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| Status |
Public on Oct 29, 2023 |
| Title |
昼夜时钟蛋白NR1D1通过调节线粒体生物合成和脂质运输来控制颗粒细胞内分泌功能 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
With rapid economic and social development, people's living habits have changed dramatically. Long-term exposure to artificial light, shift work and staying up late have been found to seriously disrupt people's normal biological rhythms and impair female reproductive function, leading to increased rates of infertility and abortion. In this study, we established a mouse model of continuous light exposure to explore the effects of long-term environmental circadian disturbances on the reproductive endocrine function and related mechanisms in females. We found that continuous light exposure caused reproductive and endocrine metabolic abnormalities in female mice, including estrous cycle disorders, ovarian changes of increased unruptured luteinized cystic follicles, LH elevation and hyperandrogenism. Moreover, the circadian rhythm genes expression in follicular granulosa cells was disrupted, in particular the expression of Nr1d1 showed a significant increase at night. We further showed that the up-regulation of NR1D1 promoted the expression of mitochondrial biosynthesis protein PGC1α and lipid transport related proteins such as SLC27A6, CPT1α, etc, in granulosa cells, and activated the PTEN/PI3K/AKT signaling pathway, leading to premature luteinization of granulosa cells. In addition, the gap junctions between cumulus and oocytes were prematurely closed in COCs treated with NR1D1 agonist GSK4112, which impaired oocyte quality, resulting in reduced maturation, disordered spindle assembly and chromosome arrangement, mitochondrial dysfunction. In conclusion, the circadian clock protein NR1D1 plays an essential role in maintaining granulosa cell endocrine function and oocyte quality. The findings may provide fresh insights into how circadian rhythm disturbances caused by staying up late and continuous exposure to artificial light sources can damage female reproductive function.
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| Overall design |
To further investigate how elevated expression levels of NR1D1 are involved in affecting endocrine function in granulosa cells, we selected the NR1D1 agonist GSK4112 to treat follicular granulosa cells of female mice in vivo.
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| Citation missing |
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| Submission date |
Oct 29, 2023 |
| Last update date |
Oct 29, 2023 |
| Contact name |
Ou Xiang-Hong |
| E-mail(s) |
ouxh@gd2h.org.cn
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| Organization name |
Guangdong Second Provincial General Hospital
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| Street address |
Guangzhou
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| City |
Guangzhou |
| ZIP/Postal code |
510000 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA1033342 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE246496_fpkm.txt.gz |
842.3 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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