Sexy male mice have competitive moms

What makes a male mouse a stud? Allowing his mom to have a social life. A new study shows that parental experience can affect the reproductive abilities of offspring without any change to the DNA. Instead, quicker changes are involved, adding another finding that may be attributed to the growing field of epigenetics.

“It wasn’t what we set out to discover,” says study coauthor Wayne Potts of the University of Utah. Instead, he and colleagues were interested in why female mice produce sexually superior sons when given a choice between two males. The researchers thought the reproductive advantage might be related to testosterone levels. 

In an effort to give female mice plenty of choices, they set up mousey playgrounds, large enclosures divided with mesh, plastic caves, small holes and nesting materials. Ten male mice and 20 female mice were released into each enclosure. In this social environment, females would have to compete for the attention of the males, and the males would have to compete for territory. Control mice were bred in standard one-on-one mouse cages.

Compared with the mice in the laboratory cage, the female mice in the social environment produced male offspring that were better ladies’ men. The social moms’ sons got all the girls, but they also lived hard and died young, paying a price for their studliness, the scientists report November 18 in the Proceedings of the National Academy of Sciences.

What makes these ‘ladies’ mice’ so effective? They didn’t have differences in testosterone. Instead, the sexy sons produced more MUPs, major urinary protein pheromones (aka the brown gunk underneath the mouse in the photo). Mice “smell” these chemical markers through their vomeronasal organs, an organ which is vestigial in humans. Males produce far more MUPs than females, and they use them for marking territory with their urine. The pheromones also play a role in attracting mates. Female mice spend longer sniffing at highly concentrated  MUPs compared to lower concentrations, and are more likely to mate with male mice that have lots of MUPsto spray around.

But what causes these sons to produce so many attractive MUPs? In a single generation, it is unlikely that drifting genes could have caused the effect. Instead, the authors looked to epigenetics.

Epigenetics involves changes made to DNA that are not changes in the DNA sequence. Chemical “notations” can be added on to DNA sequences, and these notations make the genes near them more or less likely to be expressed as proteins. So for example, adding methyl groups on to some genes can make them less likely to be turned on. Taking methyl groups off, then, increases the gene’s expression, resulting in more protein produced. In this case, mothers who had been living socially produced male offspring who had decreased methylation on the MUP11 gene. The decreased methylation means the boys had higher levels of the MUP11 protein.

So going social doesn’t just change who a female mates with, it also changes the protein expression of her sons. In a social environment with lots of mating competition, higher levels of MUPs mean attracting more mates.

But producing MUPs is a high energy prospect. And it may come with a tradeoff: The sons of the social moms didn’t live as long. But for the increased reproductive success, it may be worth it. Live hard, die young.

In addition to the epigenetic findings, the study shows that the domestication of mice under controlled lab conditions, even those that have only been in the lab for a few generations, can become very different animals from their wild counterparts.

Potts says that the results may be an example of how epigenetics can be used to quickly adapt to different situations. “If animals routinely find themselves in situations that require very different gene expression profiles,” he says, “you might get a trigger. If social conditions mean upregulation of MUPsare useful, then a signal may trip for demethylatingMUPs in the offspring.” In the case of caged laboratory mice that don’t have to compete for mates, Potts says, “they don’t want to spend energy on useless social signaling.” So the genes that control the expression of their MUPs get methylated, reducing expression of the pheromones.

Lee Drickamer, a professor emeritus at Northern Arizona University who was not involved in the research, says that the findings have interesting implications, particularly for how we have domesticated laboratory mice. “It’s interesting to think of how animals really behave,” he says, “and how the domestication process itself might be a mediating factor.” As mice live in controlled environments without competition, they may need fewer MUPs. The effects of soft living.

It will be interesting to see the future studies on this topic. How do these epigenetic changes get to the eggs, for example? What in the eggs changes, if anything? Could these changes become more permanent, and if they did, how would it happen? The mice used had been domesticated a little already, bred in house for eight generations. What if “real” wild mice were used?  How exactly do MUPs change life span?

They are all interesting questions. Someday, we may know why more MUPs help you live fast and die young. But it’s a start to know that it all begins with mom having a bit of a social life.