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Changes in ovarian granulosa cell chromatin interactions in response to LH surge

ABSTRACT: Luteinising hormone (LH) surge leads to widespread genomic changes in ovarian granulosa cells, leading to global regulation of genes that are important for ovulation and female reproduction. While LH-dependent changes in chromatin accessibility, histone modification and transcription factor activation have been previously described, the influence of the LH-surge on three-dimensional chromatin organisation as well as the activation of enhancer regulatory elements remain unknown. This study aims to characterise the chromatin 3D structure in granulosa cells, from which to determine changes in chromatin-chromatin interactions and enhancer activation in response to the LH-surge.

ORGANISM(S): Mus musculus

PROVIDER: GSE300455 | GEO | 2026/08/07

REPOSITORIES: GEO

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Project description:The molecular mechanisms that regulate the pivotal transformation processes observed in the follicular wall following the pre-ovulatory LH-surge, are still not established, particularly for cells of the thecal layer. To elucidate thecal and granulosa cell type-specific biological functions and signaling pathways, large dominant bovine follicles were collected before and 21 hrs after an exogenous GnRH induced LH surge. Because LH receptor density varies within the granulosa cell populations, antral granulosa (aGC; those aspirated by follicular puncture) and membrane associated granulosa (mGC; those scraped from the follicular wall) were compared to thecal cell expression profiles determined by mRNA microarrays. Thecal cell gene expression was less affected in the peri-ovulatory follicle when compared to granulosa cells, as evidenced by only 2% versus 25% of the ~11,000 genes expressed changing in response to the LH surge, respectively. The majority of the 203 LH-regulated thecal genes were also LH regulated in granulosa cells, leaving a total of 58 genes as LH-regulated theca cell specific genes. Most of the 58 genes (i.e., 74%) thecal specific genes including several known thecal markers (CYP17A1, NR5A1) were downregulated, while most genes identified are new to theca. Many of the newly identified upregulated thecal genes (e.g., PTX3, RND3, PPP4R4) were also upregulated in granulosa. Minimal expression differences were observed between aGC and mGC, however, transcripts encoding extracellular proteins (NID2) and matrix modulators (ADAMTS1, SASH1) predominated these differences. We also identified large numbers of unknown LH-regulated granulosa cell genes and discuss their putative roles in ovarian function. The single dominant ovarian follicle was collected from each cow before the LH surge or 22 hours after GnRH (used to induce LH surge). RNA was extracted from three independent cells within each follicle and there were hybridized on Affymetrix microarrays.

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Changes in ovarian granulosa cell chromatin interactions in response to LH surge

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