Weird self-harm in moms linked to ldl cholesterol

California two-spotted octopus

Like many octopuses, the California two-spotted octopus (Octopus bimaculoides) declines and dies quickly after breeding. Credit score: Tom Kleindinst, Marine Biology Laboratory

Modifications in ldl cholesterol manufacturing result in a tragic octopus dying spiral.

New analysis finds exceptional parallels within the biology of steroid hormones between cephalopods, mice and people that may have dire penalties when disturbed.

Regardless of their uncanny intelligence and seemingly supernatural skills to alter colour and regenerate their limbs, octopuses usually undergo tragic deaths. After laying a clutch of eggs, a mom octopus stops consuming and wastes away; by the point the eggs hatch, she is lifeless. Some females in captivity even appear to deliberately pace up this course of, mutilating themselves and twisting their arms in a tangled mess.

The supply of this weird maternal habits seems to be the optic gland, which is an organ much like the pituitary gland in mammals. How this gland triggered the horrific dying spiral has been unclear for years, however a brand new research by researchers from the[{” attribute=””>University of Chicago, the

Self-destruct hormones

In 1977, Brandeis University psychologist Jerome Wodinsky showed that if he removed the optic gland from Caribbean two-spot octopus (Octopus hummelincki) mothers, they abandoned their clutch of 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, then a graduate student at the University of Chicago, and Clifton Ragsdale, PhD, Professor of Neurobiology at UChicago, sequenced the RNA transcriptome of the optic gland from several California two-spot octopuses (Octopus bimaculoides) at different stages of their maternal decline. Mother Octopus

The optic gland of mother octopuses undergoes a massive increase in cholesterol production, which may trigger its bizarre reproductive behavior. Credit: Kathryn Knight, UChicago

In the new paper, published on May 12, 2022, in the journal Current Biology, Wang and Ragsdale took their studies a step further and analyzed the chemicals produced by the maternal octopus optic gland. They worked with Stephanie Cologna, PhD, Associate Professor of Chemistry at UIC, and Melissa Pergande, a former graduate student at UIC, who specializes in mass spectometry, a technique that analyzes the chemical composition of biological samples. Since Wang’s previous research pointed to increased activity in the genes that produce steroids, they focused on cholesterol and related molecules in the optic gland tissue.

They found three different pathways 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 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 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. “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,” Wang said. “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 (SLOS), 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.

Tiny and underappreciated

The findings suggest that disruption of the 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,” Ragsdale said. “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.”

Pygmy Zebra Octopus Hatchling (Octopus chierchiae)

Unlike many octopus species, the lesser striped octopus breeds multiple times. Credit: Tim Briggs, Marine Biological Laboratory

This summer, Wang will be studying at the UChicago affiliated Marine Biological Laboratory (MBL) as part of the Grass Fellowship, before she joins the faculty at the University of Washington. A major draw of MBL is their extensive cephalopod research program, in particular a new model animal, the lesser Pacific striped octopus (Ocotopus chierchiae). Among other useful features like its small, manageable size, the striped octopus doesn’t self-destruct after breeding like the animals Wang and Ragsdale have been studying so far. Wang plans to examine the striped octopus’s optic glands and compare them to her new results to look for clues as to how it avoids the tragic octopus 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 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.”

Reference: “Steroid hormones of the octopus self-destruct system” by Z. Yan Wang, Melissa R. Pergande, Clifton W. Ragsdale and Stephanie M. Cologna, 12 May 2022, Current Biology.
DOI: 10.1016/j.cub.2022.04.043

The study, “Steroid hormones of the octopus self-destruct system,” was supported by the National Science Foundation, the University of Illinois Chicago, the Illinois Board of Higher Education, and the Marine Biological Laboratory.