Octopuses typically die tragically, despite their remarkable intellect and almost magical capacity to change color and regrow limbs.

A mother octopus stops eating and loses away after laying a clutch of eggs; by the time the eggs hatched, she is dead.

Some captive females appear to hurry up this process on purpose, dismembering themselves and tangling their limbs into a tangled mess.

Self-destructing hormones
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The optic gland, which is comparable to the pituitary gland in mammals, appears to be the source of this strange maternal behavior.

Researchers from the University of Chicago, the University of Washington, and the University of Illinois Chicago (UIC) discovered that the optic gland of maternal octopuses experiences a major shift in cholesterol metabolism, resulting in substantial alterations in the steroid hormones produced, as per ScienceDaily.

They know cholesterol is essential from a nutritional standpoint, as well as within other signaling systems in the body, said Z. Yan Wang, Ph.D., is an Assistant Professor of Psychology and Biology at the University of Washington and the study's principal author.

It's engaged with everything from cell membrane flexibility to stress hormone synthesis, but it's surprising to see it play a role in this life cycle phase as well.

They discovered three distinct pathways for increasing steroid hormones: one that generates pregnenolone and progesterone (steroids commonly associated with pregnancy), another that generates maternal cholestanoids (intermediate components for bile acids), and the third that generates increased levels of 7-dehydrocholesterol (7-DHC), a precursor to cholesterol.

That latter one is particularly intriguing since excessive levels of 7-DHC are hazardous in humans and a characteristic of Smith-Lemli-Opitz syndrome (SLOS), a hereditary condition in which children suffer from severe developmental and behavioral repercussions, including recurrent self-injury.

These findings show that disrupting the cholesterol synthesis process is one stage in the female octopuses' self-destruct sequence, signaling further alterations downstream and eventually leading to their doom, as per Cosmopolitan magazine.

Wang, a graduate student at the time, and Clifton Ragsdale, PhD, Professor of Neurobiology at UChicago, sequenced the RNA transcriptome of the optic gland from multiple California two-spot octopuses (Octopus bimaculoides) during various phases of maternal decline in 2018.

Because RNA conveys DNA instructions on how to make proteins, sequencing it is a useful tool to understand gene activity and what's going on within cells at any given time.

As the animals began to fast and fall, there was increased activity in genes that metabolize cholesterol and create steroids, marking the first time that the optic gland was related to something other than reproduction.

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The findings imply that disrupting the cholesterol synthesis pathway in octopuses, as it does in other species, has serious implications.

So far, Wang and her colleagues have uncovered another phase in the octopus self-destruct cycle, signaling further alterations downstream that eventually lead to the mother's strange behavior and doom.

"What's startling is that they tend to go insane shortly before they die," Ragsdale explained. "Perhaps it's two processes, maybe three or four, but we now have at least three seemingly separate paths to steroid hormones that could explain the variety of impacts that these animals exhibit."

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

MBL's large cephalopod research program, particularly a novel model animal, the smaller Pacific striped octopus, is a key lure (Ocotopus chierchiae).

The striped octopus, unlike the organisms Wang and Ragsdale had previously studied, does not self-destruct after reproducing, among other advantages.

Wang intends to analyze the optic glands of the striped octopus and compare them to her recent findings to find out how it escapes the sad octopus death cycle.

Related article: Octopus Farming Raises Ethical Concerns: Do These Clever Cephalopods Have Emotions