Oocyte-Specific Knockout of Histone Lysine Demethylase KDM2a Compromises Fertility by Blocking the Development of Follicles and Oocytes
The methylation status of histones plays a crucial role in many cellular processes, including follicular and oocyte development. Lysine-specific demethylase 2a (KDM2a) has been reported to be closely associated with gametogenesis and reproductive performance, but the specific function and regulatory...
Ausführliche Beschreibung
Autor*in: |
Xianrong Xiong [verfasserIn] Xiaojian Zhang [verfasserIn] Manzhen Yang [verfasserIn] Yanjin Zhu [verfasserIn] Hailing Yu [verfasserIn] Xixi Fei [verfasserIn] Fuko Mastuda [verfasserIn] Daoliang Lan [verfasserIn] Yan Xiong [verfasserIn] Wei Fu [verfasserIn] Shi Yin [verfasserIn] Jian Li [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
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2022 |
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In: International Journal of Molecular Sciences - MDPI AG, 2003, 23(2022), 19, p 12008 |
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volume:23 ; year:2022 ; number:19, p 12008 |
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DOI / URN: |
10.3390/ijms231912008 |
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DOAJ084012617 |
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245 | 1 | 0 | |a Oocyte-Specific Knockout of Histone Lysine Demethylase KDM2a Compromises Fertility by Blocking the Development of Follicles and Oocytes |
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520 | |a The methylation status of histones plays a crucial role in many cellular processes, including follicular and oocyte development. Lysine-specific demethylase 2a (KDM2a) has been reported to be closely associated with gametogenesis and reproductive performance, but the specific function and regulatory mechanism have been poorly characterized in vivo. We found KDM2a to be highly expressed in growing follicles and oocytes of mice in this study. To elucidate the physiological role of <i<Kdm2a</i<, the zona pellucida 3-Cre (<i<Zp3</i<-<i<Cre</i<)/LoxP system was used to generate an oocyte <i<Kdm2a</i< conditional knockout (<i<Zp3</i<-<i<Cre</i<; <i<Kdm2a<sup<flox/flox</sup<</i<, termed <i<Kdm2a</i< cKO) model. Our results showed that the number of pups was reduced by approximately 50% in adult <i<Kdm2a</i< cKO female mice mating with wildtype males than that of the control (<i<Kdm2a<sup<flox/flox</sup<</i<) group. To analyze the potential causes, the ovaries of <i<Kdm2a</i< cKO mice were subjected to histological examination, and results indicated an obvious difference in follicular development between <i<Kdm2a</i< cKO and control female mice and partial arrest at the primary antral follicle stage. The GVBD and matured rates of oocytes were also compromised after conditional knockout <i<Kdm2a</i<, and the morphological abnormal oocytes increased. Furthermore, the level of 17β-estradiol of <i<Kdm2a</i< cKO mice was only 60% of that in the counterparts, and hormone sensitivity decreased as the total number of ovulated and matured oocytes decreased after superovulation. After deletion of <i<Kdm2a</i<, the patterns of H3K36me2/3 in GVBD-stage oocytes were remarkedly changed. Transcriptome sequencing showed that the mRNA expression profiles in <i<Kdm2a</i< cKO oocytes were significantly different, and numerous differentially expressed genes were involved in pathways regulating follicular and oocyte development. Taken together, these results indicated that the oocyte-specific knockout <i<Kdm2a</i< gene led to female subfertility, suggesting the crucial role of <i<Kdm2a</i< in epigenetic modification and follicular and oocyte development. | ||
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700 | 0 | |a Jian Li |e verfasserin |4 aut | |
