March 19, 2019
RIKEN
Keio University School of Medicine
A research team led by Dr. Toru Matsuura, a researcher at the RIKEN Center for Brain Science, Laboratory for Developmental Neurobiology (currently a lecturer at the Department of Experimental Pathology, Kansai Medical University School of Medicine), and Dr. Katsuhiko Mikoshiba, Team Leader at the same laboratory and Guest Professor at the Department of Pharmacology, Keio University School of Medicine, has discovered a new mechanism in mouse fertilization. They found that calcium ions released within the fertilized egg trigger further calcium ion release through a positive feedback loop, thereby maintaining oscillations in calcium ion concentration (calcium oscillations) for several hours.
In most mammalian species, including humans, ovulated eggs are arrested at the metaphase of the second meiotic division. They are activated upon fertilization by a sperm, initiating development. This egg activation is triggered by calcium oscillations.
Fertilization causes the calcium ion concentration inside the egg to repeatedly rise and fall. This process triggers egg activation events such as cortical granule exocytosis, inactivation of the cytostatic factor, second polar body extrusion, and pronuclear formation. These calcium oscillations are sustained for several hours. It is known that there is a relationship between the duration of calcium oscillations and embryonic development, making the maintenance of these oscillations crucial for normal embryonic development.
The research team first developed a new, genetically encodable sensor to visualize inositol 1,4,5-trisphosphate (IP 3 ), a substance that increases intracellular calcium ion concentration, and calcium ions themselves.
This new IP 3 sensor is 10 times more sensitive than previous ones, enabling the world's first successful detection of minute changes in IP 3 concentration within a fertilized egg. The team also developed a calcium sensor that can be used in conjunction with this IP 3 sensor.
Using these sensors, the research team measured changes in IP 3 and calcium ion concentrations within fertilized eggs. They revealed that an increase in calcium ion concentration activates the phospholipase C (PLC) enzyme, which in turn produces more IP 3 . In other words, this positive feedback loop involving calcium, PLC, and IP 3 leads to the accumulation of IP 3 within the egg after fertilization, which sustains long-lasting calcium oscillations and promotes normal embryonic development.
This research was published in the online edition of the British scientific journal "Scientific Reports" on Monday, March 18, 2019 (UK time).
For the full press release, please see below.