| First Author | Binder AK | Year | 2013 |
| Journal | Endocrinology | Volume | 154 |
| Issue | 6 | Pages | 2174-87 |
| PubMed ID | 23580569 | Mgi Jnum | J:198474 |
| Mgi Id | MGI:5496777 | Doi | 10.1210/en.2012-2256 |
| Citation | Binder AK, et al. (2013) The absence of ER-beta results in altered gene expression in ovarian granulosa cells isolated from in vivo preovulatory follicles. Endocrinology 154(6):2174-87 |
| abstractText | Determining the spatial and temporal expression of genes involved in the ovulatory pathway is critical for the understanding of the role of each estrogen receptor in the modulation of folliculogenesis and ovulation. Estrogen receptor (ER)-beta is highly expressed in ovarian granulosa cells, and mice lacking ER-beta are subfertile due to inefficient ovulation. Previous work has focused on isolated granulosa cells or cultured follicles and, although informative, provides confounding results due to the heterogeneous cell types present including granulosa and theca cells and oocytes and exposure to in vitro conditions. Herein we isolated preovulatory granulosa cells from wild-type (WT) and ERbeta-null mice using laser capture microdissection to examine the genomic transcriptional response downstream of pregnant mare serum gonadotropin (mimicking FSH) and pregnant mare serum gonadotropin/human chorionic gonadotropin (mimicking LH) stimulation. This allows for a direct comparison of in vivo granulosa cells at the same stage of development from both WT and ERbeta-null ovaries. ERbeta-null granulosa cells showed altered expression of genes known to be regulated by FSH (Akap12 and Runx2) as well as not previously reported (Arnt2 and Pou5f1) in WT granulosa cells. Our analysis also identified 304 genes not previously associated with ERbeta in granulosa cells. LH-responsive genes including Abcb1b and Fam110c show reduced expression in ERbeta-null granulosa cells; however, novel genes including Rassf2 and Megf10 were also identified as being downstream of LH signaling in granulosa cells. Collectively, our data suggest that granulosa cells from ERbeta-null ovaries may not be appropriately differentiated and are unable to respond properly to gonadotropin stimulation. |