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10.3390/ijms231912008 doi (DE-627)DOAJ084012617 (DE-599)DOAJ5a78ca60c4694eb8859db8ee5f660fa7 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Xianrong Xiong verfasserin aut Oocyte-Specific Knockout of Histone Lysine Demethylase KDM2a Compromises Fertility by Blocking the Development of Follicles and Oocytes 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The methylation status of histones plays a crucial role in many cellular processes, including follicular and oocyte development. Lysine-specific demethylase 2a (KDM2a) has been reported to be closely associated with gametogenesis and reproductive performance, but the specific function and regulatory mechanism have been poorly characterized in vivo. We found KDM2a to be highly expressed in growing follicles and oocytes of mice in this study. To elucidate the physiological role of <i<Kdm2a</i<, the zona pellucida 3-Cre (<i<Zp3</i<-<i<Cre</i<)/LoxP system was used to generate an oocyte <i<Kdm2a</i< conditional knockout (<i<Zp3</i<-<i<Cre</i<; <i<Kdm2a<sup<flox/flox</sup<</i<, termed <i<Kdm2a</i< cKO) model. Our results showed that the number of pups was reduced by approximately 50% in adult <i<Kdm2a</i< cKO female mice mating with wildtype males than that of the control (<i<Kdm2a<sup<flox/flox</sup<</i<) group. To analyze the potential causes, the ovaries of <i<Kdm2a</i< cKO mice were subjected to histological examination, and results indicated an obvious difference in follicular development between <i<Kdm2a</i< cKO and control female mice and partial arrest at the primary antral follicle stage. The GVBD and matured rates of oocytes were also compromised after conditional knockout <i<Kdm2a</i<, and the morphological abnormal oocytes increased. Furthermore, the level of 17β-estradiol of <i<Kdm2a</i< cKO mice was only 60% of that in the counterparts, and hormone sensitivity decreased as the total number of ovulated and matured oocytes decreased after superovulation. After deletion of <i<Kdm2a</i<, the patterns of H3K36me2/3 in GVBD-stage oocytes were remarkedly changed. Transcriptome sequencing showed that the mRNA expression profiles in <i<Kdm2a</i< cKO oocytes were significantly different, and numerous differentially expressed genes were involved in pathways regulating follicular and oocyte development. Taken together, these results indicated that the oocyte-specific knockout <i<Kdm2a</i< gene led to female subfertility, suggesting the crucial role of <i<Kdm2a</i< in epigenetic modification and follicular and oocyte development. <i<Kdm2a</i< folliculogenesis oocyte epigenetic modification subfertility Biology (General) Chemistry Xiaojian Zhang verfasserin aut Manzhen Yang verfasserin aut Yanjin Zhu verfasserin aut Hailing Yu verfasserin aut Xixi Fei verfasserin aut Fuko Mastuda verfasserin aut Daoliang Lan verfasserin aut Yan Xiong verfasserin aut Wei Fu verfasserin aut Shi Yin verfasserin aut Jian Li verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 19, p 12008 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:19, p 12008 https://doi.org/10.3390/ijms231912008 kostenfrei https://doaj.org/article/5a78ca60c4694eb8859db8ee5f660fa7 kostenfrei https://www.mdpi.com/1422-0067/23/19/12008 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 19, p 12008 |
spelling |
10.3390/ijms231912008 doi (DE-627)DOAJ084012617 (DE-599)DOAJ5a78ca60c4694eb8859db8ee5f660fa7 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Xianrong Xiong verfasserin aut Oocyte-Specific Knockout of Histone Lysine Demethylase KDM2a Compromises Fertility by Blocking the Development of Follicles and Oocytes 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The methylation status of histones plays a crucial role in many cellular processes, including follicular and oocyte development. Lysine-specific demethylase 2a (KDM2a) has been reported to be closely associated with gametogenesis and reproductive performance, but the specific function and regulatory mechanism have been poorly characterized in vivo. We found KDM2a to be highly expressed in growing follicles and oocytes of mice in this study. To elucidate the physiological role of <i<Kdm2a</i<, the zona pellucida 3-Cre (<i<Zp3</i<-<i<Cre</i<)/LoxP system was used to generate an oocyte <i<Kdm2a</i< conditional knockout (<i<Zp3</i<-<i<Cre</i<; <i<Kdm2a<sup<flox/flox</sup<</i<, termed <i<Kdm2a</i< cKO) model. Our results