University of Oregon biologists have dredged up a pathway through which a certain breast cancer gene affects fertility as well. While BRCA1 gene mutations raise a person’s risk of developing breast cancer, many BRCA1 patients experience fertility issues, which can be aggravated by cancer treatments. New study reveals that this gene is involved in a special cell division process that results in the formation of eggs and sperm cells.
In the case where BRCA1 is mutated and thus cannot fulfil this function, both developing eggs and sperm have multiple genetic errors that cause infertility. ‘This is one discovery that opens one potential therapy of looking at how to fix or treat fertility problems in patients with BRCA1,’ said Libuda, an associate professor at Institute of Molecular Biology at the UO. People assumed that ‘BRCA1’ is implicated, but the way it is implicated was most often not clear.
In a paper published in September this year in the eLife journal, Libuda and her team do the same. The work was done by Erik Toraason who was a graduate student in Libuda’s lab and Alina Salagean, a researcher in the undergraduate category.
Libuda’s laboratory investigates the molecular basis of DNA repair during meiosis, the formation of egg and sperm cells. Mistakes that occur during this process affect the genes of crucially reproductive cells, or are inherited through generations or lead to cases of infertility.
BRCA1 is involved with the quality control during ovary differentiation and DNA repair during oogenesis, that is if DNA repairs are to occur correctly, the team has established. It suppresses an undesirable function of DNA repair that pumps hundreds of mutations into cells by mini-shifts of DNA portions.
“These particular sorts of scar from the microdeletions are connected with another process that is very genotoxic,” Libuda said. It is believed to normally be repressed simply for making these microdeletions, which are undesirable. We determined that BRCA1 is essentially for verifying that this process is not being utilised.
A man’s lifetime Christmas stocking full of sperm is laid down before he is born, so that’s when male fertility issues such as low number of sperm-producing cells, or a low count, begin as well. “If those breaks are not repaired properly, then it is possible those oocytes – cells that create eggs – never fully develop,” Libuda said.
A better prepared couple who carry the BRCA1 mutations can understand these mechanisms and the size they could influence on their fertility treatments finances and mental health. It may one day lead to more specific treatments.
You hear a lot of that — BRCA1 and women’s health, breast cancer, infertility — but it’s not just a woman’s problem. Now, Libuda’s team is studying how BRCA1 actually impacts sperm viability. In addition to this, they are looking into other genes involved in DNA repair when making eggs and sperm.
Libuda said their BRCA1 study is proof of principle that the technology they developed is a powerful system to understand such mechanisms. “Now we are looking at a whole bunch of other genetic players.”
Reference: BRCA1/BRC-1 and SMC-5/6 regulate DNA repair pathway engagement during Caenorhabditis elegans meiosis.
