Some mice have a cheating heart. It’s a hormonal thing, scientists find.


The deer mouse, believed to be the most common mammal in North America, has a very different take on family values than its evolutionary sibling, the oldfield mouse.

Oldfield mice are monogamous. Fathers groom their young, keep them warm and ensure they don’t wander far from the nest. The deer mouse prefers the swinging lifestyle when it comes to sexual partners. It’s not unusual for the pups in a single litter to come from four different fathers. As for the deer mouse dads, they’re downright negligent. Nothing, it seemed, could bring out the warm and fuzzy dad behavior.

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Until now. Researchers at Columbia University investigating the two species of mice discovered what appears to be a crucial difference: Oldfield produce an adrenal cell not found in other mice. The cell makes a hormone, which, when injected into virgin deer mice of both sexes, spurred 17 percent – even males – to groom their young and keep them close to the nest.

Alas, it had no effect when it came to the deer mouse’s preference for playing the field with multiple female partners.

It didn’t make them want to spend more time with their mate, said Andrés Bendesky, one of the authors of a paper published Wednesday in the journal Nature describing the research.

By examining other species of mice, Bendesky and his team determined that the newly discovered cell type had developed in oldfield mice about 20,000 years ago, essentially “the blink of an eye” on the evolutionary time scale.

While parenting and monogamy are distinct characteristics, they are connected in biology, said Bendesky, a principal investigator at Columbia’s Zuckerman Institute.

The vast majority of mammals – 92 percent, according to Bendesky – are promiscuous like the deer mouse. When female deer mice are in heat, they sometimes mate with multiple males on the same night, allowing different fathers to fertilize different eggs.

In most promiscuous species, males do not participate in the care of the young. Bendesky said there are only three outliers; promiscuous species in which the males actually help with parenting: the banded mongoose, the gray bamboo lemur and Goeldi’s monkey.

“All three are derived from a recently monogamous ancestor,” Bendesky said, “underscoring the close and enduring link” between monogamy and shared parenting.

The subject of monogamy in the animal kingdom remains controversial, with some scientists maintaining that as few as 3 to 5 percent of mammals are monogamous.

Researchers refer to two distinct kinds of monogamy: social monogamy, in which partners mate and live together for one or more breeding seasons; and genetic monogamy, in which couples mate with one another exclusively.

Varying theories exist about the evolutionary benefit that monogamy bestows upon males. Some scientists maintain that staying home with a mate, rather than prowling for other females, might have been a way to keep competing males from snacking on the offspring. An alternative explanation is that males simply found it much easier to keep rival males away from one female, rather than several.

Bendesky, who has been studying the difference between oldfield and deer mice for 12 years, said he found an unexpected clue in the anatomy of the two species. Each of the two oldfield mouse adrenal glands weighs 7 milligrams ― more than four times heavier than that of deer mice.

“It’s massive,” Bendesky said of the difference. When scientists have bred mice to display more or less anxiety – a feeling derived from hormones manufactured in the adrenal gland – they never found a difference in gland size of more than 20 percent.

The adrenal glands are one of the main sources of steroid hormones, which act as important controllers of behavior, including parental care. The great difference in adrenal size suggested the oldfield mice were producing more of at least some of the steroid hormones.

When the scientists looked more closely at the differences between the species, they discovered that each adrenal gland in the oldfield mouse has four layers or zones, instead of the three in the deer mouse. It is the fourth, dubbed the zona inaudita (Latin for “previously unheard-of zone”) that contains the new adrenal cell.

Scientists established that the newly discovered cell was different from other adrenal cells by performing genetic analysis. They found 194 genes were turned up higher in the newly discovered cells than in other cells. The activity level of genes can be turned up or down, just as a light can be adjusted with a dimmer switch.

In the newly discovered cells, oldfield mice make a hormone called 20 alpha-hydroxyprogesterone (20alpha-OHP), which was discovered in humans in 1958.

“But nobody knew what it really does in humans,” Bendesky said.

In that sense, the hormone was much like the organ that produced it. The adrenal gland, first described in 1564, was such a puzzle to scientists that in 1716, the Academy of Sciences of Bordeaux sponsored an essay competition to determine what purpose the organ served. No entry was deemed worthy of the prize.

Only much later did discovery of diseases such as adrenal insufficiency help clarify its role in producing hormones involved with regulating metabolism, immunity, blood pressure and response to stress.

The research by Bendesky and his colleagues disclosing the new cell type surprised other scientists.

“It’s extraordinary,” said Steven M. Phelps, a professor of integrative biology at the University of Texas at Austin, who was not involved in the study but has been following Bendesky’s work on deer and oldfield mice for some time. “The most exciting piece is the origin of what seems to be a new cell type.”

Phelps said it marked the first time in his 30 years in the field that he could remember such a discovery of a new cell type.

“What was really exciting to me about the paper was the idea that this hormone produced in the adrenal gland” then is broken down and used in the brain to affect caregiving behavior, said Jessica Tollkuhn, associate professor at Cold Spring Harbor Laboratory, who was not involved in the study.

“This is really a new aspect of biology that had not been described before,” Tollkuhn said.

Margaret M. McCarthy, professor of pharmacology at the University of Maryland School of Medicine, expressed surprise that evolution instilled parenting behavior in such a complex manner. Regulating the brain with a hormone forged in the adrenal gland, she said, was less direct than simply developing a new neural circuit.

“That’s what has happened in voles where you have the monogamous and non-monogamous voles,” McCarthy said, referring to the small rodents sometimes mistaken for mice. “Evolution always surprises. There’s a million ways to solve a problem.”

The findings in mice may lead to insights when it comes to parenting behavior in humans, scientists said.

In mice, the parenting hormone often gets converted into a compound that closely resembles allopregnanolone, which was approved by the Food and Drug Administration in 2019 to treat postpartum depression. The medication is known as brexanolone and sold under the brand name Zulresso.

Tali Kimchi, an associate professor at Weizmann Institute of Science in Israel, said by email that the Nature paper raises the possibilities for deeper research into postpartum depression, “one of the most devastating, incurable psychopathologies we know, with long-lasting and sometimes even lethal effects on both parents and offspring.”

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