Male factors play a role in 45% of infertility cases, WHO data shows
A World Health Organization study of 8,500 couples across 25 countries found that male factors contribute fully or partly to 45% of infertility cases, yet the biology of how male reproductive cells age remains poorly understood. A 2024 editorial in Nature Reviews Urology noted that the burden of male infertility is often unrecognized, its causes poorly understood, and men frequently marginalized during treatment.
A midlife “cliff” in mouse sperm RNA
The mix of small RNA fragments carried by mouse sperm changes abruptly in middle age: sperm heads from older mice contain longer RNA fragments and fewer short ones. The same pattern was later confirmed in human samples from two separate groups of donors, though that does not prove humans experience the same midlife cliff.
Chen described the finding as “like finding a molecular clock that ticks with aging in mice and humans,” adding that the gradual shift in fragment length may accumulate quietly until it triggers the midlife change in the aging trajectory.
Why sperm RNA matters beyond DNA
Scientists have known for decades that aging sperm accumulate DNA damage and genetic mutations, a phenomenon long used to explain declining male fertility. But sperm deliver more than DNA to the egg: they also carry RNA fragments, some picked up in the epididymis, the duct that transports sperm out of the testes. These fragments may regulate early embryonic development and can carry environmental traits to the next generation.
When RNA fragments resembling those in aged sperm were introduced into mouse embryonic stem cells, researchers observed changes in the activity of genes linked to metabolism and neurodegeneration. The researchers said the results reveal “a new picture of sperm aging” in mice and humans, heralding a new era in reproductive health.
What researchers plan to do next
Chen and colleagues now aim to identify the enzymes driving the RNA changes and determine whether they can be targeted. “If we can understand the enzymes that drive this shift, they could become intervention targets to improve sperm quality in older men,” Chen said. Pinning down the actual effects of these changes in humans will require further study.
Questions readers ask about sperm aging and RNA
No. Researchers confirmed the same RNA pattern in human samples from two separate donor groups, but that alone does not establish that humans go through the same midlife shift seen in mice.
In mice, injecting aged-sperm-like RNA fragments into embryonic stem cells altered genes tied to metabolism and neurodegeneration, suggesting a possible mechanism, but the real-world effects in humans remain unconfirmed.
Not yet. The study’s authors say identifying the responsible enzymes could open the door to future treatments, but no intervention exists today.
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