Sustained ERK1/2 signaling is necessary for follicular rupture during ovulation in mice
| Autor: | Philippe P. Roux, Dayananda Siddappa, Vilceu Bordignon, Yasmin Schuermann, Ejimedo Madogwe, Raj Duggavathi |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Ovulation
Gene isoform endocrine system Embryology MAP Kinase Signaling System media_common.quotation_subject Biology Andrology Mice Endocrinology Follicular phase Gene expression medicine Animals Gene media_common Mice Knockout Granulosa Cells Obstetrics and Gynecology Cell Biology medicine.disease Oocyte Luteinization medicine.anatomical_structure Reproductive Medicine Female Extracellular Matrix Degradation Infiltration (medical) |
| Zdroj: | Reproduction. 161:183-193 |
| ISSN: | 1741-7899 1470-1626 |
| Popis: | Abolition of the LH-induced ERK1/2 pathway leads to dramatic changes in gene expression in granulosa cells, subsequently abrogating ovulation. Here we explored whether sustained ERK1/2 signaling beyond immediate-early hours of the LH surge is important for ovulation in mice. First, we examined the effect of inhibition of ERK1/2 activity at 4 h after hCG stimulation on ovulation in superovulated immature mice. Treatment with the ERK1/2 pathway inhibitor PD0325901 at 4 h post-hCG disrupted follicular rupture without altering cumulus expansion, oocyte meiotic maturation and luteinization. Profiling the expression pattern of genes of the RSK family of ERK1/2 signal mediators revealed that RSK3, but not other isoforms, was induced by hCG treatment. Further, RSK3-knockout mice were sub-fertile with reduced ovulation rate and smaller litter size compared to WT mice. Given that PD0325901 inhibits all mediators of ERK1/2 signaling, we chose to evaluate the gene expression underlying deficient follicular rupture in ERK1/2 inhibited mice. We found that inhibition of ERK1/2 signaling at 4 h post-hCG resulted in an imbalance in the expression of genes involved in extracellular matrix degradation and leukocyte infiltration necessary for follicular rupture. In conclusion, our data demonstrate that sustained ERK1/2 signaling during ovulation is not required for cumulus expansion, oocyte meiotic maturation and luteinization, but is required for follicular rupture. |
| Databáze: | OpenAIRE |
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