and births only in the control group, while no pregnancy occurred in the other group, The administration of isotretinoin, particularly in elevated doses, poses substantial risks to female reproductive efficacy, notably affecting ovarian reserve, a key fertility determinant.
Downloads
Metrics
References
Abadie, R. B., Keller, C. L., Jones, N. T., Mayeux, E. L., Klapper, R. J., Anderson, L., Kaye, A. M., Ahmadzadeh, S., Varrassi, G., & Shekoohi, S. (2023). Review of Teratogenic Effects of Leflunomide, Accutane, Thalidomide, Warfarin, Tetracycline, and Angiotensin-Converting Enzyme Inhibitors. Cureus, 15(12).
Abali, R., Yuksel, M. A., Aktas, C., Celik, C., Guzel, S., Erfan, G., & Sahin, O. (2013). Decreased ovarian reserve in female Sprague–Dawley rats induced by isotretinoin (retinoic acid) exposure. Reproductive Biomedicine Online, 27(2), 184–191.
Abdelhamed, A., El-Dawla, R. E., Karadag, A. S., Agamia, N. F., & Melnik, B. C. (2021). The impact of isotretinoin on the pituitary-ovarian axis: An interpretative review of the literature. Reproductive Toxicology, 104, 85–95.
Abdelmaksoud, A., Lotti, T., Anadolu, R., Goldust, M., Ayhan, E., Dave, D. D., Vestita, M., Ebik, B., & Gupta, M. (2020). Low dose of isotretinoin: a comprehensive review. Dermatologic Therapy, 33(2), e13251.
Abou Zommar, G. O. H., Nofal, A., & Ibrahim, A. S. M. (2022). Possible Side Effects of Isotretinoin Use in Dermatology. The Egyptian Journal of Hospital Medicine, 89(1), 4562–4565.
Acmaz, G., Cınar, L., Acmaz, B., Aksoy, H., Kafadar, Y. T., Madendag, Y., Ozdemir, F., Sahin, E., & Muderris, I. (2019). The effects of oral isotretinoin in women with acne and polycystic ovary syndrome. BioMed Research International, 2019(1), 2513067.
Agamia, N. F., El Mulla, K. F., Alsayed, N. M., Ghazala, R. M., El Maksoud, R. E. A., Abdelmeniem, I. M., Talaat, I. M., Zaki, I. I., Sabah, R. M., & Melnik, B. C. (2023). Isotretinoin treatment upregulates the expression of p53 in the skin and sebaceous glands of patients with acne vulgaris. Archives of Dermatological Research, 315(5), 1355–1365.
Ahmetašević-Demirović, A., Lagumdžija, D., & Pehlivanović Kelle, B. (2023). Application of Isotretinoin in the Treatment of Acne Vulgaris: A Questionnaire-Based Survey. Mediterranean Conference on Medical and Biological Engineering and Computing, 368–376.
Akpolat, D. (2021). Unexpected effects of oral isotretinoin in adolescents with acne vulgaris. Cureus, 13(8).
Aksoy, H., Cinar, L., Acmaz, G., Aksoy, U., Aydin, T., Vurdem, U. E., Oz, L., Idem Karadag, O., & Kartal, D. (2015). The effect of isotretinoin on ovarian reserve based on hormonal parameters, ovarian volume, and antral follicle count in women with acne. Gynecologic and Obstetric Investigation, 79(2), 78–82.
Aktar, R., Gunes Bilgili, S., Yavuz, I. H., Ozaydin Yavuz, G., Aktar, S., Ozturk, M., & Karadağ, A. S. (2021). Evaluation of hirsutism and hormonal parameters in acne vulgaris patients treated with isotretinoin. International Journal of Clinical Practice, 75(3), e13791.
Al Muqarrab, F., & Almohssen, A. (2022). Low‐dose oral isotretinoin for the treatment of adult patients with mild‐to‐moderate acne vulgaris: Systematic review and meta‐analysis. Dermatologic Therapy, 35(4), e15311.
Alajaji, A., Alrawaf, F. A., Alosayli, S. I., Alqifari, H. N., Alhabdan, B. M., & Alnasser, M. A. (2021). Laboratory abnormalities in acne patients treated with oral isotretinoin: a retrospective epidemiological study. Cureus, 13(10).
Tawfiq, P., Sharef, T. Y., Ali, K. A., and Salih, L. S. (2020). Effect of Isotretinion on Rat’s Liver and Aptness of Cumin Oil in Protection. Diyala Journal of Medicine, 18(2), 32–43.
Bas, S., Cetinkaya, N., Ozgu, E., Korkmaz, E., Oz, M., Isikalan, M., Caydere, M., Hucumenoglu, S., Gungor, T., and Buyukkagnici, U. (2023). The protective effects of hormonal suppression by a gonadotropin-releasing hormone agonist or an oral contraceptive on the decreased ovarian reserve in female rats exposed to isotretinoin. European Review for Medical and Pharmacological Sciences, 27(18).
Kacamak, P., Ozogul, C., Saribas, G. S., Akarca Dizakar, S. O., and Emniyet Sert, A. A. (2020). The Effect of Isotretinoin on Oocyte Maturation in Adolescent Female Rats. Gynecologic and Obstetric Investigation, 85(4), 327–335.
Vickery BH, Bennett JP (1970) Rats and mice. In: Hafez ESE (ed). Repro duction and beeding techniques for laboratory animals. Philadelphia:Lea and Febiger, p. 299–315.
Downloads
Published
How to Cite
Issue
Section
License

This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material for any purpose, even commercially.
Terms:
- Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.