showed that the number of pups was reduced by approximately 50% in adult <i<Kdm2a</i< cKO female mice mating with wildtype males than that of the control (<i<Kdm2a<sup<flox/flox</sup<</i<) group. To analyze the potential causes, the ovaries of <i<Kdm2a</i< cKO mice were subjected to histological examination, and results indicated an obvious difference in follicular development between <i<Kdm2a</i< cKO and control female mice and partial arrest at the primary antral follicle stage. The GVBD and matured rates of oocytes were also compromised after conditional knockout <i<Kdm2a</i<, and the morphological abnormal oocytes increased. Furthermore, the level of 17β-estradiol of <i<Kdm2a</i< cKO mice was only 60% of that in the counterparts, and hormone sensitivity decreased as the total number of ovulated and matured oocytes decreased after superovulation. After deletion of <i<Kdm2a</i<, the patterns of H3K36me2/3 in GVBD-stage oocytes were remarkedly changed. Transcriptome sequencing showed that the mRNA expression profiles in <i<Kdm2a</i< cKO oocytes were significantly different, and numerous differentially expressed genes were involved in pathways regulating follicular and oocyte development. Taken together, these results indicated that the oocyte-specific knockout <i<Kdm2a</i< gene led to female subfertility, suggesting the crucial role of <i<Kdm2a</i< in epigenetic modification and follicular and oocyte development. <i<Kdm2a</i< folliculogenesis oocyte epigenetic modification subfertility Biology (General) Chemistry Xiaojian Zhang verfasserin aut Manzhen Yang verfasserin aut Yanjin Zhu verfasserin aut Hailing Yu verfasserin aut Xixi Fei verfasserin aut Fuko Mastuda verfasserin aut Daoliang Lan verfasserin aut Yan Xiong verfasserin aut Wei Fu verfasserin aut Shi Yin verfasserin aut Jian Li verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 19, p 12008 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:19, p 12008 https://doi.org/10.3390/ijms231912008 kostenfrei https://doaj.org/article/5a78ca60c4694eb8859db8ee5f660fa7 kostenfrei https://www.mdpi.com/1422-0067/23/19/12008 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 19, p 12008 |
allfields_unstemmed |
10.3390/ijms231912008 doi (DE-627)DOAJ084012617 (DE-599)DOAJ5a78ca60c4694eb8859db8ee5f660fa7 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Xianrong Xiong verfasserin aut Oocyte-Specific Knockout of Histone Lysine Demethylase KDM2a Compromises Fertility by Blocking the Development of Follicles and Oocytes 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The methylation status of histones plays a crucial role in many cellular processes, including follicular and oocyte development. Lysine-specific demethylase 2a (KDM2a) has been reported to be closely associated with gametogenesis and reproductive performance, but the specific function and regulatory mechanism have been poorly characterized in vivo. We found KDM2a to be highly expressed in growing follicles and oocytes of mice in this study. To elucidate the physiological role of <i<Kdm2a</i<, the zona pellucida 3-Cre (<i<Zp3</i<-<i<Cre</i<)/LoxP system was used to generate an oocyte <i<Kdm2a</i< conditional knockout (<i<Zp3</i<-<i<Cre</i<; <i<Kdm2a<sup<flox/flox</sup<</i<, termed <i<Kdm2a</i< cKO) model. Our results showed that the number of pups was reduced by approximately 50% in adult <i<Kdm2a</i< cKO female mice mating with wildtype males than that of the control (<i<Kdm2a<sup<flox/flox</sup<</i<) group. To analyze the potential causes, the ovaries of <i<Kdm2a</i< cKO mice were subjected to histological examination, and results indicated an obvious difference in follicular development between <i<Kdm2a</i< cKO and control female mice and partial arrest at the primary antral follicle stage. The GVBD and matured rates of oocytes were also compromised after conditional knockout <i<Kdm2a</i<, and the morphological abnormal oocytes increased. Furthermore, the level of 17β-estradiol of <i<Kdm2a</i< cKO mice was only 60% of that in the counterparts, and hormone sensitivity decreased as the total number of ovulated and matured oocytes