miR-484 mediates oxidative stress-induced ovarian dysfunction and promotes granulosa cell apoptosis via SESN2 downregulation
Xiaofei Wang,
Jiahao Yang,
Huiying Li,
Hongbei Mu,
Ling Zeng,
Siying Cai,
Ping Su,
Huaibiao Li,
Ling Zhang,
Wenpei Xiang
Affiliations
Xiaofei Wang
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China
Jiahao Yang
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China
Huiying Li
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China
Hongbei Mu
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China
Ling Zeng
Medical Genetics Center, Maternal and Child Health Hospital of Hubei Province, Wuhan, 430070, China
Siying Cai
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China
Ping Su
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China; Wuhan Huake Reproductive Hospital, 128 Sanyang Road, Wuhan, 430013, China
Huaibiao Li
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China; Corresponding author.
Ling Zhang
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China; Wuhan Huake Reproductive Hospital, 128 Sanyang Road, Wuhan, 430013, China; Corresponding author. Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China.
Wenpei Xiang
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China; Wuhan Huake Reproductive Hospital, 128 Sanyang Road, Wuhan, 430013, China; Corresponding author. Wuhan Huake Reproductive Hospital, 128 Sanyang Road, Wuhan, 430013, China.
Ovarian dysfunction is a common cause of female infertility, which is associated with genetic, autoimmune and environmental factors. Granulosa cells (GCs) constitute the largest cell population of ovarian follicles. Changes in GCs, including oxidative stress (OS) and excessive reactive oxygen species (ROS), are involved in regulating ovary function. miR-484 is highly expressed in 3-NP-induced oxidative stress models of ovaries and GCs. miR-484 overexpression aggravated GCs dysfunction and thereby intensified ovarian oxidative stress injury in mice. Moreover, bioinformatic analyses, luciferase assays and pull-down assays indicated that LINC00958 acted as a competing endogenous RNA (ceRNA) for miR-484 and formed a signaling axis with Sestrin2(SESN2) under oxidative stress conditions, which in turn regulated mitochondrial functions and mitochondrial-related apoptosis in GCs. Additionally, the inhibition of miR-484 alleviated GCs dysfunction under ovarian oxidative stress condition. Our present study revealed the role of miR-484 in oxidative stress of ovaries and GCs and the function of LINC00958/miR-484/SESN2 axis in mitochondrial function and mitochondria-related apoptosis.
