The sperm is not a passive supplier of genetic material to the egg. A study from Linköping University, Sweden, shows that certain molecules that come with the sperm, so-called micro-RNA, contribute to the development of the embryo several days after conception. The findings, published in the journal Nature Communications, may in the long term contribute to better diagnosis and treatment of involuntary childlessness.

“It seems that sperms can help with embryo development by bringing other molecules with them, in addition to DNA. These molecules aid in starting embryo development. So you can say that the sperm, or the male part of conception, has a greater significance than was previously understood,” says Anita Öst, professor of cell and molecular biology at Linköping University, who led the study.

Many couples are affected by involuntary childlessness, or infertility. About one in six people suffer from infertility. For some, it is possible to become pregnant through what is known as in vitro fertilisation, IVF, which takes place outside the body. The fertilised eggs are then transferred to the uterus and hopefully lead to pregnancy. Embryo quality is one of the major limiting factors for successful IVF treatment. Improved early embryo quality assessment could increase chances that IVF treatment leads to pregnancy.

But one third of those undergoing IVF treatment are found to have unexplained infertility. Today’s IVF treatment focuses mainly on the woman and on hormonal stimulation to make several eggs mature at the same time, to be retrieved and fertilised by the man’s sperm. At the same time, sperm quality has fallen in many countries in recent decades, for unknown reasons.

In the current study, the LiU researchers wanted to explore factors linked to the man that can affect whether the IVF treatment is successful or not. Sixty-nine couples undergoing IVF treatment at Linköping University Hospital donated surplus sperm. The researchers purified RNA from the sperm and analysed them. They then compared the presence of different RNA molecules with sperm concentration and mobility, ability to fertilise an egg, embryo quality and whether the pregnancy resulted in a baby.

It turned out that larger amounts of some very short pieces of RNA, called micro-RNA, in the man’s sperm bode well for the formation of an embryo and its development.

“A particularly interesting finding was that from the sperm sample we could in principle predict the effect it would have on the embryo quality several days later. We found some RNAs that seem important for sperm to be able to fertilise the egg, and other micro-RNA significant for the embryo to develop well,” says Signe Isacson, bioinformatician and one of the researchers behind the study.

Micro-RNA has been shown to have important gene-regulating functions in cells. Previous studies have indicated that some micro-RNA in sperm affects embryo development in animals, but research in humans is very limited. The current study is important because it indicates clinical relevance for fertility in humans.

“The specific molecules we found are good candidates for being markers of whether a man’s sperm gives good embryo quality or not. The findings can in the long term contribute to better understanding and diagnostics, which in the future may improve couples’ chances to have children,” says Kajsa Karlsson, PhD student at LiU and physician.

But why do some men have a lot of these micro-RNAs while others have less? Scientists don’t know yet. It is also unknown whether micro-RNA is formed in the sperms or comes from the testes or the epididymis, where they are stored. Another question is whether micro-RNA amounts are affected by lifestyle. An ongoing study conducted by the researchers investigates whether it makes any difference if the man eats healthy food, developed by a dietician, during IVF treatment.

Micro-RNA came into the spotlight when the Nobel Prize in Medicine or Physiology in 2024 was awarded to the scientists who discovered the existence of micro-RNA. The discovery was made in the small worm C. elegans. Today, more than a thousand different micro-RNAs in humans are known.

“The micro-RNA that appeared in our study belongs to the same family the discovery of which was awarded the Nobel Prize. Those scientists found them because they are necessary for embryo development in worms. I found it very surprising that similar micro-RNA in human sperm also seems to be necessary for embryo development,” says Anita Öst.

The study was funded with support from the Swedish Research Council, the Ragnar Söderberg Foundation, the Knut and Alice Wallenberg Foundation and Region Östergötland.

Article: Small RNA in sperm – Paternal contributions to human embryo development, Signe Isacson, Kajsa Karlsson, Stefan Zalavary, Anna Asratian, Unn Kugelberg, Susanne Liffner and Anita Öst, (2025), Nature Communications, published online 17 July 2025, doi: https://doi.org/10.1038/s41467-025-62015-2