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Genome-wide maps of chromatin state in Wild Type mouse ovary

ABSTRACT: Primary ovarian insufficiency (POI) is a clinical syndrome of ovarian dysfunction characterized by premature exhaustion of primordial follicles. POI causes infertility, serious daily life disturbances and long-term health risks. However, the underlying mechanism remains largely unknown. We have previously identified Basonuclin1 (BNC1) mutation from a large Chinese POI pedigree and find the targeted Bnc1 mutation mouse exhibites POI. In this study, we find that BNC1 plays a key role in the dynamic balance of ovarian reserve, and maintaining lipid metabolism and redox homeostasis in oocytes during follicular development. Deficiency of BNC1 results in premature follicular activation and accelerated follicular atresia, but doesn’t affect the ovarian primordial follicle reserve. Mechanistically, BNC1 targets the NF2-YAP pathway to trigger oocyte ferroptosis. Inhibition of ferroptosis significantly rescues POI. These findings uncover a novel pathologic mechanism of POI based on BNC1 deficiency and is the first report showing ferroptosis involved in oocyte death.

ORGANISM(S): Mus musculus

PROVIDER: GSE194195 | GEO | 2022/08/31

REPOSITORIES: GEO

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RNA-Seq Facilitates Quantitative Analysis of Wild Type and Bnc1tr/tr ovary Transcriptomes

Project description:Primary ovarian insufficiency (POI) is a clinical syndrome of ovarian dysfunction characterized by premature exhaustion of primordial follicles. POI causes infertility, serious daily life disturbances and long-term health risks. However, the underlying mechanism remains largely unknown. We have previously identified Basonuclin1 (BNC1) mutation from a large Chinese POI pedigree and find the targeted Bnc1 mutation mouse exhibites POI. In this study, we find that BNC1 plays a key role in the dynamic balance of ovarian reserve, and maintaining lipid metabolism and redox homeostasis in oocytes during follicular development. Deficiency of BNC1 results in premature follicular activation and accelerated follicular atresia, but doesn’t affect the ovarian primordial follicle reserve. Mechanistically, BNC1 targets the NF2-YAP pathway to trigger oocyte ferroptosis. Inhibition of ferroptosis significantly rescues POI. These findings uncover a novel pathologic mechanism of POI based on BNC1 deficiency and is the first report showing ferroptosis involved in oocyte death.

2022-08-31 | GSE194196 | GEO

RNA-Seq Facilitates Quantitative Analysis of Wild Type and Bnc1tr/tr oocyte Transcriptomes

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Transcriptome analysis during VCD exposure-induced POI in mice

Project description:4-vinylcyclohexene diepoxide (VCD) is a reproductively toxic environmental pollutant that causes follicular failure leading to POIs, which can seriously affect a woman's physical health and fertility. Investigating its pathogenic mechanisms can help provide guidance for the prevention of ovarian impairment and the treatment of POI. We built a mouse model of POI by intraperitoneal injection of VCD into female C57BL/6 mice for 15 days. Then compared it with the control group at two time points, day 15 and day 30, including the comparison of phenotypic characteristics and differences in the transcriptome. We performed a comprehensive analysis of the differential genes identified and validated some key genes by RT-PCR. The results showed that sex hormone levels, follicle number and estrous cycle of VCD-induced POI mice were significantly affected at both day 15 and day 30. Regarding DEGs and enrichment results, the results obtained at day 15 were not as significant as those at day 30. Our results provide a preliminary indication that steroid hormone synthesis, DNA damage repair, and impaired oocyte mitosis play an important part in the process by which VCD affects ovarian function. Maybe it was due to impaired follicular development caused by VCD damage to the primordial follicular pool, and with the progression of time, the ovarian damage was aggravated, and it was gradually difficult to perform normal function.

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