Journal article
Roles of Gremlin 1 and Gremlin 2 in regulating ovarian primordial to primary follicle transition
Reproduction (Cambridge, England), Vol.147(6), pp.865-874
06/2014
PMCID: PMC4043579
PMID: 24614542
Abstract
A network of extracellular signaling factors has previously been shown to act in concert to control the ovarian primordial to primary follicle transition. The current study was designed to investigate the roles of the endogenous bone morphogenetic protein (BMP) inhibitors Gremlin 1 (GREM1) and GREM2 in primordial follicle transition in the rat ovary. GREM1 and GREM2 treatments were found to reverse the effects of anti-Müllerian hormone (AMH) to inhibit follicle transition in a whole-ovary culture system. GREM1 reversed the effect of BMP4 to stimulate primordial follicle transition. Immunohistochemical studies showed that GREM2, but not GREM1, was present in primordial follicles suggesting that GREM2 may regulate primordial follicle transition in vivo. Co-immunoprecipitation studies indicated that GREM2 directly binds to AMH, as well as to BMP4. Transcriptome analyses of ovaries treated with GREM2 or GREM1 yielded negligible numbers of differentially expressed genes, suggesting that the immediate effects of GREM2 or GREM1 appear to be at the level of protein-protein interactions, rather than direct actions on the cells. A number of other ovarian growth factors were found to influence the expression of Grem2. Observations suggest that Grem2 is a part of the signaling network of growth factors that regulate the primordial to primary follicle transition. Insights into the regulatory networks affecting the pool of primordial follicles are important to understand the molecular basis for reproductive diseases such as primary ovarian insufficiency.
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Details
- Title
- Roles of Gremlin 1 and Gremlin 2 in regulating ovarian primordial to primary follicle transition
- Creators
- Eric E Nilsson - Washington State UniversityGinger Larsen - School of Biological SciencesCenter for Reproductive Biology, Washington State University, Pullman, Washington 99164-4236, USAMichael K Skinner - School of Biological SciencesCenter for Reproductive Biology, Washington State University, Pullman, Washington 99164-4236, USA skinner@wsu.edu
- Publication Details
- Reproduction (Cambridge, England), Vol.147(6), pp.865-874
- Academic Unit
- Biological Sciences, School of
- Grant note
- R01 ES012974 / NIEHS NIH HHS R01 HD048898 / NICHD NIH HHS
- Identifiers
- 99901080309601842
- Language
- English
- Resource Type
- Journal article