Sperm Can Carry Dad's Stress as Well as Genes

You know the drill. All of our cells contain 23 pairs of chromosomes, except for eggs and sperm; they contain one of each pair, joining forces at fertilization.

Compared with eggs, sperm have an unexciting role in this process. For starters, they have almost no mitochondria, the powerhouses of the cell. But mitochondria also contain DNA, genes of their own. Thus, essentially, all "mitochondrial DNA" is inherited from the female.

Moreover, in an egg (and other non-sperm cells), frenzied activity goes on around the DNA, as proteins called transcription factors turn genes on and off, and as gene products go through quality control, with things called micro-RNAs acting as a filter. But in sperm, dogma holds that genes are inactive; a sperm is just an inert delivery system. It might as well be an Amazon drone delivering 23 unpaired socks.

Thus, sperm seemed irrelevant to discoveries in the field of epigenetics, which has revolutionized our concept of how traits are handed down. What do you inherit from your mother? Genes. But you also can inherit ways in which regulation of her genes has been altered by experience and the environment. Such influences can freeze the on-off switch for some gene in one position. Moreover, environmental influences can permanently silence genes, either by destroying transcription factors that activate them or, indirectly, through these still-mysterious micro-RNAs.

In other words, while environment rarely changes the DNA sequence of a gene (i.e., a "mutation"), it can cause epigenetic changes in the gene's regulation. And if that occurs in an egg, such epigenetic markers can be passed to offspring, resulting in "nongenetic transmission of traits." There can be mother-to-child nongenetic transmission of traits related to the normal workings of the body, behavior and propensities toward certain diseases.

Meanwhile, over in Boring-ville, epigenetic markers appeared to be erased in sperm, precluding them from transmitting anything except genes. Naturally, this is turning out to be wrong.

In a recent paper in the Proceedings of the National Academy of Sciences USA, Qing-Yuan Sun of the Chinese Academy of Sciences and colleagues used a drug to make male mice prediabetic. And unexpectedly, their offspring also became prediabetic as adults.

Was this due to the fathers' behavior around their offspring? No—the males were there solely for mating. Instead, becoming prediabetic caused epigenetic silencing of some genes in the pancreas of these males (an organ centrally involved in diabetes). And the same epigenetic changes occurred in their sperm as well, also affecting their offspring's pancreases.

This applies to behavior too, as reported in a recent paper in Nature Neuroscience by Isabelle Mansuy of the University of Zurich and colleagues. Prior work showed that if you stressed young male mice, as adults, they differed from control mice in how readily they explored a new environment and how quickly they gave up trying to cope with a challenging task (findings pertinent to understanding anxiety and depression).

Critically, the offspring of those males showed the same behaviors. Again, Dad wasn't doing any parenting. Instead, the stressful upbringing caused epigenetic changes (due to those micro-RNAs) in sperm. In a tour de force, the authors injected micro-RNAs from sperm of stressed males into fertilized eggs—passing on the behavioral trait. Thus, early life stress changed adult behavior of male mice, who passed it on to their offspring via epigenetic changes in their sperm.

What's interesting about this? Well, for one thing, it demonstrates further how the environment can alter biology with multigenerational influences. But more specifically, sperm, and the lifestyles of the organisms that make them, play a larger role in these processes than previously thought.


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