The Protective Effect of Coenzyme Q10 on Serum Anti-Müllerian Hormone Levels in Rats Treated with Cyclophosphamide

Abstract

Anti-Müllerian hormone (AMH) is widely used in veterinary medicine to assess reproductive health. Cyclophosphamide (CP) is a chemotherapeutic and immunosuppressive drug that has been reported to reduce AMH levels and cause damage to ovarian reserves, although findings vary depending on study design. Coenzyme Q10 (CoQ10), known for its antioxidant properties, has been suggested to have a protective role against oxidative stress-related ovarian damage. This study was conducted to examine how CP affects serum AMH levels in rats and whether CoQ10 supplementation could help reduce any negative impact. A total of 35 Wistar Albino rats were used in the study. They were divided into five groups: control, sham, CP, CoQ10, and CP+CoQ10. All substances were administered by oral gavage. CP was dissolved in distilled water and administered at a dose of 6 mg/kg/day, while CoQ10 was dissolved in olive oil and given at a dose of 2.8 mg/kg/day. The treatments lasted for four weeks. Results showed that CP alone did not significantly change AMH levels (p>0.05). In contrast, CoQ10 alone led to a significant increase in serum AMH levels (p<0.05). However, when CP and CoQ10 were given together, no significant difference in AMH levels was observed. This may suggest that CP interferes with or masks the effect of CoQ10 on the ovaries. These findings may contribute to a better understanding of the interaction between CP and CoQ10, especially in terms of dosage, duration and timing of treatment, in future studies.

Keywords

• AMH
• Cyclophosphamide
• Coenzyme Q10
• Rat

Siklofosfamid ile Tedavi Edilen Ratlarda Serum Anti-Müllerian Hormon Düzeyleri Üzerinde Koenzim Q10'un Koruyucu Etkisi

Abstract

Anti-Müllerian hormon (AMH), veteriner hekimlikte reprodüktif sağlığını değerlendirmek için yaygın olarak kullanılmaktadır. Siklofosfamid (CP), AMH düzeylerini düşürdüğü ve ovaryum rezervlerine zarar verdiği bildirilen kemoterapötik ve immünosüpresif bir ilaçtır. Ancak bulgular çalışma tasarımına bağlı olarak değişiklik göstermektedir. Antioksidan özelliğiyle bilinen Koenzim Q10'un (CoQ10), oksidatif strese bağlı ovaryum hasarına karşı koruyucu bir rolü olduğu öne sürülmektedir. Bu çalışma, CP'nin sıçanlarda serum AMH düzeylerini nasıl etkilediğini ve CoQ10 takviyesinin herhangi bir olumsuz etkiyi azaltmaya yardımcı olup olamayacağını incelemek amacıyla yürütülmüştür. Çalışmada toplam 35 Wistar Albino sıçanı kullanılmıştır. Sıçanlar beş gruba ayrılmıştır: kontrol, sham, CP, CoQ10 ve CP+CoQ10. Tüm maddeler oral gavaj yoluyla uygulanmıştır. CP, distile suda çözülerek 6 mg/kg/gün dozunda uygulanırken, CoQ10 zeytinyağında çözülerek 2,8 mg/kg/gün dozunda uygulandı. Tedaviler dört hafta sürdü. Sonuçlar, CP'nin tek başına AMH seviyelerinde anlamlı bir değişiklik oluşturmadığı görüldü (p > 0,05). Buna karşılık, CoQ10 tek başına serum AMH seviyelerinde anlamlı bir artışa yol açtı (p<0,05). Ancak CP ve CoQ10 birlikte uygulandığında, AMH seviyelerinde anlamlı bir fark gözlenmedi. Bu durum, CP'nin CoQ10'un ovaryum üzerindeki etkisini engellediğini veya maskelediğini düşündürdü. Bu bulgular, özellikle dozaj, tedavi süresi ve zamanlaması açısından, CP ve CoQ10 arasındaki etkileşimin gelecekteki çalışmalarda daha iyi anlaşılmasına katkıda bulunabilir.

