title: Expression of calmodulin in germ cells is associated with fenvalerate-induced male reproductive toxicity.
abstract: Exposure to fenvalerate was demonstrated to be toxic to the male reproductive system. Our previous data revealed that intracellular calcium plays an important role in regulating the above toxicity, through actions on both T-type calcium channels and endoplasmic reticulum calcium signals. The present study explored the effects of fenvalerate on the expression of calmodulin in mouse testis and GC-2spd(ts) cells, and its association with fenvalerate-induced male reproductive toxicity. Male mice were subjected to different doses (3.71, 18.56, 37.12, 92.81 mg/kg bw) of fenvalerate or vehicle control for 4 weeks. Expression of calmodulin was determined by real-time polymerase chain reaction (PCR) and Western blot analysis in mouse testis. Similar approaches were utilized in GC-2spd(ts) cells cultured with 5 μM fenvalerate at different time points. In the in vivo study, all mice survived through the entire 4 weeks. Administration of fenvalerate resulted in a dose-dependent reduction in testis weight/body weight, sperm motility, and increased head abnormality rate. By histological staining, mice treated with fenvalerate at higher doses showed dilated seminiferous tubules and disturbed arrangement of spermatogenic cells. Meanwhile, both mRNA and protein expression of calmodulin were significantly increased in the testes of mice exposed to fenvalerate compared to control mice. Moreover, in the in vitro study, 5 μM fenvalerate significantly increased the expression of calmodulin at the mRNA and protein levels in GC-2spd(ts) cells after 8 h of incubation and sustained these levels for at least 24 h. Collectively, these data suggested that enhanced expression of calmodulin correlates with male reproductive damage induced by fenvalerate.
authors.affiliation: Department of Toxicology and Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Gao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Changsong
authors.initials: C
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Lu
authors.forename: Rong
authors.initials: R
authors.lastname: Gao
authors.forename: Fei
authors.initials: F
authors.lastname: Huan
authors.forename: Darlene
authors.initials: D
authors.lastname: Dixon
authors.forename: Hang
authors.initials: H
authors.lastname: Xiao
mesh_terms: D000818:Animals; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007248:Infertility, Male / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009570:Nitriles / Q000008:administration & dosage / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010575:Pesticides / Q000633:toxicity*; D010865:Pilot Projects; D011722:Pyrethrins / Q000008:administration & dosage / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D013081:Sperm Motility / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D013737:Testis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002147:Calmodulin; D009570:Nitriles; D010575:Pesticides; D011722:Pyrethrins; D012333:RNA, Messenger; C017690:fenvalerate