Centromeres and early embryo development
When a sperm fertilizes an egg, the resulting zygote must quickly reassemble a unified genome from two parental sets of chromosomes. A key part of this process is the centromere, a chromosome region that acts like a handle for pulling the DNA apart during cell division. For decades, scientists believed that centromeres from sperm and egg were essentially the same in function because the critical histone protein CENPA marks these regions and is typically preserved across cell divisions and generations.
New research from the University of Michigan challenges that assumption. In the lab of Sue Hammoud, Ph.D., scientists found that sperm contribute far less CENPA to centromere DNA than the egg does. If this imbalance were left uncorrected, it could compromise chromosome segregation and raise the risk of aneuploidies—chromosome-number abnormalities linked to miscarriage and developmental disorders like Down syndrome.
The puzzle of CENPA and centromere identity
The prevailing view was that centromeric identity is maintained by CENPA, a unique histone tag that should keep centromeres functionally identical across parental genomes and cell generations. The Michigan team’s observations showed this is not the full story. The paternal centromeres begin life with a comparatively thin CENPA setup, creating a potential mismatch as the embryo prepares for its first cell division. The natural question then became: how do embryos overcome this discrepancy to ensure faithful division?
How maternal and paternal centromeres balance
To answer this, researchers tracked maternal and paternal CENPA within mouse embryos produced by in vitro fertilization. The surprise came from a second player: CENPC, a centromere-associated protein that acted as a recruiter. CENPC preferentially accumulated on the father’s chromosomes, drawing additional CENPA from the egg’s cytoplasm toward paternal centromeres until the levels matched those on maternal centromeres. In other words, embryonic centromere strength is equalized just before the first division, ensuring proper chromosome segregation.
The role of CENPC and the recruitment mechanism
The study shows that CENPC is not merely a structural component; it serves as a regulator that recruits egg-derived CENPA to paternal centromeres. This dynamic balancing act appears to be a universal feature, observed not only in mice but also in humans, according to the team. The process may explain why some zygotes proceed smoothly through early divisions while others stall, tied to variability in how much CENPA each egg can supply and how effectively CENPC can mobilize it.
Implications for human fertility and therapies
Variability in CENPA levels across individual eggs could contribute to differences in embryo viability. Those eggs with relatively low CENPA may be more prone to centromere imbalance, potentially leading to developmental delays or arrested embryos. This insight opens doors to new therapeutic avenues—if scientists can modulate centromere components or enhance CENPA recruitment in eggs, it might improve embryo quality for some individuals undergoing assisted reproduction.
What this means for IVF and miscarriage risk
Aneuploidies are a leading cause of miscarriage and developmental disorders. By revealing a cellular mechanism that helps equalize centromeres before the first cell division, the research adds a potential explanation for embryo failures and a possible target for reducing such outcomes. The findings emphasize the importance of centromere biology in early development and offer a platform for exploring interventions in cases where egg quality or centromere balance is suboptimal.
Future directions
Going forward, scientists aim to confirm these findings in human embryos and to understand how maternal and paternal factors interact with a broader network of centromere-associated proteins. If the balance of CENPA and CENPC proves to be a controllable lever, it could lead to diagnostic tools or therapies that improve embryo viability in IVF and reduce miscarriage rates.
