Melatonin Inhibits Oxidative Stress and Apoptosis in Cryopreserved Ovarian Tissues via Nrf2/HO-1 Signaling Pathway

Tie Cheng Sun; Xiao Chao Liu; Song He Yang; Ling Li Song; Shan Jie Zhou; Shou Long Deng; Li Tian; Lu Yang Cheng

doi:10.3389/fmolb.2020.00163

Melatonin Inhibits Oxidative Stress and Apoptosis in Cryopreserved Ovarian Tissues via Nrf2/HO-1 Signaling Pathway

Front Mol Biosci. 2020 Jul 29:7:163. doi: 10.3389/fmolb.2020.00163. eCollection 2020.

Authors

Tie Cheng Sun^{1

2

3}, Xiao Chao Liu^{1

2}, Song He Yang^{1

2}, Ling Li Song², Shan Jie Zhou², Shou Long Deng⁴, Li Tian³, Lu Yang Cheng^{1

2}

Affiliations

¹ Faculty of Graduate Studies, Chengde Medical University, Chengde, China.
² Department of Immunology, Basic Medical Institute, Chengde Medical University, Chengde, China.
³ Reproductive Medicine Center, Department of Obstetrics and Gynecology, Peking University International Hospital, Beijing, China.
⁴ CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.

Abstract

In the field of assisted reproductive technology, female fertility preservation, particularly ovarian tissue cryopreservation in adolescent cancer patients, has attracted much attention. Melatonin (MLT) is well known for its antioxidative and anti-apoptotic properties; however, whether it can ameliorate the cryoinjury and inhibit the generation of reactive oxygen species (ROS) in cryopreserved ovarian tissues (OTs) has not yet been reported. Here, we demonstrated that MLT could protect follicular integrity; prevent cell apoptosis; decrease ROS, malondialdehyde (MDA), and nitric oxide (NO) levels; and increase activities of glutathione peroxidases (GSH-Px), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) in cryopreserved OTs. Furthermore, these effects may be related with the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, as evidenced by increased mRNA levels of Nrf2 downstream genes, including heme oxygenase-1 (HO-1), glutathione S-transferase M1 (GSTM1), SOD, and CAT. In summary, MLT can not only directly scavenge ROS but also significantly induce the activation of antioxidative enzymes via the Nrf2 signaling pathway, which is a new mechanism underlying the protection effects of MLT on cryopreserved OTs.

Keywords: Nrf2 signaling pathway; ROS; cryopreserved ovarian tissue; melatonin; oxidative stress.