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Updated: Feb 3, 2026
Gene Expression Analyses in Human Follicles
Published on: February 17, 2023
ERK1/2-dependent gene expression in the bovine ovulating follicle
Yasmin Schuermann1, Monique T Rovani2, Bernardo Gasperin3
1Department of Animal Science, McGill University, Sainte-Anne-de-Bellevue, QC, H9X 3V9, Canada.
Abstract:
Ovulation is triggered by gonadotropin surge-induced signaling cascades. To study the role of extracellular signal-regulated kinase 1/2 (ERK1/2) in bovine ovulation, we administered the pharmacological inhibitor, PD0325901, into the preovulatory dominant follicle by intrafollicular injection. Four of five cows treated with 50 µM PD0325901 failed to ovulate. To uncover the molecular basis of anovulation in ERK1/2-inhibited cows, we collected granulosa and theca cells from Vehicle and PD0325901 treated follicles. Next-generation sequencing of granulosa cell RNA revealed 285 differentially expressed genes between Vehicle and PD0325901-treated granulosa cells at 6 h post-GnRH. Multiple inflammation-related pathways were enriched among the differentially expressed genes. The ERK1/2 dependent LH-induced genes in granulosa cells included EGR1, ADAMTS1, STAT3 and TNFAIP6. Surprisingly, PD0325901 treatment did not affect STAR expression in granulosa cells at 6 h post-GnRH. Granulosa cells had higher STAR protein and theca cells had higher levels of STAR mRNA in ERK1/2-inhibited follicles. Further, both granulosa and theca cells of ERK1/2-inhibited follicles had higher expression of SLC16A1, a monocarboxylate transporter, transporting substances including β-hydroxybutyrate across the plasma membrane. Taken together, ERK1/2 plays a significant role in mediating LH surge-induced gene expression in granulosa and theca cells of the ovulating follicle in cattle.
Insights
Extracellular signal-regulated kinase 1/2 (ERK1/2) is crucial for bovine ovulation, as inhibiting it prevents follicle rupture. This study reveals ERK1/2 mediates key gene expression changes necessary for ovulation.
Area of Science:
- Reproductive Biology
- Molecular Endocrinology
- Cell Signaling
Background:
- Ovulation is a complex process initiated by a surge in gonadotropins.
- Signaling cascades, including those involving extracellular signal-regulated kinase 1/2 (ERK1/2), are critical for ovulation.
- The precise role of ERK1/2 in mediating the luteinizing hormone (LH) surge's effects on the ovulatory follicle remains to be fully elucidated.
Purpose of the Study:
- To investigate the role of ERK1/2 signaling in the process of bovine ovulation.
- To identify molecular pathways and genes regulated by ERK1/2 in response to the LH surge in granulosa and theca cells.
Main Methods:
- Administration of the ERK1/2 inhibitor PD0325901 via intrafollicular injection in preovulatory dominant follicles of cows.
- Collection of granulosa and theca cells at 6 hours post-GnRH administration for molecular analysis.
- Next-generation sequencing (NGS) of granulosa cell RNA to identify differentially expressed genes and enriched pathways.
Main Results:
- Inhibition of ERK1/2 led to anovulation in 4 out of 5 treated cows.
- NGS revealed 285 differentially expressed genes in granulosa cells, with enrichment of inflammation-related pathways.
- Key ERK1/2-dependent LH-induced genes in granulosa cells included EGR1, ADAMTS1, STAT3, and TNFAIP6.
- STAR expression was not affected in granulosa cells at 6h post-GnRH, but STAR protein was higher in granulosa cells and STAR mRNA in theca cells of inhibited follicles.
- Increased expression of the monocarboxylate transporter SLC16A1 was observed in both cell types.
Conclusions:
- ERK1/2 signaling is essential for mediating LH surge-induced gene expression in bovine granulosa and theca cells.
- Disruption of ERK1/2 signaling significantly impairs ovulation, likely through the modulation of inflammation and specific gene expression patterns.
- ERK1/2 plays a critical role in the molecular events leading to follicle rupture in cattle.
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