Tragic death spiral of octopus mothers caused by changes in cholesterol production

Octopuses are known for their uncanny intelligence, but the bizarre behaviour of some female octopuses seems a contradiction: after a female octopus lays a clutch of eggs, she stops eating and wastes away.

By the time her babies hatch she’s already dead. Some female octopuses in captivity even seem to speed up this process intentionally by mutilating themselves and twisting their arms into a tangled mess.

Scientists have known for decades that the source of this gruesome self-destruct system seems to be the female octopuses’ optic gland – their equivalent of the pituitary gland – but haven’t understood just how its triggered.

Now, a new study in Current Biology has revealed that the optic gland undergoes a massive shift in cholesterol metabolism during reproduction, resulting in dramatic changes in the steroid hormones produced.

“We know cholesterol is important from a dietary perspective, and within different signalling systems in the body too,” says lead author Z. Yan Wang, assistant professor of psychology and biology at the University of Washington, US. “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, research showed that if the optic gland is removed from female Caribbean two-spot octopus (Octopus hummelincki), they abandon their clutch of eggs, resume feeding, and live for months longer than usual.

More recently, Wang and co-author Clifton Ragsdale – professor of neurobiology at the University of Chicago, US – found that as California two-spot octopus (Octopus bimaculoides) mothers begin to fast and decline, there are higher levels of activity in genes involved in metabolising cholesterol and producing steroids.

Building on this, the team have now analysed the chemicals produced by the maternal bimaculoides optic gland after reproduction, using a technique called mass spectroscopy that can analyse the composition of biological samples.

The female octopuses’ self-destruct sequence

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

That last one is particularly interesting because elevated levels of 7-DHC are toxic in humans and a hallmark of a genetic disorder, Smith-Lemli-Opitz syndrome (SLOS), in which children suffer from severe developmental and behavioural consequences, including repetitive self-injury.

These findings suggest that the disruption of the cholesterol production process is one step in the female octopuses’ self-destruct sequence that signals more changes downstream, ultimately leading to their demise.

“What’s striking is that they go through this progression of changes where they seem to go crazy right before they die,” says 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.”

Wang now plans to study the optic glands of a new animal model, the lesser Pacific striped octopus (Ocotopus chierchiae) which doesn’t self-destruct after breeding, 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 says. “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.”