Lack of Cytosolic Carboxypeptidase 1 Leads to Subfertility due to the Reduced Number of Antral Follicles in pcd3J-/- Females |
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Authors: | Ning Song Nameun Kim Rui Xiao Hojun Choi Hyo-Im Chun Min-Hee Kang Jin-Hoi Kim Kunho Seo Nagasundarapandian Soundrarajan Jeong-Tae Do Hyuk Song Zhao-Jia Ge Chankyu Park |
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Institution: | 1 Department of Animal Biotechnology, Konkuk University, Seoul, South Korea, ; 2 Colleges of Veterinary Medicine, Konkuk University, Seoul, South Korea, ; 3 College of Animal Science and Veterinary Medicine, Qingdao Agricultural University, Qingdao, P.R. China, ; Ottawa Hospital Research Institute and University of Ottawa, CANADA, |
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Abstract: | Females homozygous for the Purkinje cell degeneration mutation (pcd) are fertile, although the success rate is much lower than in the wild type. We performed detailed analysis of reproductive abnormalities of pcd females. The number of oocytes produced following exogenous gonadotropin treatment was much lower in pcd
3J-/- females than in pcd
3J+/+ females. Furthermore, the estrous cyclicity of pcd
3J-/- females according to the appearance of the vagina was almost undetectable comparing to that of the wild type. Histological analyses and follicle counting of 4- and 8-week-old pcd
3J-/- ovaries showed an increase in the number of secondary follicles and a decrease in the number of antral follicles, indicating that AGTPBP1/ CCP1 plays an important role in the development of secondary follicles into antral follicles. Consistent with a previous analysis of the pcd cerebellum, pcd
3J-/- ovaries also showed a clear increase in the level of polyglutamylation. Gene expression analysis showed that both oocytes and cumulus cells express CCP1. However, Ccp4 and CCP6, which can compensate the function of CCP1, were not expressed in mouse ovaries. Failure of microtubule deglutamylation did not affect the structure and function of the meiotic spindle in properly aligning chromosomes in the center of the nucleus during meiosis in pcd
3J-/- females. We also showed that the pituitary-derived growth and reproduction-related endocrine system functions normally in pcd
3J-/- mice. The results of this study provide insight into additional functions of CCP1, which cannot be fully explained by the side chain deglutamylation of microtubules alone. |
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