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 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. Ausführliche Beschreibung

Gespeichert in:

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]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	folliculogenesis oocyte epigenetic modification subfertility

Übergeordnetes Werk:	In: International Journal of Molecular Sciences - MDPI AG, 2003, 23(2022), 19, p 12008
Übergeordnetes Werk:	volume:23 ; year:2022 ; number:19, p 12008

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.3390/ijms231912008

Katalog-ID:	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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allfields	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
allfieldsGer	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
allfieldsSound	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
language	English
source	In International Journal of Molecular Sciences 23(2022), 19, p 12008 volume:23 year:2022 number:19, p 12008
sourceStr	In International Journal of Molecular Sciences 23(2022), 19, p 12008 volume:23 year:2022 number:19, p 12008
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	<i<Kdm2a</i< folliculogenesis oocyte epigenetic modification subfertility Biology (General) Chemistry
isfreeaccess_bool	true
container_title	International Journal of Molecular Sciences
authorswithroles_txt_mv	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@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	316340715
id	DOAJ084012617
language_de	englisch
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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. 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callnumber-first	Q - Science
author	Xianrong Xiong
spellingShingle	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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topic_title	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
topic	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
topic_unstemmed	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
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title	Oocyte-Specific Knockout of Histone Lysine Demethylase KDM2a Compromises Fertility by Blocking the Development of Follicles and Oocytes
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title_full	Oocyte-Specific Knockout of Histone Lysine Demethylase KDM2a Compromises Fertility by Blocking the Development of Follicles and Oocytes
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author_browse	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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title_sort	oocyte-specific knockout of histone lysine demethylase kdm2a compromises fertility by blocking the development of follicles and oocytes
callnumber	QH301-705.5
title_auth	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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title_short	Oocyte-Specific Knockout of Histone Lysine Demethylase KDM2a Compromises Fertility by Blocking the Development of Follicles and Oocytes
url	https://doi.org/10.3390/ijms231912008 https://doaj.org/article/5a78ca60c4694eb8859db8ee5f660fa7 https://www.mdpi.com/1422-0067/23/19/12008 https://doaj.org/toc/1661-6596 https://doaj.org/toc/1422-0067
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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.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a"><i<Kdm2a</i<</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">folliculogenesis</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">oocyte</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">epigenetic modification</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">subfertility</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Biology (General)</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Chemistry</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Xiaojian 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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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