May 13, 2014
Male Fertility Relies On A Key Protein That Also Protects Against Disease
Brett Smith for redOrbit.com - Your Universe Online
Male infertility prevents many couples from being able to conceive a child and a new study published in the journal Nature Communications has found a specific protein that is a major determining factor in determining a sperm’s ability to fertilize an egg.
The protein, known as Chd5, is responsible for effectively packaging DNA inside the head of a sperm, where space it at a premium.
Each cell in the body contains an entire copy of a person’s genome – which would extend to about 6 feet if completely unraveled into a single strand. To pack this enormous span of DNA, cells snugly compress our DNA into every cell nucleus. The DNA is packed like thread wrapped around protein spools, known as histones. The system allows for thread to be easily unwound at any moment to permit accessibility to the DNA.
In a sperm cell, which contains half of a genome, genetic material must be even more condensed. To conserve some space, histones are substituted with small proteins called protamines. This is done through a repackaging process called chromatin remodeling. Only about 50 micrometers long, a sperm must be effectively constructed to search for an egg and deliver its genetic payload.
In the new study, researchers found the Chd5 is a major regulator of chromatin remodeling during sperm maturity. Study author Alea Mills, a professor at Cold Spring Harbor Laboratory, said she first became interested in Chd5 after her research team found it to be a strong tumor suppressor in 2007.
"We know this ability has something to do with chromatin remodeling – that when defective, causes normal cells to transform into tumors," Mills said. "But the most dramatic chromatin reorganization occurs when specialized cells carrying our genetic blueprint develop into sperm cells. It makes sense that Chd5 would be functioning there, too."
The study team found that when they took out both copies of the Chd5 gene from lab mice, the rodents had significant fertility defects, including low sperm counts and reduced sperm motility. The faulty sperm could not fertilize eggs when in vitro fertilization (IVF) was executed in the lab.
Looking closer, the team discovered that histones were not efficiently substituted with protamines in the mice without Chd5, resulting in a more irregular, less compact genome. This haphazard packaging resulted in the DNA double helix becoming damaged and breaking at several points throughout.
"So in addition to infertility, loss of Chd5 may put future generations – the rare embryos that do get fertilized with defective sperm – at risk for disease," Mills said. "Chd5 may protect a person from medical conditions related to DNA damage and spontaneous mutations, like cancer and autism."
The researchers said their current work is looking at the role of Chd5 in human fertility through the analysis of Chd5 levels using testes biopsies taken from men with fertility defects.
"We found that men with more severe defects had the lowest levels of Chd5," Mills said. "While it is only a correlation at this point, we are eager to understand fully how Chd5 affects sperm development in humans."