Evaluation of the effects of tamoxifen and clomiphene on ovarian tissue in experimental polycystic ovary syndrome (pcos) model in the terms of autophagy

Polycystic ovary syndrome (PCOS), is a endocrine disorder characterized with menstrual dysfunction, hyperandrogenism, hirsutism, infertility and polycystic ovary. This disease affects 5% to 10% of women in reproductive age and is one of the most important causes of infertility caused by anovulation. Clomiphene, the most commonly used drug in the treatment of infertility caused by PCOS, binds to the estrogen receptors found in the hypothalamus, preventing the negative feed-back mechanism of estrogen. This leads to an increase in the FSH and stimulate the ovulation. Tamoxifen is a nonsteroidal selective estrogen modulator such as clomiphene and is structurally similar with clomiphene. Even though tamoxifen is mainly used in the treatment of breast cancer, studies on ovulation induction have shown that tamoxifen reaches ovulation and pregnancy rates similar to clomiphene. In our study, the PCOS model was generated by administering 1 mg / kg Letrozol to female rats for 21 days by gavage method. Then, tamoxifen and clomiphene were applied to female rats for 5 days based on the group name. At the end of the application period, ovarian tissues from the sacrificed animals were analyzed by histochemical, immunohistochemical staining and Real time-PCR (RT-PCR) technique and the efficacy of these drugs on ovarian tissue was investigated in relation to the autophagic pathway. In our study, immunohistochemical stainings and RT-PCR analyzes showed that the expression of LC3 in the tamoxifen and clomiphene groups increased and the expression of mTOR decreased. Based on these findings, we have found that tamoxifen and clomiphene can induce autophagy in ovaries with PCOS.