Changes in Cholesterol Production Lead to Tragic Octopus Death Spiral

Newswise – For all their uncanny intelligence and seemingly supernatural abilities to change color and regenerate limbs, octopuses often suffer tragic deaths. After a mother octopus lays a clutch of eggs, she stops eating and wastes away; by the time the eggs hatch, she is dead. Some females in captivity even seem to intentionally speed up this process, mutilating themselves and twisting their arms in a tangled mess.

The source of this bizarre maternal behavior appears to be the optic gland, an organ similar to the pituitary gland in mammals. For years it was unclear how this gland triggered the horrible death spiral. But in a new study published May 12 in Current Biology, researchers from the University of Washington, the University of Chicago and the University of Illinois at Chicago show that the optic gland of maternal octopuses undergoes a change massive cholesterol metabolism, resulting in dramatic changes in the steroid hormones produced. Alterations in cholesterol metabolism in other animals, including humans, can have serious consequences for longevity and behavior, and the team believe this reveals important similarities in the functions of these steroids across the kingdom. animal – in soft-bodied cephalopods and vertebrates.

“We know that cholesterol is important from a dietary standpoint, as well as in different signaling systems in the body,” said lead author Z Yan Wang, incoming assistant professor of psychology and biology at the University of Washington, who initiated this study as a doctoral student at the University of Chicago. “It’s involved in everything from the flexibility of cell membranes to the production of stress hormones, but it was a big surprise to see it play a role in this life cycle process as well.”

In 1977, Brandeis University psychologist Jerome Wodinsky showed that if he removed the optic gland from two-spotted Caribbean octopus mothers, they would drop their eggs, resume feeding, and live for months longer. At the time, cephalopod biologists concluded that the optic gland must secrete some sort of “self-destructing” hormone, but what it was and how it worked was unclear.

In 2018, Wang and Clifton Ragsdale, professor of neurobiology at the University of Chicago, identified which genes are turned on and which are turned off in several California two-spotted octopuses – bimaculoid octopus — at different stages of their maternal decline. As the animals began to fast and decline, there were higher levels of activity in the genes that metabolize cholesterol and produce steroids, the first time the optic gland was linked to anything other than reproduction.

In the new paper, Wang and Ragsdale worked with UIC associate professor of chemistry Stephanie Cologna and former UIC graduate student Melissa Pergande to analyze the chemicals produced by the maternal octopus’ optic gland – focusing on cholesterol and related molecules.

They found that three different biochemical pathways were involved in the rise in steroid hormones after breeding. One of them produces pregnenolone and progesterone, two steroids commonly associated with pregnancy. Another produces maternal cholestanoids or intermediate compounds to make bile acids. The third produces increased levels of 7-dehydrocholesterol, or 7-DHC, a precursor to cholesterol.

The new research shows that the maternal optic gland undergoes dramatic changes to produce more steroid hormones during decline phases. While pregnancy hormones are to be expected, this is the first time that something like the components of bile acids or cholesterol have been linked to the death spiral of the maternal octopus.

Some of these same pathways are also used to produce cholesterol in mice and other mammals, according to Wang.

“There are two main pathways of cholesterol creation that are known from studies in rodents, and now there is evidence from our study that these pathways are likely present in octopuses as well,” Wang said. “It was really exciting to see the similarity between such different animals.”

High levels of 7-DHC are toxic in humans; It’s the hallmark of a genetic condition called Smith-Lemli-Opitz syndrome, which is caused by a mutation in the enzyme that converts 7-DHC to cholesterol. Children with this disorder suffer severe developmental and behavioral consequences, including repetitive self-harm reminiscent of octopus end-of-life behaviors.

The results suggest that disrupting the cholesterol production process in octopuses has serious consequences, just like in other animals. So far, what Wang and his team have discovered is another step in the octopus’ self-destruct sequence, signaling more downstream changes that ultimately lead to the strange behavior and death of the mother.

“What’s striking is that they go through this progression of change where they seem to go crazy right before they die,” Ragsdale said. “It’s maybe two processes, maybe three or four. Now we have at least three seemingly independent pathways to steroid hormones that could account for the multiplicity of effects these animals show.

Wang won a Grass Fellowship to conduct research this summer at the University of Chicago Marine Biology Laboratory in Woods Hole, Massachusetts. She will study the optic gland of another species, the small Pacific striped octopus, or Octopus chierchiae. This species does not self-destruct after breeding like the animals Wang and Ragsdale have studied so far. Wang hopes to find clues as to how he avoids the octopus’ death spiral.

“The optic gland exists in all other soft-bodied cephalopods, and they have such divergent reproductive strategies,” Wang said. “It’s such a small gland and it’s underappreciated, and I think it will be exciting to explore how it contributes to such a wide variety of life history trajectories in cephalopods.”

The research was funded by the National Science Foundation, the University of Illinois at Chicago, the Illinois Council on Higher Education, and the Marine Biological Laboratory.

Adapted from a Press release by the University of Chicago.

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