Hidden DNA safeguard explains infertility, miscarriages and Down syndrome

Scientists at UC Davis discover how protein networks protect chromosomes for decades, reducing risks of infertility, miscarriage and genetic disorders

A hidden DNA safeguard that protects chromosomes during the formation of eggs and sperm has been discovered, offering fresh insight into why infertility, miscarriages, and genetic disorders like Down syndrome occur. 

The finding, reported in Nature in the study titled Protecting double Holliday junctions ensures crossing over during meiosis by researchers at the University of California, Davis, shows how protein networks preserve chromosome crossovers and maintain genetic stability across generations.

 

What is this hidden DNA process all about?

 

At the heart of the discovery lies a structure called the double Holliday junction, which is a tiny DNA bridge that keeps chromosomes connected as eggs and sperm form. These connections, called “crossovers,” are vital for ensuring that each egg or sperm gets the right set of chromosomes. Without them, errors creep in, leading to extra or missing chromosomes, a major cause of miscarriage, infertility, and conditions such as Down syndrome. 

 

 

Why does it matter for women’s fertility?

 

According to the study, in women, eggs form while they are still in their mother’s womb. These immature eggs stay frozen in time for decades before ovulation. For all those years, their chromosomes must remain properly connected. If the DNA crossovers are not protected, the chromosomes can drift apart, causing mistakes during cell division later in life. This explains why risks of miscarriage and genetic disorders increase with maternal age.

 

What did the study reveal?

 

The UC Davis team used yeast as a model organism to watch this unfold in real time, as the proteins involved are nearly identical to those in humans. Using a technique called real-time genetics, the researchers could switch specific proteins on and off, observing how crossovers form, or fail.

 

The study revealed that certain protein complexes, including cohesin and synaptonemal complex proteins, act as guardians. They shield the double Holliday junctions from being dismantled too early by some enzymes. “They protect the double Holliday junction — that is a key discovery,” Neil Hunter, a professor in the Department of Microbiology and Molecular Genetics, said in a statement on the website of UC Davis. In simple terms, without these guardians, the genetic handoff between generations could collapse. 

 

How does this link to miscarriages and Down syndrome?

 

If chromosomes do not separate correctly, the resulting eggs or sperm may have the wrong number of chromosomes. In humans, this often leads to failed pregnancies or disorders like Down syndrome, which arises from an extra copy of chromosome 21. As the UC Davis statement put it, this discovery reveals a critical event that guides the accurate distribution of chromosomes to eggs and sperm, with direct consequences for reproductive health.

 

What does this mean for fertility treatments?

 

According to the researchers, understanding how eggs and sperm maintain chromosome stability opens doors to new diagnostics and fertility interventions. This will support doctors to one day be able to identify when these protective mechanisms fail, and intervene earlier to reduce the risk of miscarriage or improve IVF outcomes.