Keywords

• AMH
• Koenzim Q10
• Sıçan
• Siklofosfamid

References

1. Ahlmann, M., & Hempel, G. (2016). The effect of cyclophosphamide on the immune system: implications for clinical cancer therapy. *Cancer Chemotherapy and Pharmacology*, 78(4), 661–671. [https://doi.org/10.1007/s00280-016-3152-1](https://doi.org/10.1007/s00280-016-3152-1)
2. Barton, T. S., Wyrobek, A. J., Hill, F. S., Robaire, B., & Hales, B. F. (2003). Numerical chromosomal abnormalities in rat epididymal spermatozoa following chronic cyclophosphamide exposure. *Biology of Reproduction*, 69(4), 1150–1157. [https://doi.org/10.1095/biolreprod.103.016261](https://doi.org/10.1095/biolreprod.103.016261)
3. Ben Meir, A., Burstein, E., Borrego Álvarez, A., et al. (2015). Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging. *Aging Cell*, 14(5), 887–895. [https://doi.org/10.1111/acel.12368](https://doi.org/10.1111/acel.12368)
4. Bentov, Y., Hannam, T., Jurisicova, A., Esfandiari, N., & Casper, R. F. (2014). Coenzyme Q10 supplementation and oocyte aneuploidy in women undergoing IVF-ICSI treatment. *Clinical Medicine Insights: Reproductive Health*, 8, CMRH-S14681. [https://doi.org/10.4137/CMRH.S14681](https://doi.org/10.4137/CMRH.S14681)
5. Emadi, A., Jones, R. J., & Brodsky, R. A. (2009). Cyclophosphamide and cancer: golden anniversary. *Nature Reviews Clinical Oncology*, 6(11), 638–647. [https://doi.org/10.1038/nrclinonc.2009.146](https://doi.org/10.1038/nrclinonc.2009.146)
6. Gephart, B. D., Coulter, D. W., & Solheim, J. C. (2025). Effects of the alkylating agent cyclophosphamide in potentiating anti-tumor immunity. *International Journal of Molecular Sciences*, 26(13), 6440. [https://doi.org/10.3390/ijms26136440](https://doi.org/10.3390/ijms26136440)
7. Ghosh, D., Das, U. B., Ghosh, S., Mallick, M., & Debnath, J. (2002). Testicular gametogenic and steroidogenic activities in cyclophosphamide treated rat: a correlative study with testicular oxidative stress. *Drug and Chemical Toxicology*, 25(3), 281–292. [https://doi.org/10.1081/DCT-120005891](https://doi.org/10.1081/DCT-120005891)
8. Hao, X., Reyes Palomares, A., Anastácio, A., Liu, K., & Rodriguez-Wallberg, K. A. (2024). Evidence of apoptosis as an early event leading to cyclophosphamide-induced primordial follicle depletion in a prepubertal mouse model. *Frontiers in Endocrinology*, 15, 1322592. [https://doi.org/10.3389/fendo.2024.1322592](https://doi.org/10.3389/fendo.2024.1322592)

