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The regulatory effects of clomiphene and tamoxifen on mTOR and LC3-II expressions in relation to autophagy in experimental polycystic ovary syndrome (PCOS)

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Abstract

Background

Polycystic ovary syndrome (PCOS) is a metabolic disease that causes infertility due to anovulation in women in reproductive age. It is known that clomiphene citrate (CC) and tamoxifen citrate (TMX) induce ovulation in women with PCOS. In this study, we aimed to investigate the effects of CC and TMX on the autophagy pathway in PCOS.

Methods and results

Experimental PCOS model was induced by letrozole (1 mg/kg) in rats by gavage for 21 days. After the last letrozole administration, rats were treated TMX (1 mg/kg) or CC (1 mg/kg) for 5 days. At the end of the experimental procedures, rats in all groups were sacrificed and ovarian tissues were removed. It was observed that mRNA and protein expressions of LC3-II were significantly higher in TMX and CC groups than control and PCOS groups (p < 0.05), while mRNA and protein expressions of mTOR in TMX and CC groups were found significantly lower than control and PCOS groups (p < 0.05).

Conclusions

In conclusion, present study suggests that TMX and CC induce autophagy in ovaries with PCOS. Autophagy is a promising target for understanding pathophysiology of this disease and for developing more effective and safe new protocols for the treatment of PCOS-related anovulation.

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Data availability

Data available on request from the authors.

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Acknowledgements

The authors wish to thank Dr. Gürkan Yiğittürk and Ege University, Drug Research and Development and Pharmacokinetic Applications (ARGEFAR).

Funding

This study was supported by the Ege University Research Fund [Grant number BAP-17-TIP-029 (to Altuğ Yavaşoğlu)].

Author information

Authors and Affiliations

  1. Department of Histology and Embryology, Faculty of Medicine, Ege University, Izmir, Turkey

    Gökçe Ceren Kuşçu, Çevik Gürel, Aylin Buhur, Fatih Oltulu & Altuğ Yavaşoğlu

  2. Department of Histology and Embryology, Faculty of Medicine, Harran University, Sanliurfa, Turkey

    Çevik Gürel

  3. Department of Obstetrics and Gynecology, Faculty of Medicine, Ege University, Izmir, Turkey

    Levent Akman

  4. Department of Biostatistics and Medical Informatics, Faculty of Medicine, Ege University, Izmir, Turkey

    Timur Köse

  5. Department of Biology, Faculty of Science, Ege University, Bornova, 35100, Izmir, Turkey

    Nefise Ülkü Karabay Yavaşoğlu

Authors
  1. Gökçe Ceren Kuşçu
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  2. Çevik Gürel
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  3. Aylin Buhur
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  4. Fatih Oltulu
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  5. Levent Akman
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  7. Nefise Ülkü Karabay Yavaşoğlu
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  8. Altuğ Yavaşoğlu
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Contributions

The study was designed by AY and GCK. Histochemical and immunohistochemical staining were performed by FO, GCK and AB. Real-Time PCR was performed by ÇG and NUKY. LA, ÇG, and GCK contributed to the data collection. Statistical analysis was performed by TK. All authors contributed to the writing of the manuscript. AY are responsible for supervising of the manuscript.

Corresponding author

Correspondence to Nefise Ülkü Karabay Yavaşoğlu.

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Ethical approval

The protocol was approved by Ege University, Local Ethics Committee for Animal Experiments (Approval no: 2017-006).

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Kuşçu, G.C., Gürel, Ç., Buhur, A. et al. The regulatory effects of clomiphene and tamoxifen on mTOR and LC3-II expressions in relation to autophagy in experimental polycystic ovary syndrome (PCOS). Mol Biol Rep 49, 1721–1729 (2022). https://doi.org/10.1007/s11033-021-06981-y

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