PARP1-catalyzed PARylation of YY1 mediates endoplasmic reticulum stress in granulosa cells to determine primordial follicle activation
Abstract Although only a small number of primordial follicles are known to be selectively activated during female reproductive cycles, the mechanisms that trigger this recruitment remain largely uncharacterized. Misregulated activation of primordial follicles may lead to the exhaustion of the non-re...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-08-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-05984-w |
| _version_ | 1827590298731020288 |
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| author | Wei Chen Qiukai E Bo Sun Pengxue Zhang Nan Li Shujia Fei Yingnan Wang Shuting Liu Xiaoqiu Liu Xuesen Zhang |
| author_facet | Wei Chen Qiukai E Bo Sun Pengxue Zhang Nan Li Shujia Fei Yingnan Wang Shuting Liu Xiaoqiu Liu Xuesen Zhang |
| author_sort | Wei Chen |
| collection | DOAJ |
| description | Abstract Although only a small number of primordial follicles are known to be selectively activated during female reproductive cycles, the mechanisms that trigger this recruitment remain largely uncharacterized. Misregulated activation of primordial follicles may lead to the exhaustion of the non-renewable pool of primordial follicles, resulting in premature ovarian insufficiency. Here, we found that poly(ADP-ribose) polymerase 1 (PARP1) enzymatic activity in the surrounding granulosa cells (GCs) in follicles determines the subpopulation of the dormant primordial follicles to be awakened. Conversely, specifically inhibiting PARP1 in oocytes in an in vitro mouse follicle reconstitution model does not affect primordial follicle activation. Further analysis revealed that PARP1-catalyzed transcription factor YY1 PARylation at Y185 residue facilitates YY1 occupancy at Grp78 promoter, a key molecular chaperone of endoplasmic reticulum stress (ERS), and promotes Grp78 transcription in GCs, which is required for GCs maintaining proper ERS during primordial follicle activation. Inhibiting PARP1 prevents the loss of primordial follicle pool by attenuating the excessive ERS in GCs under fetal bisphenol A exposure. Together, we demonstrate that PARP1 in GCs acts as a pivotal modulator to determine the fate of the primordial follicles and may represent a novel therapeutic target for the retention of primordial follicle pool in females. |
| first_indexed | 2024-03-09T01:14:56Z |
| format | Article |
| id | doaj.art-b15e0d063cd442dc8a1c3f06c70f5456 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-03-09T01:14:56Z |
| publishDate | 2023-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-b15e0d063cd442dc8a1c3f06c70f54562023-12-10T12:33:23ZengNature Publishing GroupCell Death and Disease2041-48892023-08-0114811410.1038/s41419-023-05984-wPARP1-catalyzed PARylation of YY1 mediates endoplasmic reticulum stress in granulosa cells to determine primordial follicle activationWei Chen0Qiukai E1Bo Sun2Pengxue Zhang3Nan Li4Shujia Fei5Yingnan Wang6Shuting Liu7Xiaoqiu Liu8Xuesen Zhang9State Key Laboratory of Reproductive Medicine, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine, Nanjing Medical UniversityDepartment of Pathogen Biology, College of Basic Medical Sciences, China Medical UniversityKey Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical UniversityAbstract Although only a small number of primordial follicles are known to be selectively activated during female reproductive cycles, the mechanisms that trigger this recruitment remain largely uncharacterized. Misregulated activation of primordial follicles may lead to the exhaustion of the non-renewable pool of primordial follicles, resulting in premature ovarian insufficiency. Here, we found that poly(ADP-ribose) polymerase 1 (PARP1) enzymatic activity in the surrounding granulosa cells (GCs) in follicles determines the subpopulation of the dormant primordial follicles to be awakened. Conversely, specifically inhibiting PARP1 in oocytes in an in vitro mouse follicle reconstitution model does not affect primordial follicle activation. Further analysis revealed that PARP1-catalyzed transcription factor YY1 PARylation at Y185 residue facilitates YY1 occupancy at Grp78 promoter, a key molecular chaperone of endoplasmic reticulum stress (ERS), and promotes Grp78 transcription in GCs, which is required for GCs maintaining proper ERS during primordial follicle activation. Inhibiting PARP1 prevents the loss of primordial follicle pool by attenuating the excessive ERS in GCs under fetal bisphenol A exposure. Together, we demonstrate that PARP1 in GCs acts as a pivotal modulator to determine the fate of the primordial follicles and may represent a novel therapeutic target for the retention of primordial follicle pool in females.https://doi.org/10.1038/s41419-023-05984-w |
| spellingShingle | Wei Chen Qiukai E Bo Sun Pengxue Zhang Nan Li Shujia Fei Yingnan Wang Shuting Liu Xiaoqiu Liu Xuesen Zhang PARP1-catalyzed PARylation of YY1 mediates endoplasmic reticulum stress in granulosa cells to determine primordial follicle activation Cell Death and Disease |
| title | PARP1-catalyzed PARylation of YY1 mediates endoplasmic reticulum stress in granulosa cells to determine primordial follicle activation |
| title_full | PARP1-catalyzed PARylation of YY1 mediates endoplasmic reticulum stress in granulosa cells to determine primordial follicle activation |
| title_fullStr | PARP1-catalyzed PARylation of YY1 mediates endoplasmic reticulum stress in granulosa cells to determine primordial follicle activation |
| title_full_unstemmed | PARP1-catalyzed PARylation of YY1 mediates endoplasmic reticulum stress in granulosa cells to determine primordial follicle activation |
| title_short | PARP1-catalyzed PARylation of YY1 mediates endoplasmic reticulum stress in granulosa cells to determine primordial follicle activation |
| title_sort | parp1 catalyzed parylation of yy1 mediates endoplasmic reticulum stress in granulosa cells to determine primordial follicle activation |
| url | https://doi.org/10.1038/s41419-023-05984-w |
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