decreased after superovulation. After deletion of <i<Kdm2a</i<, the patterns of H3K36me2/3 in GVBD-stage oocytes were remarkedly changed. Transcriptome sequencing showed that the mRNA expression profiles in <i<Kdm2a</i< cKO oocytes were significantly different, and numerous differentially expressed genes were involved in pathways regulating follicular and oocyte development. Taken together, these results indicated that the oocyte-specific knockout <i<Kdm2a</i< gene led to female subfertility, suggesting the crucial role of <i<Kdm2a</i< in epigenetic modification and follicular and oocyte development. <i<Kdm2a</i< folliculogenesis oocyte epigenetic modification subfertility Biology (General) Chemistry Xiaojian Zhang verfasserin aut Manzhen Yang verfasserin aut Yanjin Zhu verfasserin aut Hailing Yu verfasserin aut Xixi Fei verfasserin aut Fuko Mastuda verfasserin aut Daoliang Lan verfasserin aut Yan Xiong verfasserin aut Wei Fu verfasserin aut Shi Yin verfasserin aut Jian Li verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 19, p 12008 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:19, p 12008 https://doi.org/10.3390/ijms231912008 kostenfrei https://doaj.org/article/5a78ca60c4694eb8859db8ee5f660fa7 kostenfrei https://www.mdpi.com/1422-0067/23/19/12008 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 19, p 12008 |
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10.3390/ijms231912008 doi (DE-627)DOAJ084012617 (DE-599)DOAJ5a78ca60c4694eb8859db8ee5f660fa7 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Xianrong Xiong verfasserin aut Oocyte-Specific Knockout of Histone Lysine Demethylase KDM2a Compromises Fertility by Blocking the Development of Follicles and Oocytes 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The methylation status of histones plays a crucial role in many cellular processes, including follicular and oocyte development. Lysine-specific demethylase 2a (KDM2a) has been reported to be closely associated with gametogenesis and reproductive performance, but the specific function and regulatory mechanism have been poorly characterized in vivo. We found KDM2a to be highly expressed in growing follicles and oocytes of mice in this study. To elucidate the physiological role of <i<Kdm2a</i<, the zona pellucida 3-Cre (<i<Zp3</i<-<i<Cre</i<)/LoxP system was used to generate an oocyte <i<Kdm2a</i< conditional knockout (<i<Zp3</i<-<i<Cre</i<; <i<Kdm2a<sup<flox/flox</sup<</i<, termed <i<Kdm2a</i< cKO) model. Our results showed that the number of pups was reduced by approximately 50% in adult <i<Kdm2a</i< cKO female mice mating with wildtype males than that of the control (<i<Kdm2a<sup<flox/flox</sup<</i<) group. To analyze the potential causes, the ovaries of <i<Kdm2a</i< cKO mice were subjected to histological examination, and results indicated an obvious difference in follicular development between <i<Kdm2a</i< cKO and control female mice and partial arrest at the primary antral follicle stage. The GVBD and matured rates of oocytes were also compromised after conditional knockout <i<Kdm2a</i<, and the morphological abnormal oocytes increased. Furthermore, the level of 17β-estradiol of <i<Kdm2a</i< cKO mice was only 60% of that in the counterparts, and hormone sensitivity decreased as the total number of ovulated and matured oocytes decreased after superovulation. After deletion of <i<Kdm2a</i<, the patterns of H3K36me2/3 in GVBD-stage oocytes were remarkedly changed. Transcriptome sequencing showed that the mRNA expression profiles in <i<Kdm2a</i< cKO oocytes were significantly different, and numerous differentially expressed genes were involved in pathways regulating follicular and oocyte development. Taken together, these results indicated that the oocyte-specific knockout <i<Kdm2a</i< gene led to female subfertility, suggesting the crucial role of <i<Kdm2a</i< in epigenetic modification and follicular and oocyte development. <i<Kdm2a</i< folliculogenesis oocyte epigenetic modification subfertility Biology (General) Chemistry Xiaojian Zhang verfasserin aut Manzhen Yang verfasserin aut Yanjin Zhu verfasserin aut Hailing Yu verfasserin aut Xixi Fei verfasserin aut Fuko Mastuda verfasserin aut Daoliang Lan verfasserin aut Yan Xiong verfasserin aut Wei Fu verfasserin aut Shi Yin verfasserin aut Jian Li verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 19, p 12008 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:19, p 12008 https://doi.org/10.3390/ijms231912008 kostenfrei https://doaj.org/article/5a78ca60c4694eb8859db8ee5f660fa7 kostenfrei https://www.mdpi.com/1422-0067/23/19/12008 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 19, p 12008 |
