NIH Research Festival
In mammals, a new life is initiated by repetitive changes in the egg‚Äôs intracellular calcium (Ca2+) level, or Ca2+ oscillations. Ca2+ oscillations are environmentally responsive and can be altered in vitro by changing the composition of culture media, such as in assisted reproduction, or in vivo by medical conditions, such as obesity or inflammation. In mice, slightly increased Ca2+ exposure negatively impacts offspring growth and health. We wondered ‚ÄúHow much Ca2+ is too much Ca2+‚Äù? To answer this question I developed a mouse model with extreme Ca2+ conditions during fertilization by targeting the two main plasma membrane Ca2+ pumps (PMCA) in mouse oocytes. PMCAs extrude Ca2+ from the cytosol following Ca2+ release events, so I hypothesized that deleting PMCAs in oocytes would result in prolonged Ca2+ exposure at fertilization, leading to altered fertility and embryo development. As expected, PMCA1/PMCA3-null eggs (dKO) had a dramatically extended Ca2+ exposure at fertilization (10 times more). Females carrying dKO eggs had fewer pups per litter than controls. To understand when fertility defects occur as a result of increased Ca2+, dKO and control eggs were fertilized in vitro and monitored for development. Most of the fertilized dKO eggs arrested their development at early cleavage stages (2-cell to 4-cell stages). Similarly, embryo development was impaired in dKO eggs fertilized in vivo (mating) and cultured in vitro. Our results suggest that 10 times more Ca2+ is ‚Äútoo much‚Äù Ca2+ for embryo development and raise awareness of the importance of appropriate Ca2+ exposure at fertilization.
Scientific Focus Area: Developmental Biology
This page was last updated on Monday, September 25, 2023