Epidermal growth factor receptor kinase activity is required for gap junction closure and for part of the decrease in ovarian follicle cGMP in response to LH
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Updated: Jun 9, 2026

A Functional Assay for Gap Junctional Examination; Electroporation of Adherent Cells on Indium-Tin Oxide
Published on: October 18, 2014
Rachael P Norris1, Marina Freudzon, Viacheslav O Nikolaev
1Department of Cell Biology, University of Connecticut Health Center, Farmington, Connecticut 06032, USA.
Abstract:
The meiotic cell cycle in mouse oocytes is arrested in prophase, and then restarted when LH acts on the surrounding granulosa cells. The granulosa cells keep meiosis arrested by providing a source of cGMP that diffuses into the oocyte through gap junctions, and LH restarts the cell cycle by closing the junctions and by decreasing granulosa cell cGMP, thus lowering oocyte cGMP. Epidermal growth factor receptor (EGFR) activation is an essential step in triggering LH-induced meiotic resumption, but its relationship to the cGMP decrease in the follicle is incompletely understood, and its possible function in causing gap junction closure has not been investigated. Here, we use EGFR agonists (epiregulin and amphiregulin) and an EGFR kinase inhibitor (AG1478) to study the function of the EGFR in the signaling pathways leading to the release of oocytes from prophase arrest. Our results indicate that the EGFR kinase contributes to LH-induced meiotic resumption in two different ways. First, it is required for gap junction closure. Second, it is required for an essential component of the decrease in follicle cGMP. Our data show that the EGFR kinase-dependent component of the cGMP decrease is required for LH-induced meiotic resumption, but they also indicate that an as yet unidentified pathway accounts for a large part of the cGMP decrease.
Insights
Luteinizing hormone (LH) restarts mouse oocyte meiosis by closing gap junctions and decreasing cyclic guanosine monophosphate (cGMP). Epidermal growth factor receptor (EGFR) kinase is crucial for these LH-induced events, including gap junction closure and cGMP reduction.
Area of Science:
- Cell Biology
- Reproductive Biology
- Molecular Endocrinology
Background:
- Meiotic cell cycle in mouse oocytes is arrested in prophase.
- Luteinizing hormone (LH) triggers meiotic resumption.
- Granulosa cells maintain meiotic arrest via cyclic guanosine monophosphate (cGMP) and gap junctions.
Purpose of the Study:
- Investigate the role of Epidermal Growth Factor Receptor (EGFR) in LH-induced meiotic resumption.
- Elucidate the relationship between EGFR activation and cGMP decrease in the follicle.
- Determine EGFR's function in gap junction closure during meiotic resumption.
Main Methods:
- Utilized EGFR agonists (epiregulin, amphiregulin) and an EGFR kinase inhibitor (AG1478).
- Studied signaling pathways regulating oocyte meiotic arrest release.
- Assessed the impact of EGFR modulation on gap junction status and follicle cGMP levels.
Main Results:
- EGFR kinase is essential for LH-induced gap junction closure in granulosa cells.
- EGFR kinase activity is required for a significant component of the LH-induced follicle cGMP decrease.
- EGFR kinase-dependent cGMP reduction is necessary for meiotic resumption, but an unknown pathway also contributes to cGMP reduction.
Conclusions:
- EGFR kinase plays a dual role in facilitating LH-induced meiotic resumption.
- EGFR kinase mediates gap junction closure and a portion of the cGMP decrease.
- Further research is needed to identify the complete pathway responsible for cGMP reduction during meiotic resumption.
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