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Updated: Apr 7, 2026
In Vivo Visualization of Calcium Transients during Fertilization and Early Development in C. elegans
Published on: July 12, 2024
Regulator of G-protein signaling 2 (RGS2) suppresses premature calcium release in mouse eggs
Miranda L Bernhardt1, Katie M Lowther2, Elizabeth Padilla-Banks1
1Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Abstract:
During oocyte maturation, capacity and sensitivity of Ca(2+) signaling machinery increases dramatically, preparing the metaphase II (MII)-arrested egg for fertilization. Upon sperm-egg fusion, Ca(2+) release from IP3-sensitive endoplasmic reticulum stores results in cytoplasmic Ca(2+) oscillations that drive egg activation and initiate early embryo development. Premature Ca(2+) release can cause parthenogenetic activation prior to fertilization; thus, preventing inappropriate Ca(2+) signaling is crucial for ensuring robust MII arrest. Here, we show that regulator of G-protein signaling 2 (RGS2) suppresses Ca(2+) release in MII eggs. Rgs2 mRNA was recruited for translation during oocyte maturation, resulting in ∼ 20-fold more RGS2 protein in MII eggs than in fully grown immature oocytes. Rgs2-siRNA-injected oocytes matured to MII; however, they had increased sensitivity to low pH and acetylcholine (ACh), which caused inappropriate Ca(2+) release and premature egg activation. When matured in vitro, RGS2-depleted eggs underwent spontaneous Ca(2+) increases that were sufficient to cause premature zona pellucida conversion. Rgs2(-/-) females had reduced litter sizes, and their eggs had increased sensitivity to low pH and ACh. Rgs2(-/-) eggs also underwent premature zona pellucida conversion in vivo. These findings indicate that RGS2 functions as a brake to suppress premature Ca(2+) release in eggs that are poised on the brink of development.
Insights
Regulator of G-protein signaling 2 (RGS2) prevents premature calcium release in eggs. RGS2 depletion causes spontaneous calcium increases and early egg activation, impacting fertility.
Area of Science:
- Reproductive Biology
- Cell Signaling
- Developmental Biology
Background:
- Oocyte maturation involves increased calcium (Ca2+) signaling capacity, preparing eggs for fertilization.
- Sperm-induced Ca2+ oscillations activate the egg and initiate embryo development.
- Maintaining metaphase II (MII) arrest requires suppression of premature Ca2+ release to prevent parthenogenetic activation.
Purpose of the Study:
- To investigate the role of Regulator of G-protein signaling 2 (RGS2) in suppressing Ca2+ release during oocyte maturation and MII arrest.
- To determine the functional consequences of RGS2 depletion on egg activation and fertility.
Main Methods:
- Quantification of RGS2 protein levels during oocyte maturation.
- In vitro maturation of oocytes with RGS2 depletion using siRNA.
- Assessment of Ca2+ signaling responses to low pH and acetylcholine (ACh) in RGS2-depleted oocytes.
- Evaluation of fertility and egg activation in Rgs2 knockout (Rgs2-/-) mice.
Main Results:
- RGS2 protein levels increase significantly during oocyte maturation.
- RGS2 depletion leads to heightened sensitivity to low pH and ACh, causing inappropriate Ca2+ release and premature egg activation.
- RGS2-depleted eggs exhibit spontaneous Ca2+ increases and premature zona pellucida conversion in vitro.
- Rgs2-/- females show reduced litter sizes, and their eggs display increased sensitivity to stimuli and premature zona pellucida conversion in vivo.
Conclusions:
- RGS2 acts as a critical brake to suppress premature Ca2+ release in MII-arrested eggs.
- RGS2 is essential for maintaining egg arrest and preventing inappropriate activation before fertilization.
- Dysregulation of RGS2 function can lead to infertility due to compromised egg quality and activation timing.
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