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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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE246496 | GEO | 2023/10/29

REPOSITORIES: GEO

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Project description:The goal of the experiment was to perform a large scale study of circadian regulation of gene expression in maize. To identify maize genes with expression regulated by the circadian clock, transcript levels in the aerial tissues of young maize seedlings were determined by transcriptional profiling with the Affymetrix GeneChip Maize Genome Array. Maize inbred B73 seedlings were grown inside Conviron growth chamber. B73 seedlings were grown for 7 days under 12 h light:12 h dark (LD) photocycles, 26° C temperature and 70% humidity. At the 8th day, seedlings were transferred to continuous light (LL) and were allowed to entrain completely for 24 h prior to tissue harvest following which tissue was harvested every 4 hours under LL conditions for a period of 48h. Therefore, for the circadian LL time course 12 time points were collected as follows (also defined as factors in the treatment section): ZT0 - 8:00 am/ subjective dawn/ Day1 ZT4 - 12:00 pm/ subjective mid-day/ Day1 ZT8 - 4:00 pm/ subjective late-day/ Day1 ZT12 - 8:00 pm/ subjective dusk/ Day1 ZT16 - 12:00 am/ subjective mid-night/ Day1 ZT20 - 4:00 am/ subjective pre-dawn/ Day1 ZT24- 8:00 am/ subjective dawn/ Day2 ZT28 - 12:00 pm/ subjective mid-day/ Day2 ZT32 - 4:00 pm/ subjective late-day/ Day2 ZT36 - 8:00 pm/ subjective dusk/ Day2 ZT40 - 12:00 am/ subjective mid-night/ Day2 ZT44 - 4:00 am/ subjective pre-dawn/ Day2 Tissue comprised of aerial portion of the seedlings (corresponding to tissue from the prop roots and up) for RNA isolation. Total RNA was isolated from the entire aerial portion of 7 day-old seedlings (corresponding to tissue from the prop roots and up) by Trizol extraction followed by Qiagen RNeasy columns and treatment with RNase-free DNase I (Qiagen; qiagen.com). RNA was isolated from 3 independent biological replicates was pooled. cRNA was generated from pooled total RNA from 3 biological replicates with the GeneChip One-Cycle Target Labeling kit according to the manufacturer’s recommendations (Affymetrix, affymetrix.com). The University of California, Berkeley Functional Genomics Laboratory hybridized samples to Affymetrix GeneChip Maize Genome Arrays and scanned the washed arrays as suggested by manufacturer. Probe sets called “Not Present” or “Marginal” on one or more microarrays were removed from the downstream analysis, as is common practice with circadian studies. Raw hybridization intensities were normalized across all twelve arrays using RMA express in Perfect Match mode. ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Frank G. Harmon. The equivalent experiment is ZM28 at PLEXdb.] Continuous Light: ZT0(1-replications); Continuous Light: ZT4(1-replications); Continuous Light: ZT8(1-replications); Continuous Light: ZT12(1-replications); Continuous Light: ZT16(1-replications); Continuous Light: ZT20(1-replications); Continuous Light: ZT24(1-replications); Continuous Light: ZT28(1-replications); Continuous Light: ZT32(1-replications); Continuous Light: ZT36(1-replications); Continuous Light: ZT40(1-replications); Continuous Light: ZT44(1-replications)

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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

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