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Chronic cadmium exposure causes oocyte meiotic arrest by disrupting spindle assembly checkpoint and maturation promoting factor
Institution:1. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, PR China;2. College of Life Science, Shanxi University, Taiyuan, Shanxi, 030006, PR China;3. Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, 65211, USA;4. Fertility Preservation Lab, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, 510317, PR China;1. College of Life Science, Hunan University of Science and Technology, Xiangtan, Hunan, 411201, China;2. Department of Basic Medicine, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China;3. The Reproductive Medical Center of Nanning Second People''s Hospital, Nanning, Guangxi, 530031, China;4. College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, China;5. Department of Gynaecology and Obstetrics, The Affiliated Xiang-An Hospital of Xiamen University, Xiamen, Fujian, 361102, China;6. College of Biology and Agriculture (College of Food Science and Technology), Zunyi Normal College, Zunyi, 563006, China;7. Department of Gynaecology and Obstetrics, The Affiliated Zhong-Shan Hospital of Xiamen University, Xiamen, Fujian, 361004, China;1. State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Guangxi University, Nanning, Guangxi 530004, China;2. College of Animal Science & Technology, Guangxi University, Nanning, Guangxi 530004, China
Abstract:Cadmium (Cd) is a bioaccumulative heavy metal element with potential toxicity on the female reproductive system, but the exact molecular mechanisms have not yet been clearly defined. In this study, female mice were exposed to 0.5 mg/kg/day of CdCl2 for 60 consecutive days. We found that chronic Cd exposure significantly decreased the fecundity of female mice by affecting oocyte meiotic progression as indicated by disrupted spindle assembly, chromosome alignment and kinetochore-microtubule attachments, consequently resulting in aneuploid oocytes. Further studies showed that the periodic fluctuations of MPF activity and cyclin B1 expression were disturbed in Cd-exposed oocytes probably by affecting the spindle assembly checkpoint protein Bub3. In addition, Cd exposure induced oxidative stress as indicated by an increased level of reactive oxygen species and apoptosis in oocytes, leading to oocyte quality deterioration. Taken together, these data suggest that Cd exposure causes disrupted molecular events of meiotic progression and deterioration of oocyte quality via oxidative stress, leading to decrease of female fertility.
Keywords:Cadmium  Oocyte maturation  Fertilization  Oxidative stress
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