Scientists may have finally figured out a genetic cause of male infertility.
Researchers at Newcastle University in the United Kingdom published their study in Nature Communications in early January 2022. Led by Professor Joris Veltman, the Dean of Newcastle University’s Biosciences Institute, the team investigated the potential genetic causes of male infertility. They found 145 rare, protein-affecting mutations that are the likely culprits.
Infertility experts estimate that 7% of people with male reproductive organs have male infertility, causing approximately half of the infertility issues experienced by heterosexual couples. 50% of these male infertility cases have unexplained causes. Identifying genetic causes of such a condition could help to explain this phenomenon and provide insight into potential treatments for it.
The research team studied the DNA of 185 infertile men and their unaffected parents, the cohort including patients from around the world. They discovered 145 mutations that alter proteins and likely contribute to male infertility. Of the mutations, 29 were involved in creating the sperm (spermatogenesis).
They observed a large amount of loss of function mutations in genes that were intolerant to loss of function mutations compared to fertile men's genetic profile. They also identified mutations in RMB5, a gene that has been previously implicated as a cause of male infertility in studies done with mice. This gene regulates pre-mRNA splicing in male germ cells, making it a likely candidate for a cause of infertile sperm.
The research team also found that most of the mutations occur in the reproduction process. These specific mutations are genetically dominant, different from the recessive genetic causes that have been investigated in the past. Studying recessive mutations has implied that a child had to inherit two mutated copies of a gene, one from each parent, to have this condition. This has significant implications for the inheritance of male infertility.
“Our research has found that mutations which occur when the DNA is replicated during reproduction in parents play a significant role in the infertility in their sons,” Veltman said in the press release.
The research team already has its sights set on future studies, including ones with larger populations spanning the globe. They also want to delve further into the mutated genes they have already identified and determine their effects on spermatogenesis.
The research suggests that there is a possibility some children could inherit infertility using reproductive technologies. Veltman and his team advise that couples who seek alternative solutions to male infertility should consult with their doctors about the risk of transmitting the condition to their children.
“We hope clinicians can improve counseling for couples and recommend what is the best course of action to conceive, either by proposing an appropriate medically-assisted procedure or in cases where none is suitable, provide appropriate alternatives,” he said.