title: Mitochondrial Uncoupling Protein 2 in human cumulus cells is associated with regulating autophagy and apoptosis, maintaining gap junction integrity and progesterone synthesis.
abstract: To explore the roles of mitochondrial Uncoupling Protein 2 (UCP2) in cumulus cells (CCs), human CCs were cultured in vitro, and the UCP2 was inhibited by treatment with Genipin, a special UCP inhibitor, or by RNA interference targeting UCP2. No significant differences in adenosine triphosphate levels and the ratio of ADP/ATP were observed after UCP2 inhibition. UCP2 inhibition caused a significant increase in cellular oxidative damage, which was reflected in alterations to several key parameters, including reactive oxygen species (ROS) and lipid peroxidation levels and the ratio of reduced GSH to GSSG. UCP2 blocking resulted in an obvious increase in active Caspase-3, accompanied by the decline of proactive Caspase-3 and a significant increase in the LC3-II/LC3-I ratio, suggesting that UCP2 inhibition triggered cellular apoptosis and autophagy. The mRNA and protein expression of connexin 43 (Cx43), a gap junction channel protein, were significantly reduced after treatment with Genipin or siRNA. The progesterone level in the culture medium was also significantly decreased after UCP2 inhibition. Our data indicated that UCP2 plays highly important roles in mediating ROS production and regulating apoptosis and autophagy, as well as maintaining gap junction integrity and progesterone synthesis, which suggests that UCP2 is involved in the regulation of follicle development and early embryo implantation and implies that it might serve as a potential biomarker for oocyte quality and competency.
authors.affiliation: Center for Reproductive Medicine, Department of Obstetrics and Gynaecology, Taizhou People's Hospital, The Fifth Hospital Affiliated Nantong University, Taizhou, Jiangsu Province, 225300, People's Republic of China; The Second Affiliated Hospital and YuYing Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, People's Republic of China. Electronic address: dafeng76@126.com.
authors.forename: Hongshan
authors.initials: H
authors.lastname: Ge
authors.affiliation: The Second Affiliated Hospital and YuYing Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, People's Republic of China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: The Second Affiliated Hospital and YuYing Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Duan
authors.affiliation: The Second Affiliated Hospital and YuYing Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhu
authors.affiliation: The Second Affiliated Hospital and YuYing Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, People's Republic of China.
authors.forename: Jiayan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Maternal and Child Health Hospital, Zhoushan Hospital Affiliated Wenzhou Medical University, Zhejiang Province, 316100, People's Republic of China.
authors.forename: Feijun
authors.initials: F
authors.lastname: Ye
authors.affiliation: The Second Affiliated Hospital and YuYing Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Shan
authors.affiliation: The Second Affiliated Hospital and YuYing Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.affiliation: The Second Affiliated Hospital and YuYing Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, People's Republic of China.
authors.forename: XiaoSheng
authors.initials: X
authors.lastname: Lu
authors.affiliation: The Second Affiliated Hospital and YuYing Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, People's Republic of China.
authors.forename: ChunFang
authors.initials: C
authors.lastname: Zhu
authors.affiliation: The Second Affiliated Hospital and YuYing Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, People's Republic of China.
authors.forename: Renshan
authors.initials: R
authors.lastname: Ge
authors.affiliation: The Second Affiliated Hospital and YuYing Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, People's Republic of China. Electronic address: zklin@wmu.edu.cn.
authors.forename: Zhenkun
authors.initials: Z
authors.lastname: Lin
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D054885:Cumulus Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D039823:Iridoids / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011374:Progesterone / Q000096:biosynthesis*; D034741:RNA, Small Interfering / Q000378:metabolism; D000071246:Uncoupling Protein 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D039823:Iridoids; D034741:RNA, Small Interfering; D000071246:Uncoupling Protein 2; D011374:Progesterone; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C007834:genipin
keywords: Apoptosis; Autophagy; Cumulus cells; Gap junction; Progesterone synthesis; Uncoupling Protein 2