Gökçe Ceren Kuşçu1, Çevik Gürel1,2, Aylin Buhur1, Fatih Oltulu1, Levent Akman3, Timur Köse4, Nefise Ülkü Karabay Yavaşoğlu5, Altuğ Yavaşoğlu1. 1. Department of Histology and Embryology, Faculty of Medicine, Ege University, Izmir, Turkey. 2. Department of Histology and Embryology, Faculty of Medicine, Harran University, Sanliurfa, Turkey. 3. Department of Obstetrics and Gynecology, Faculty of Medicine, Ege University, Izmir, Turkey. 4. Department of Biostatistics and Medical Informatics, Faculty of Medicine, Ege University, Izmir, Turkey. 5. Department of Biology, Faculty of Science, Ege University, Bornova, 35100, Izmir, Turkey. ulku.karabay@ege.edu.tr.
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.
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.
Authors: M F Costello; M L Misso; A Balen; J Boyle; L Devoto; R M Garad; R Hart; L Johnson; C Jordan; R S Legro; R J Norman; E Mocanu; J Qiao; R J Rodgers; L Rombauts; E C Tassone; S Thangaratinam; E Vanky; H J Teede Journal: Hum Reprod Open Date: 2019-01-04