What causes the octopus death spiral? New study indicates changes in cholesterol production

“We know that cholesterol is important from a dietary standpoint, and in different signaling systems in the body as well,” said study lead author Z. Yan Wang, PhD’18, a former from UChicago who will soon be an assistant professor at the University of Washington. “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.”

Self-destruct hormones

In 1977, Brandeis University psychologist Jerome Wodinsky showed that if he removed the optic gland from the Caribbean two-spotted octopus (Octopus hummelinki) mothers, they abandoned their brood, resumed feeding, and lived 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.

As a 2018 graduate student, Wang worked with Professor Clifton Ragsdale at UChicago to sequence the RNA transcriptome of the optic gland of several California two-spotted octopuses (bimaculoid octopus) at different stages of their maternal decline. RNA contains DNA’s instructions on how to make proteins, so sequencing is a good way to understand gene activity and what’s going on inside cells at any given time. 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 newspaper, published on May 12 in Current biology, Wang and Ragsdale took their studies a step further and analyzed the chemicals produced by the optic gland of the maternal octopus. They worked with UIC associate professor of chemistry Stephanie Cologna and former UIC graduate student Melissa Pergande, who specialize in mass spectrometry, a technique that analyzes the chemical composition of biological samples. Since Wang’s previous research showed increased activity in genes that produce steroids, they focused on cholesterol and related molecules in optic gland tissue.

They found three different pathways 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 components for bile acids, and the third produces increased levels of 7-dehydrocholesterol (7-DHC), a precursor to cholesterol.

The new research shows that the maternal optic gland undergoes dramatic changes to produce more pregnenolone and progesterone, maternal cholestanoids and 7-DHC 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. “There are two main pathways of cholesterol creation that are known from rodent studies, and now there is evidence from our study that these pathways are likely also present in octopuses,” 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 (SLOS), 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.

Tiny and underrated

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 explain the multiplicity of effects these animals show.

This summer, Wang will study at the UChicago-affiliated Marine Biological Laboratory (MBL) as part of the Grass Fellowship, before joining the faculty at the University of Washington.

A major attraction of MBL is their extensive research program on cephalopods, in particular a new model animal, little pacific striped octopus (Ocotopus chierchiae). Among other useful characteristics like its small, manageable size, the striped octopus does not self-destruct after breeding like the animals Wang and Ragsdale have studied so far. Wang plans to examine the striped octopus’ optic glands and compare them to her new findings to look for clues as to how she avoids the octopus’ tragic death spiral.

“The optic gland exists in all other soft-bodied cephalopods, and they have such divergent reproductive strategies,” she 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.”

Quote : “Octopus Self-Destruct System Steroid Hormones», Wang et al., Current biologyMay 12, 2022.

Funding: National Science Foundation, University of Illinois at Chicago, Illinois Council on Higher Education, Marine Biological Laboratory.

—A version of this story was first published by the Biological Sciences Division.

#octopus #death #spiral #study #cholesterol #production

Leave a Comment

Your email address will not be published. Required fields are marked *