title: The regulation of cellular apoptosis by the ROS-triggered PERK/EIF2α/chop pathway plays a vital role in bisphenol A-induced male reproductive toxicity.
abstract: Bisphenol A (2,2-bis(4-hydroxyphenyl)propane, BPA) is ubiquitous in the environment, wildlife, and humans. Evidence from past studies suggests that BPA is associated with decreased semen quality. However, the molecular basis for the adverse effect of BPA on male reproductive toxicity remains unclear. We evaluated the effect of BPA on mouse spermatocytes GC-2 cells and adult mice, and we explored the potential mechanism of its action. The results showed that BPA inhibited cell proliferation and increased the apoptosis rate. The testes from BPA-treated mice showed fewer spermatogenic cells and sperm in the seminiferous tubules. In addition, BPA caused reactive oxygen species (ROS) accumulation. Previous study has verified that mitochondrion was the organelle affected by the BPA-triggered ROS accumulation. We found that BPA induced damage to the endoplasmic reticulum (ER) in addition to mitochondria, and most ER stress-related proteins were activated in cellular and animal models. Knocking down of the PERK/EIF2α/chop pathway, one of the ER stress pathways, partially recovered the BPA-induced cell apoptosis. In addition, an ROS scavenger attenuated the expression of the PERK/EIF2α/chop pathway-related proteins. Taken together, these data suggested that the ROS regulated PERK/EIF2α/chop pathway played a vital role in BPA-induced male reproductive toxicity.
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yin
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China; Medical Laboratory Technology Department, Chuxiong Medical College, Yunnan 675005, China.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Cui
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Liu
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Han
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ao
authors.initials: A
authors.lastname: Lin
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Cao
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China. Electronic address: jinyiliutmmu@163.com.
authors.forename: Jinyi
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001559:Benzhydryl Compounds / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D007248:Infertility, Male / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013737:Testis / Q000166:cytology / Q000187:drug effects; D051742:Transcription Factor CHOP / Q000378:metabolism*; D019892:eIF-2 Kinase / Q000378:metabolism*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D015852:Eukaryotic Initiation Factor-2; D010636:Phenols; D017382:Reactive Oxygen Species; D051742:Transcription Factor CHOP; D019892:eIF-2 Kinase; C497250:Ddit3 protein, mouse; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; Endoplasmic reticulum stress; Male reproductive toxicity; PERK/EIF2α/chop pathway