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10.3390/ijms231912008 doi (DE-627)DOAJ084012617 (DE-599)DOAJ5a78ca60c4694eb8859db8ee5f660fa7 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Xianrong Xiong verfasserin aut Oocyte-Specific Knockout of Histone Lysine Demethylase KDM2a Compromises Fertility by Blocking the Development of Follicles and Oocytes 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The methylation status of histones plays a crucial role in many cellular processes, including follicular and oocyte development. Lysine-specific demethylase 2a (KDM2a) has been reported to be closely associated with gametogenesis and reproductive performance, but the specific function and regulatory mechanism have been poorly characterized in vivo. We found KDM2a to be highly expressed in growing follicles and oocytes of mice in this study. To elucidate the physiological role of <i<Kdm2a</i<, the zona pellucida 3-Cre (<i<Zp3</i<-<i<Cre</i<)/LoxP system was used to generate an oocyte <i<Kdm2a</i< conditional knockout (<i<Zp3</i<-<i<Cre</i<; <i<Kdm2a<sup<flox/flox</sup<</i<, termed <i<Kdm2a</i< cKO) model. Our results showed that the number of pups was reduced by approximately 50% in adult <i<Kdm2a</i< cKO female mice mating with wildtype males than that of the control (<i<Kdm2a<sup<flox/flox</sup<</i<) group. To analyze the potential causes, the ovaries of <i<Kdm2a</i< cKO mice were subjected to histological examination, and results indicated an obvious difference in follicular development between <i<Kdm2a</i< cKO and control female mice and partial arrest at the primary antral follicle stage. The GVBD and matured rates of oocytes were also compromised after conditional knockout <i<Kdm2a</i<, and the morphological abnormal oocytes increased. Furthermore, the level of 17β-estradiol of <i<Kdm2a</i< cKO mice was only 60% of that in the counterparts, and hormone sensitivity decreased as the total number of ovulated and matured oocytes decreased after superovulation. After deletion of <i<Kdm2a</i<, the patterns of H3K36me2/3 in GVBD-stage oocytes were remarkedly changed. Transcriptome sequencing showed that the mRNA expression profiles in <i<Kdm2a</i< cKO oocytes were significantly different, and numerous differentially expressed genes were involved in pathways regulating follicular and oocyte development. Taken together, these results indicated that the oocyte-specific knockout <i<Kdm2a</i< gene led to female subfertility, suggesting the crucial role of <i<Kdm2a</i< in epigenetic modification and follicular and oocyte development. <i<Kdm2a</i< folliculogenesis oocyte epigenetic modification subfertility Biology (General) Chemistry Xiaojian Zhang verfasserin aut Manzhen Yang verfasserin aut Yanjin Zhu verfasserin aut Hailing Yu verfasserin aut Xixi Fei verfasserin aut Fuko Mastuda verfasserin aut Daoliang Lan verfasserin aut Yan Xiong verfasserin aut Wei Fu verfasserin aut Shi Yin verfasserin aut Jian Li verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 19, p 12008 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:19, p 12008 https://doi.org/10.3390/ijms231912008 kostenfrei https://doaj.org/article/5a78ca60c4694eb8859db8ee5f660fa7 kostenfrei https://www.mdpi.com/1422-0067/23/19/12008 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 19, p 12008 |
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Xianrong Xiong @@aut@@ Xiaojian Zhang @@aut@@ Manzhen Yang @@aut@@ Yanjin Zhu @@aut@@ Hailing Yu @@aut@@ Xixi Fei @@aut@@ Fuko Mastuda @@aut@@ Daoliang Lan @@aut@@ Yan Xiong @@aut@@ Wei Fu @@aut@@ Shi Yin @@aut@@ Jian Li @@aut@@ |
