News | Hidden DNA secrets: scientists uncover molecular roots of infertility and miscarriage
The stability of human reproduction is shaped before birth by a molecular "dance." Researchers at the University of California, Davis have revealed how a key mechanism deep within DNA protects chromosome integrity as eggs and sperm form. The finding offers a new scientific perspective on infertility, miscarriage and reproductive conditions such as Down syndrome, and may support future fertility treatments.
The research, led by Neil Hunter, professor in the Department of Microbiology and Molecular Genetics, was published in Nature on September 24. For the first time, it maps in detail how chromosomes remain connected through crossovers during egg and sperm development, preventing errors in genetic distribution.
A chromosome "safety lock" for accurate transmission of genetic information
Professor Hunter explained: "If this process goes wrong, eggs or sperm may carry the wrong number of chromosomes, ultimately leading to infertility, miscarriage or genetic conditions such as Down syndrome."
Human cells contain 46 chromosomes arranged in 23 homologous pairs. As eggs or sperm form, the paired chromosomes must align and undergo breakage and recombination at specific sites to create crossovers. This gives each child a unique combination of genes from both parents while keeping chromosome pairs stable.
Maintaining these connections is especially complex in women. Egg cells form during fetal development and become dormant after crossovers are completed, resuming activity only at ovulation decades later. How crossover connections remain stable for so long has been an unresolved question in reproductive biology.
Yeast reveals clues to human biology
To investigate, Hunter's team used yeast, a widely used model in molecular genetics, to track chromosome recombination at the molecular level. With "real-time genetics," researchers induced selected proteins to degrade under controlled conditions and observed whether crossover structures formed correctly.
The results showed that a network of key proteins, particularly the cohesin complex, prevents the STR complex—called the Bloom complex in humans—from prematurely unwinding DNA crossover structures. This protection is essential for stabilizing the double Holliday junction.
"These proteins act like guards protecting chromosome connections from being dismantled incorrectly," Hunter said. "This is a crucial step in preventing chromosome segregation errors."
From basic research to fertility medicine
Although the study used yeast, Hunter emphasized that the relevant chromosome structures and mechanisms are highly conserved in humans. This basic research may therefore directly inform understanding of human reproductive disorders and improvements in fertility diagnosis and treatment.
The study was co-led by postdoctoral researcher Shangming Tang, now an assistant professor of biochemistry and molecular genetics at the University of Virginia, and funded by the National Institutes of Health (NIH), Howard Hughes Medical Institute (HHMI), UC Davis Comprehensive Cancer Center and American Cancer Society.
News | Hidden Secrets in DNA: Scientists Uncover the Molecular Roots of Infertility and Miscarriage
News | Hidden DNA secrets: scientists uncover molecular roots of infertility and miscarriage
The stability of human reproduction is shaped before birth by a molecular "dance." Researchers at the University of California, Davis have revealed how a key mechanism deep within DNA protects chromosome integrity as eggs and sperm form. The finding offers a new scientific perspective on infertility, miscarriage and reproductive conditions such as Down syndrome, and may support future fertility treatments.
The research, led by Neil Hunter, professor in the Department of Microbiology and Molecular Genetics, was published in Nature on September 24. For the first time, it maps in detail how chromosomes remain connected through crossovers during egg and sperm development, preventing errors in genetic distribution.
A chromosome "safety lock" for accurate transmission of genetic information
Professor Hunter explained: "If this process goes wrong, eggs or sperm may carry the wrong number of chromosomes, ultimately leading to infertility, miscarriage or genetic conditions such as Down syndrome."
Human cells contain 46 chromosomes arranged in 23 homologous pairs. As eggs or sperm form, the paired chromosomes must align and undergo breakage and recombination at specific sites to create crossovers. This gives each child a unique combination of genes from both parents while keeping chromosome pairs stable.
Maintaining these connections is especially complex in women. Egg cells form during fetal development and become dormant after crossovers are completed, resuming activity only at ovulation decades later. How crossover connections remain stable for so long has been an unresolved question in reproductive biology.
Yeast reveals clues to human biology
To investigate, Hunter's team used yeast, a widely used model in molecular genetics, to track chromosome recombination at the molecular level. With "real-time genetics," researchers induced selected proteins to degrade under controlled conditions and observed whether crossover structures formed correctly.
The results showed that a network of key proteins, particularly the cohesin complex, prevents the STR complex—called the Bloom complex in humans—from prematurely unwinding DNA crossover structures. This protection is essential for stabilizing the double Holliday junction.
"These proteins act like guards protecting chromosome connections from being dismantled incorrectly," Hunter said. "This is a crucial step in preventing chromosome segregation errors."
From basic research to fertility medicine
Although the study used yeast, Hunter emphasized that the relevant chromosome structures and mechanisms are highly conserved in humans. This basic research may therefore directly inform understanding of human reproductive disorders and improvements in fertility diagnosis and treatment.
The study was co-led by postdoctoral researcher Shangming Tang, now an assistant professor of biochemistry and molecular genetics at the University of Virginia, and funded by the National Institutes of Health (NIH), Howard Hughes Medical Institute (HHMI), UC Davis Comprehensive Cancer Center and American Cancer Society.
Story source:
Collected online