title: Sodium fluoride activates ERK and JNK via induction of oxidative stress to promote apoptosis and impairs ovarian function in rats.
abstract: The toxicity of sodium fluoride (NaF) to female fertility is currently recognized; however, the mechanisms are unclear. Previously, we reported a reduction in successful pregnancy rates, ovarian atrophy and dysfunction following exposure to NaF. The purpose of this study was to elucidate the underlying molecular mechanisms. Female Sprague-Dawley rats (10 rats/group) received 100 or 200mg/L NaF in their drinking water for 6 months or were assigned to an untreated control group. Apoptotic indices and oxidative stress indicators in blood and ovarian tissue were analyzed following sacrifice. The results confirmed the NaF-induced ovarian apoptosis, with concomitant activation of oxidative stress. Further investigations in ovarian granular cells showed that exposure to NaF activated extracellular regulated protein kinase (ERK) and c-Jun NH2 kinase (JNK), disrupting the ERK and JNK signaling pathways, while p38 and PI3K remained unchanged. These data demonstrated that oxidative stress may play a key role in NaF-induced ovarian dysfunction by activating the apoptotic ERK and JNK signaling pathways.
authors.affiliation: Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No. 1 Yixueyuan Road, Yuzhong District, 400016 Chongqing, PR China. Electronic address: aqing000@163.com.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Geng
authors.affiliation: Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No. 1 Yixueyuan Road, Yuzhong District, 400016 Chongqing, PR China. Electronic address: 496597283@qq.com.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No. 1 Yixueyuan Road, Yuzhong District, 400016 Chongqing, PR China. Electronic address: a68733172@online.cq.cn.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No. 1 Yixueyuan Road, Yuzhong District, 400016 Chongqing, PR China. Electronic address: shirly-cxm@163.com.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No. 1 Yixueyuan Road, Yuzhong District, 400016 Chongqing, PR China. Electronic address: dingyb@gmail.com.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No. 1 Yixueyuan Road, Yuzhong District, 400016 Chongqing, PR China. Electronic address: Liushangjing123@126.com.
authors.forename: Shangjing
authors.initials: S
authors.lastname: Liu
authors.affiliation: Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No. 1 Yixueyuan Road, Yuzhong District, 400016 Chongqing, PR China. Electronic address: xiaobaozi1225@gmail.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No. 1 Yixueyuan Road, Yuzhong District, 400016 Chongqing, PR China. Electronic address: gao_ru_fei@163.com.
authors.forename: Rufei
authors.initials: R
authors.lastname: Gao
authors.affiliation: Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No. 1 Yixueyuan Road, Yuzhong District, 400016 Chongqing, PR China. Electronic address: wyx61221@aliyun.com.
authors.forename: Yingxiong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No. 1 Yixueyuan Road, Yuzhong District, 400016 Chongqing, PR China. Electronic address: hejunlin_11@aliyun.com.
authors.forename: Junlin
authors.initials: J
authors.lastname: He
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D005298:Fertility / Q000187:drug effects; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D010053:Ovary / Q000187:drug effects* / Q000503:physiopathology; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D012969:Sodium Fluoride / Q000737:chemistry*
chemical_list: D017382:Reactive Oxygen Species; D012969:Sodium Fluoride; D048049:Extracellular Signal-Regulated MAP Kinases; D048670:MAP Kinase Kinase 4
keywords: Female reproduction; Ovarian apoptosis; Oxidative stress; Sodium fluoride