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Xianrong Xiong misc QH301-705.5 misc QD1-999 misc <i<Kdm2a</i< misc folliculogenesis misc oocyte misc epigenetic modification misc subfertility misc Biology (General) misc Chemistry Oocyte-Specific Knockout of Histone Lysine Demethylase KDM2a Compromises Fertility by Blocking the Development of Follicles and Oocytes |
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QH301-705.5 QD1-999 Oocyte-Specific Knockout of Histone Lysine Demethylase KDM2a Compromises Fertility by Blocking the Development of Follicles and Oocytes <i<Kdm2a</i< folliculogenesis oocyte epigenetic modification subfertility |
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Oocyte-Specific Knockout of Histone Lysine Demethylase KDM2a Compromises Fertility by Blocking the Development of Follicles and Oocytes |
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Xianrong Xiong Xiaojian Zhang Manzhen Yang Yanjin Zhu Hailing Yu Xixi Fei Fuko Mastuda Daoliang Lan Yan Xiong Wei Fu Shi Yin Jian Li |
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oocyte-specific knockout of histone lysine demethylase kdm2a compromises fertility by blocking the development of follicles and oocytes |
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Oocyte-Specific Knockout of Histone Lysine Demethylase KDM2a Compromises Fertility by Blocking the Development of Follicles and Oocytes |
abstract |
The methylation status of histones plays a crucial role in many cellular processes, including follicular and oocyte development. Lysine-specific demethylase 2a (KDM2a) has been reported to be closely associated with gametogenesis and reproductive performance, but the specific function and regulatory mechanism have been poorly characterized in vivo. We found KDM2a to be highly expressed in growing follicles and oocytes of mice in this study. To elucidate the physiological role of <i<Kdm2a</i<, the zona pellucida 3-Cre (<i<Zp3</i<-<i<Cre</i<)/LoxP system was used to generate an oocyte <i<Kdm2a</i< conditional knockout (<i<Zp3</i<-<i<Cre</i<; <i<Kdm2a<sup<flox/flox</sup<</i<, termed <i<Kdm2a</i< cKO) model. Our results showed that the number of pups was reduced by approximately 50% in adult <i<Kdm2a</i< cKO female mice mating with wildtype males than that of the control (<i<Kdm2a<sup<flox/flox</sup<</i<) group. To analyze the potential causes, the ovaries of <i<Kdm2a</i< cKO mice were subjected to histological examination, and results indicated an obvious difference in follicular development between <i<Kdm2a</i< cKO and control female mice and partial arrest at the primary antral follicle stage. The GVBD and matured rates of oocytes were also compromised after conditional knockout <i<Kdm2a</i<, and the morphological abnormal oocytes increased. Furthermore, the level of 17β-estradiol of <i<Kdm2a</i< cKO mice was only 60% of that in the counterparts, and hormone sensitivity decreased as the total number of ovulated and matured oocytes decreased after superovulation. After deletion of <i<Kdm2a</i<, the patterns of H3K36me2/3 in GVBD-stage oocytes were remarkedly changed. Transcriptome sequencing showed that the mRNA expression profiles in <i<Kdm2a</i< cKO oocytes were significantly different, and numerous differentially expressed genes were involved in pathways regulating follicular and oocyte development. Taken together, these results indicated that the oocyte-specific knockout <i<Kdm2a</i< gene led to female subfertility, suggesting the crucial role of <i<Kdm2a</i< in epigenetic modification and follicular and oocyte development. |
abstractGer |
