缅北强奸

PhD Oral Defence of Ejimedo Madogwe, Animal Science

Infertility affects 1 in 6 couples in Canada. Infertility also affects animal production systems resulting in reduced efficiency and profitability. Fertility is a result of efficient ovarian follicular growth and successful ovulation, which are regulated by the pituitary gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Gonadotropins regulate ovarian functions through signaling pathways such as extracellular signal regulated kinases (ERK1/2) pathway and unique gene expression programs. Histone modifications such as trimethylation of lysine 4 of histone H3 (H3K4me3), a histone mark associated with active transcription, are involved in gene expression. We hypothesized that FSH and LH regulate follicular development and ovulation by instigating specific gene expression programs through the ERK1/2 pathway and H3K4me3. We used mouse models to test this hypothesis. Using RNASequencing, we explored the FSH and LH regulated transcriptome of granulosa cells. We used chromatin immunoprecipitation and sequencing (ChIP-Seq) to identify H3K4me3 enrichment in the promoter of FSH and LH regulated genes. Combination of these techniques with pharmacological inhibition of ERK1/2 signaling revealed ERK1/2 dependent genes in granulosa cells and that ERK1/2 signaling plays a role in H3K4me3 deposition in the promoters of LH-regulated ovulatory genes. Finally, we discovered that sustained ERK1/2 signaling uniquely regulates follicular rupture, without affecting other processes of ovulation such as oocyte meiotic resumption and luteinization. Overall, these studies provide molecular evidence that FSH and LH regulate ovarian follicular development and ovulation through histone modification in ovarian granulosa cells.

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