PULLMAN, Wash. — A father's health before conception may leave a biological imprint on his future children, according to a new study from Washington State University.
Published in Proceedings of the National Academy of Sciences , the study addresses a long-standing question in reproductive biology: How can a father's diet, metabolism or environmental exposures influence the health of his offspring when sperm contribute little more than DNA at fertilization? For many years, scientists have known paternal factors such as obesity, poor diet or metabolic disease can increase the risk of metabolic problems in the next generation. What has remained unclear is where that information is stored in sperm and how it is passed from father to offspring.
"Our study asks a very basic but important question," said Wei Yan, professor and director of the WSU School of Molecular Biosciences and senior author of the study. "If a father's metabolic condition can influence his offspring, where does that heritable information come from?"
The answer, according to the new work, points strongly to the testis, the organ where sperm are produced, rather than to later changes sperm may acquire during their journey through the male reproductive tract. This suggests a father's health before conception may help shape the biological environment that influences the earliest stages of life.
Unlike most cells in the body, mature sperm are highly compact and specialized for delivering paternal genetic material to the egg. Recent studies have proposed that sperm mitochondria, the energy-producing structures often called the "powerhouses" of the cell, might contain mitochondrial DNA that could actively produce RNA during sperm maturation. Those RNAs were thought to potentially alter sperm's small RNA cargo and influence offspring traits.
Yan's team found evidence against that model. The researchers showed that mature mouse sperm are effectively depleted of mitochondrial DNA, making it unlikely mitochondrial DNA-driven transcription in mature sperm is responsible for transmitting paternal metabolic information.
Instead, the study suggests the relevant information is established earlier, during sperm development in the testis.
To test this, the researchers used intracytoplasmic sperm injection, or ICSI, a technique in which sperm heads are injected directly into eggs. This allowed the team to compare sperm taken directly from the testis with sperm collected later from the epididymis, where sperm normally mature and are stored before ejaculation.
The distinction was important. If paternal metabolic information were acquired mainly during epididymal transit, then testicular sperm should not transmit the same effects. But the researchers found testicular sperm were capable of transmitting diet-associated metabolic traits to offspring, supporting the idea that the key information originates before sperm leave the testis.
"This is important because it shifts the focus upstream," Yan said. "It suggests the father's metabolic status can influence sperm during their formation in the testis, before sperm enter the epididymis."
The work does not mean metabolic disease is predetermined or unavoidable in children. Rather, it helps explain one possible biological pathway by which parental health before conception can influence disease susceptibility.
"This should not be interpreted as blame," Yan said. "It is about understanding biology. The more we understand how paternal health affects offspring, the better we can think about prevention, reproductive health and early-life disease risk."
Because sperm production takes time, the findings raise the possibility that improving paternal health before conception could have benefits not only for fathers but also for future children.
Yan said the study reflects a broader shift in reproductive biology.
"For a long time, maternal health has been the central focus of preconception and pregnancy research, and rightly so," he said. "But paternal health also matters. Our study helps explain how information from the father can be carried by sperm to the next generation."
