A breakthrough in understanding what causes male infertility

Newcastle University researchers have discovered a new genetic mechanism that might lead to severe male infertility.

This advancement in our understanding of the underlying causes of male infertility gives patients hope for better treatment options in the future.

New mutations, not inherited from father or mother, play a crucial role in this medical disease, according to a study published today in Nature Communications.

Experts have discovered that abnormalities that arise during the reproduction process, when both parents' DNA is duplicated, can lead to infertility later in life in men.

It is hoped that this new information will lead to further answers in the future about the cause of infertility and the best treatment options for infertile couples.

The study was directed by Professor Joris Veltman, Dean of Newcastle University's Biosciences Institute in the United Kingdom, and included patients from Newcastle Fertility Centre and Radboud University Medical Center in the Netherlands.

He stated, " "This is a significant shift in how we think about the causes of male infertility. The majority of genetic studies focus on recessively inherited causes of infertility, in which both parents are carriers of a gene mutation, and infertility arises when the son inherits both mutant copies, causing fertility issues." However, our research has discovered that mutations in parents' DNA that develop during reproduction play a substantial influence in their sons' infertility.

"At the moment, we don't know what's causing infertility in the majority of guys, and this research will hopefully increase the number of individuals for whom we have answers."

A global cohort of 185 infertile males and their parents' DNA was collected and analysed by scientists. They discovered 145 uncommon protein-altering mutations that are likely to affect male fertility negatively.

As many as 29 of the mutations impact genes that are directly involved in spermatogenesis (the generation of sperm cells) or other cellular processes associated to reproduction.

Experts discovered mutations in the RBM5 gene in a number of infertile guys. Previous study in mice has revealed that this gene is involved in male infertility.

Importantly, most of these mutations cause dominant infertility, which means that only one defective gene is required. As a result, there's a 50% risk that infertility induced by these mutations will be handed down to the man's child (if assisted reproductive technologies are utilized), which could lead to infertility, especially in boys.

As a result of infertility, millions of children have already been born using assisted reproductive technologies. According to this study, a large percentage of these children may inherit their father's sterility.

"If we can get a genetic diagnosis, then we can start understanding more about male infertility difficulties and why some infertile men still generate sperm that can be utilized successfully for assisted reproduction," Professor Veltman said.

"We believe that, using our data and those of others, physicians may improve couples' counselling and prescribe the optimal course of action for conceiving, either by offering an appropriate medically assisted technique or, if none is available, by providing adequate alternatives."

It is estimated that up to 7% of males suffer from infertility, and the guy is responsible for 50% of reproductive issues in heterosexual couples. The reason of male infertility is unknown in almost half of all instances.

Moving forward, the researchers hope to broaden their research by collaborating with a big multinational collaboration to investigate thousands of patients and their parents.