9. Hassanzadeh-Taheri, M., Hosseini, M., Hassanpour-Fard, M., Ghiravani, Z., Vazifeshenas-Darmiyan, K., Yousefi, S., & Ezi, S. (2016). Effect of turnip leaf and root extracts on renal function in diabetic rats. *Oriental Pharmacy and Experimental Medicine*, 16(4), 279–286. [https://doi.org/10.1007/s13596-016-0249-3](https://doi.org/10.1007/s13596-016-0249-3)
10. Hidalgo-Gutiérrez, A., González-García, P., Díaz-Casado, M. E., Barriocanal-Casado, E., López-Herrador, S., Quinzii, C. M., & López, L. C. (2021). Metabolic targets of coenzyme Q10 in mitochondria. *Antioxidants*, 10(4), 520. [https://doi.org/10.3390/antiox10040520](https://doi.org/10.3390/antiox10040520)
11. Hou, S., Tian, Z., Zhao, D., Liang, Y., Dai, S., Ji, Q., ... & Yang, Y. (2023). Efficacy and optimal dose of coenzyme Q10 supplementation on inflammation-related biomarkers: a GRADE-assessed systematic review and updated meta-analysis of randomized controlled trials. *Molecular Nutrition & Food Research*, 67(13), 2200800. [https://doi.org/10.1002/mnfr.202200800](https://doi.org/10.1002/mnfr.202200800)
12. Jeelani, R., Khan, S. N., Shaeib, F., Kohan-Ghadr, H. R., Aldhaheri, S. R., Najafi, T., ... & Abu-Soud, H. M. (2017). Cyclophosphamide and acrolein induced oxidative stress leading to deterioration of metaphase II mouse oocyte quality. *Free Radical Biology and Medicine*, 110, 11–18. [https://doi.org/10.1016/j.freeradbiomed.2017.05.006](https://doi.org/10.1016/j.freeradbiomed.2017.05.006)
13. Koşal, V., Rua, İ., Yüksek, V., & Keleş, Ö. (2023). Investigation of the effect of coenzyme Q10 on cyclophosphamide-induced testicular damage in male rats. *Revista Científica de la Facultad de Veterinaria*, 33(2). [http://doi.org/10.52973/rcfcv-e33278](http://doi.org/10.52973/rcfcv-e33278)
14. La Marca, A., & Volpe, A. (2006). Anti-Müllerian hormone (AMH) in female reproduction: is measurement of circulating AMH a useful tool? *Clinical Endocrinology*, 64(6), 603–610. [https://doi.org/10.1111/j.1365-2265.2006.02533.x](https://doi.org/10.1111/j.1365-2265.2006.02533.x)
15. Özcan, P., Fıçıcıoğlu, C., Kizilkale, O., Yesiladali, M., Tok, O. E., Ozkan, F., & Esrefoglu, M. (2016). Can coenzyme Q10 supplementation protect the ovarian reserve against oxidative damage? *Journal of Assisted Reproduction and Genetics*, 33(9), 1223–1230. [https://doi.org/10.1007/s10815-016-0751-z](https://doi.org/10.1007/s10815-016-0751-z)
16. Rodríguez-Varela, C., & Labarta, E. (2021). Does coenzyme Q10 supplementation improve human oocyte quality? *International Journal of Molecular Sciences*, 22(17), 9541. [https://doi.org/10.3390/ijms22179541](https://doi.org/10.3390/ijms22179541)
17. Rose, D. P., & Davis, T. E. (1977). Ovarian function in patients receiving adjuvant chemotherapy for breast cancer. *The Lancet*, 309(8023), 1174–1176. [https://doi.org/10.1016/S0140-6736(77)92716-7](https://doi.org/10.1016/S0140-6736%2877%2992716-7)
18. Türk, P. (2016). *Siklofosfamide Bağlı Ovaryan Toksisiteyi Azaltmada Silymarinin Rolü*. Specialization Thesis, Faculty of Medicine, Uludağ University, Bursa, Türkiye.
19. Villalba, J. M., & Navas, P. (2000). Plasma membrane redox system in the control of stress-induced apoptosis. *Antioxidants & Redox Signaling*, 2(2), 213–230. [https://doi.org/10.1089/ars.2000.2.2-213](https://doi.org/10.1089/ars.2000.2.2-213)
20. Weenen, C., Laven, J. S., Von Bergh, A. R., Cranfield, M., Groome, N. P., Visser, J. A., ... & Themmen, A. P. (2004). Anti-Müllerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. *Molecular Human Reproduction*, 10(2), 77–83. [https://doi.org/10.1093/molehr/gah015](https://doi.org/10.1093/molehr/gah015)
21. Xu, Y., Nisenblat, V., Lu, C., Li, R., Qiao, J., Zhen, X., & Wang, S. (2018). Pretreatment with coenzyme Q10 improves ovarian response and embryo quality in low-prognosis young women with decreased ovarian reserve: a randomized controlled trial. *Reproductive Biology and Endocrinology*, 16(1), 29. [https://doi.org/10.1186/s12958-018-0343-0](https://doi.org/10.1186/s12958-018-0343-0)
22. Yildiz, M., Koca, D., Kilic Yildiz, B. N., Isik, M. Z., Turgut, A. O., & Çetin, Y. (2025). The role of anti-Müllerian hormone in Van cats in relation to sex and reproductive status. *Veterinary Medicine and Science*, 11(4), e70502. [https://doi.org/10.1002/vms3.70502](https://doi.org/10.1002/vms3.70502)
23. Zan, E., & Duran, B. (2020). DHEA supplementation prevents follicle depletion due to chemotherapy-induced ovarian damage. *EC Endocrinology and Metabolic Research*, 5, 01–04.