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Research resource: preovulatory LH surge effects on follicular theca and granulosa transcriptomes.

ABSTRACT: The molecular mechanisms that regulate the pivotal transformation processes observed in the follicular wall following the preovulatory LH surge, are still not established, particularly for cells of the thecal layer. To elucidate thecal cell (TC) and granulosa cell (GC) type-specific biologic functions and signaling pathways, large dominant bovine follicles were collected before and 21 hours after an exogenous GnRH-induced LH surge. Antral GCs (aGCs; aspirated by follicular puncture) and membrane-associated GCs (mGCs; scraped from the follicular wall) were compared with TC expression profiles determined by mRNA microarrays. Of the approximately 11 000 total genes expressed in the periovulatory follicle, only 2% of thecal vs 25% of the granulosa genes changed in response to the LH surge. The majority of the 203 LH-regulated thecal genes were also LH regulated in GCs, leaving a total of 57 genes as LH-regulated TC-specific genes. Of the 57 thecal-specific LH-regulated genes, 74% were down-regulated including CYP17A1 and NR5A1, whereas most other genes are being identified for the first time within theca. Many of the newly identified up-regulated thecal genes (eg, PTX3, RND3, PPP4R4) were also up-regulated in granulosa. Minimal expression differences were observed between aGCs and mGCs; however, transcripts encoding extracellular proteins (NID2) and matrix modulators (ADAMTS1, SASH1) dominated these differences. We also identified large numbers of unknown LH-regulated GC genes and discuss their putative roles in ovarian function. This Research Resource provides an easy-to-access global evaluation of LH regulation in TCs and GCs that implicates numerous molecular pathways heretofore unknown within the follicle.

SUBMITTER: Christenson LK

PROVIDER: S-EPMC3706842 | biostudies-other | 2013 Jul

REPOSITORIES: biostudies-other

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Research resource: preovulatory LH surge effects on follicular theca and granulosa transcriptomes.

Christenson Lane K LK Gunewardena Sumedha S Hong Xiaoman X Spitschak Marion M Baufeld Anja A Vanselow Jens J

Molecular endocrinology (Baltimore, Md.) 20130528 7

The molecular mechanisms that regulate the pivotal transformation processes observed in the follicular wall following the preovulatory LH surge, are still not established, particularly for cells of the thecal layer. To elucidate thecal cell (TC) and granulosa cell (GC) type-specific biologic functions and signaling pathways, large dominant bovine follicles were collected before and 21 hours after an exogenous GnRH-induced LH surge. Antral GCs (aGCs; aspirated by follicular puncture) and membrane ...[more]

PMID: 23716604

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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.

Project description:Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease in women of reproductive age. Ovarian dysfunction including abnormal steroid hormone synthesis and follicular arrest play a vital role in PCOS pathogenesis. Hyperandrogenemia is one of the important characteristics of PCOS. However, the mechanism of regulation and interaction between hyperandrogenism and ovulation abnormalities are not clear. To investigate androgen-related metabolic state in granulosa cells of PCOS patients, we identified the transcriptome characteristics of PCOS granulosa cells by RNA-seq. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes (DEGs) revealed that genes enriched in lipid metabolism pathway, fatty acid biosynthetic process and ovarian steroidogenesis pathway were abnormally expressed in PCOS granulosa cells in comparison with that in control. There are close interactions among these three pathways as identified by analysis of the protein-protein interaction (PPI) network of DEGs. Furthermore, in vitro mouse follicle culture system was established to explore the effect of high androgen and its related metabolic dysfunction on follicular growth and ovulation. RT-qPCR results showed that follicles cultured with dehydroepiandrosterone (DHEA) exhibited decreased expression levels of cumulus expansion-related genes (Has2, Ptx3, Tnfaip6 and Adamts1) and oocyte maturation-related genes (Gdf9 and Bmp15), which may be caused by impaired steroid hormone synthesis and lipid metabolism, thus inhibited follicular development and ovulation. Furthermore, the inhibition effect of DHEA on follicle development and ovulation was ameliorated by flutamide, an androgen receptor (AR) antagonist, suggesting the involvement of AR signaling. In summary, our study offers new insights into understanding the role of androgen excess induced granulosa cell metabolic disorder in ovarian dysfunction of PCOS patients.

Dataset Information

Research resource: preovulatory LH surge effects on follicular theca and granulosa transcriptomes.

Publications

Research resource: preovulatory LH surge effects on follicular theca and granulosa transcriptomes.

Similar Datasets

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