Sustained ERK1/2 signaling is necessary for follicular rupture during ovulation in mice

Area of Science:

• Reproductive Biology
• Cell Signaling
• Molecular Endocrinology

Background:

• The luteinizing hormone (LH)-induced ERK1/2 pathway is known to affect gene expression in granulosa cells, impacting ovulation.
• The precise role of sustained ERK1/2 signaling beyond the initial hours of the LH surge in the ovulation process remains unclear.

Purpose of the Study:

• To investigate the importance of sustained ERK1/2 signaling for ovulation in mice.
• To determine if ERK1/2 activity is required for specific ovulatory events like follicular rupture, cumulus expansion, oocyte maturation, and luteinization.

Main Methods:

• Inhibition of ERK1/2 activity using PD0325901 at 4 hours post-hCG stimulation in superovulated immature mice.
• Analysis of ovulation rates, cumulus expansion, oocyte meiotic maturation, and luteinization.
• Profiling of RSK family gene expression and evaluation of RSK3-knockout mice.
• Assessment of gene expression related to extracellular matrix degradation and leukocyte infiltration.

Main Results:

• Inhibition of ERK1/2 signaling at 4 h post-hCG disrupted follicular rupture but did not affect cumulus expansion, oocyte meiotic maturation, or luteinization.
• RSK3 was identified as an hCG-induced mediator of the ERK1/2 pathway, and RSK3-knockout mice exhibited sub-fertility with reduced ovulation rates.
• ERK1/2 inhibition led to an imbalance in genes essential for extracellular matrix degradation and leukocyte infiltration, processes critical for follicular rupture.

Conclusions:

• Sustained ERK1/2 signaling is not essential for cumulus expansion, oocyte meiotic maturation, or luteinization.
• Sustained ERK1/2 signaling is critical for achieving follicular rupture during ovulation.
• The ERK1/2 pathway regulates key genes involved in tissue remodeling and immune cell recruitment necessary for ovulation.