UW News

May 12, 2022

Changes in cholesterol production lead to tragic octopus death spiral

A mother California two-spot octopus, Octopus bimaculoides, near the end of her life.Z Yan Wang

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

The source of this bizarre maternal behavior seems to be the optic gland, an organ similar to the pituitary gland in mammals. For years, just how this gland triggered the gruesome death spiral was unclear. 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 Chicago show that the optic gland in maternal octopuses undergoes a massive shift in cholesterol metabolism, resulting in dramatic changes in the steroid hormones produced. Alterations in cholesterol metabolism in other animals, including humans, can have serious consequences on longevity and behavior, and the team believes this reveals important similarities in the functions of these steroids across the animal kingdom — in soft-bodied cephalopods and vertebrates alike.

“We know cholesterol is important from a dietary perspective, and within different signaling systems in the body, too,” said lead author Z Yan Wang, an incoming assistant professor of psychology and of 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 production of stress hormones, but it was a big surprise to see it play a part in this life cycle process as well.”

In 1977, Brandeis University psychologist Jerome Wodinsky showed that if he removed the optic gland from Caribbean two-spot octopus mothers, they abandoned their eggs, resumed feeding, and lived for months longer. At the time, cephalopod biologists concluded that the optic gland must secrete some kind of “self-destruct” hormone, but just what it was and how it worked was unclear.

In 2018, Wang and Clifton Ragsdale, a University of Chicago professor of neurobiology, identified which genes are switched on and which ones are switched off in several California two-spot octopuses — Octopus bimaculoides — at different stages of their maternal decline. As the animals began to fast and decline, there were higher levels of activity in genes that metabolize cholesterol and produce steroids, the first time the optic gland had been linked to something other than reproduction.

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

They found three different biochemical pathways were involved in increasing steroid hormones after reproduction. One of them produces pregnenolone and progesterone, two steroids commonly associated with pregnancy. Another produces maternal cholestanoids, or intermediate compounds for making      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 the stages of decline. While the pregnancy hormones are to be expected, this is the first time anything like the components for bile acids or cholesterol have been linked to the maternal octopus death spiral.

Some of these same pathways are used for producing cholesterol in mice and other mammals as well, according to Wang.

“There are two major pathways for creating cholesterol that are known from studies in rodents, and now there’s evidence from our study that those pathways are probably present in octopuses as well,” said Wang. “It was really exciting to see the similarity across such different animals.”

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

The findings suggest that disruption of cholesterol production process in octopuses has grave consequences, just as it does in other animals. So far, what Wang and her team have discovered is another step in the octopus self-destruct sequence, signaling more changes downstream that ultimately lead to the mother’s odd behavior and demise.

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

A newly hatched lesser Pacific striped octopus, Octopus chierchiae, with a pencil eraser for scale.Tom Briggs/Marine Biological Laboratory

Wang has earned a Grass Fellowship to conduct research this summer at the University of Chicago’s Marine Biological Laboratory in Woods Hole, Massachusetts. There, she will study the optic gland of another species, the lesser Pacific striped octopus, or Octopus chierchiae. This species doesn’t self-destruct after breeding like the animals Wang and Ragsdale have been studying so far. Wang hopes to find clues as to how it avoids the octopus death spiral.

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

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

For more information, contact Wang at zywang22@uw.edu.

Adapted from a press release by the University of Chicago.