Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 434, Issue C, Pages 116-126Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2016.06.020
Keywords
FOXO1; Granulosa cells; Follicle-stimulating hormone; RNA deep sequencing
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Funding
- National Institutes of Health [R01HD065859, R01HD62503, T32GM083864]
- Poncin Fellowship Fund
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FSH promotes maturation of ovarian follicles. One pathway activated by FSH in granulosa cells (GCs) is phosphatidylinositol-3 kinase/AKT. The ART target FOXO1 is reported to function primarily as a repressor of FSH genes, including Ccnd2 and Inha. Based on its broad functions in other tissues, we hypothesized that FOXO1 may regulate many more GC genes. We transduced GCs with empty adenovirus or constitutively active FOXO1 followed by treatment with FSH for 24 h, and conducted RNA deep sequencing. Results show that FSH regulates 3772 genes >= 2.0-fold; 60% of these genes are activated or repressed by FOXO1. Pathway Studio Analysis revealed enrichment of genes repressed by FOXO1 in metabolism, signaling, transport, development, and activated by FOX01 in signaling, cytoskeletal functions, and apoptosis. Gene regulation was verified by q-PCR (eight genes) and ChIP analysis (two genes). We conclude that FOXO1 regulates the majority of FSH target genes in GCs. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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