The methylation status of histones plays a crucial role in many cellular processes, including follicular and oocyte development. Lysine-specific demethylase 2a (KDM2a) has been reported to be closely associated with gametogenesis and reproductive performance, but the specific function and regulatory mechanism have been poorly characterized in vivo. We found KDM2a to be highly expressed in growing follicles and oocytes of mice in this study. To elucidate the physiological role of <i<Kdm2a</i<, the zona pellucida 3-Cre (<i<Zp3</i<-<i<Cre</i<)/LoxP system was used to generate an oocyte <i<Kdm2a</i< conditional knockout (<i<Zp3</i<-<i<Cre</i<; <i<Kdm2a<sup<flox/flox</sup<</i<, termed <i<Kdm2a</i< cKO) model. Our results showed that the number of pups was reduced by approximately 50% in adult <i<Kdm2a</i< cKO female mice mating with wildtype males than that of the control (<i<Kdm2a<sup<flox/flox</sup<</i<) group. To analyze the potential causes, the ovaries of <i<Kdm2a</i< cKO mice were subjected to histological examination, and results indicated an obvious difference in follicular development between <i<Kdm2a</i< cKO and control female mice and partial arrest at the primary antral follicle stage. The GVBD and matured rates of oocytes were also compromised after conditional knockout <i<Kdm2a</i<, and the morphological abnormal oocytes increased. Furthermore, the level of 17β-estradiol of <i<Kdm2a</i< cKO mice was only 60% of that in the counterparts, and hormone sensitivity decreased as the total number of ovulated and matured oocytes decreased after superovulation. After deletion of <i<Kdm2a</i<, the patterns of H3K36me2/3 in GVBD-stage oocytes were remarkedly changed. Transcriptome sequencing showed that the mRNA expression profiles in <i<Kdm2a</i< cKO oocytes were significantly different, and numerous differentially expressed genes were involved in pathways regulating follicular and oocyte development. Taken together, these results indicated that the oocyte-specific knockout <i<Kdm2a</i< gene led to female subfertility, suggesting the crucial role of <i<Kdm2a</i< in epigenetic modification and follicular and oocyte development. |
abstract_unstemmed |
The methylation status of histones plays a crucial role in many cellular processes, including follicular and oocyte development. Lysine-specific demethylase 2a (KDM2a) has been reported to be closely associated with gametogenesis and reproductive performance, but the specific function and regulatory mechanism have been poorly characterized in vivo. We found KDM2a to be highly expressed in growing follicles and oocytes of mice in this study. To elucidate the physiological role of <i<Kdm2a</i<, the zona pellucida 3-Cre (<i<Zp3</i<-<i<Cre</i<)/LoxP system was used to generate an oocyte <i<Kdm2a</i< conditional knockout (<i<Zp3</i<-<i<Cre</i<; <i<Kdm2a<sup<flox/flox</sup<</i<, termed <i<Kdm2a</i< cKO) model. Our results showed that the number of pups was reduced by approximately 50% in adult <i<Kdm2a</i< cKO female mice mating with wildtype males than that of the control (<i<Kdm2a<sup<flox/flox</sup<</i<) group. To analyze the potential causes, the ovaries of <i<Kdm2a</i< cKO mice were subjected to histological examination, and results indicated an obvious difference in follicular development between <i<Kdm2a</i< cKO and control female mice and partial arrest at the primary antral follicle stage. The GVBD and matured rates of oocytes were also compromised after conditional knockout <i<Kdm2a</i<, and the morphological abnormal oocytes increased. Furthermore, the level of 17β-estradiol of <i<Kdm2a</i< cKO mice was only 60% of that in the counterparts, and hormone sensitivity decreased as the total number of ovulated and matured oocytes decreased after superovulation. After deletion of <i<Kdm2a</i<, the patterns of H3K36me2/3 in GVBD-stage oocytes were remarkedly changed. Transcriptome sequencing showed that the mRNA expression profiles in <i<Kdm2a</i< cKO oocytes were significantly different, and numerous differentially expressed genes were involved in pathways regulating follicular and oocyte development. Taken together, these results indicated that the oocyte-specific knockout <i<Kdm2a</i< gene led to female subfertility, suggesting the crucial role of <i<Kdm2a</i< in epigenetic modification and follicular and oocyte development. |
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Oocyte-Specific Knockout of Histone Lysine Demethylase KDM2a Compromises Fertility by Blocking the Development of Follicles and Oocytes |
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