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Exosomal miR-27 negatively regulates ROS production and promotes granulosa cells apoptosis by targeting SPRY2 in OHSS
Authors:Kailu Liu  Weijie Yang  Mengting Hu  WenXiu Xie  Jingyu Huang  Meiting Cui  Xi He  Xiaowei Nie
Institution:1. Department of Reproductive Medicine, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China

Contribution: Data curation (lead), Formal analysis (lead), ?Investigation (lead), Project administration (lead), Writing - original draft (lead);2. Assisted Reproduction Unit, Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China

Contribution: Data curation (equal), Project administration (lead);3. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China

State Key Laboratory of Reproductive Medicine, Clinical Center for Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

Contribution: Data curation (supporting), Formal analysis (supporting);4. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China

Contribution: Formal analysis (equal), Resources (equal);5. Department of Reproductive Medicine, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China

Contribution: Data curation (lead), Methodology (equal), Project administration (equal);6. Department of Reproductive Medicine, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China

Contribution: Formal analysis (equal), Methodology (equal);7. Department of Human Anatomy and Histoembryology, Nanjing University of Chinese Medicine, Nanjing, China;8. Department of Reproductive Medicine, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China

Abstract:Ovarian hyperstimulation syndrome (OHSS) is one of the most dangerous iatrogenic complications in controlled ovarian hyperstimulation (COH). The exact molecular mechanism that induces OHSS remains unclear. In recent years, accumulating evidence found that exosomal miRNAs participate in many diseases of reproductive system. However, the specific role of miRNAs, particularly the follicular fluid-derived exosomal miRNAs in OHSS remains controversial. To identify differentially expressed follicular fluid exosomal miRNAs from OHSS and non-OHSS patients, the analysis based on miRNA-sequence was conducted. The levels of 291 miRNAs were significantly differed in exosomes from OHSS patients compared with normal control, and exosomal miR-27 was one of the most significantly down-regulated miRNAs in the OHSS group. By using MiR-27 mimic, we found it could increase ROS stress and apoptosis by down-regulating the expression of p-ERK/Nrf2 pathway by negatively regulating SPRY2. These data demonstrate that exosomal miRNAs are differentially expressed in follicular fluid between patients with and without OHSS, and follicular fluid exosomal miR-27 may involve in the pathological process of OHSS development.
Keywords:exosome  follicular fluid  miRNAs  OHSS
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