An overlooked organ may help the ovary function

When an expansive curlicue of tissue sitting below the ovaries was discovered more than a century ago, it was dismissed as useless and erased from biology textbooks. Biologists now are taking a new look at the structure and its potential role.

The rete ovarii seems to communicate with the ovary by directing a flow of protein-packed fluids through its long, tubular structure into the organ, researchers report March 19 in eLife. The results come amid recent reports suggesting that the “rediscovered” appendage may be responding to the body’s hormonal signals. While still a hypothesis, the finding indicates that this complex structure may play a role in fertility and ovarian maintenance.

When the structure was first identified in 1870, it had no obvious purpose, so scientists deemed it a functionless remnant of development. And it remained practically ignored for over a century, with researchers focusing on parts of the ovary already known to be biologically useful.

It wasn’t until developmental biologist Jennifer McKey, then at Duke University, was imaging mouse ovaries in their entirety that she noticed a peculiar shape curving at the bottom of the ovary, like a horseshoe. She rooted through old literature until she matched her ovarian horseshoe with the long-forgotten rete ovarii.

In a 2024 Scientific Data paper, McKey, now at the University of Colorado in Aurora, and colleagues analyzed RNA in the rete ovarii to determine which genes are switched on and off — and if any are connected to ovarian function in mice. The researchers found a number of genes turned on when estrogen hormones were at their highest. For example, a protein associated with egg cell maturation and follicle maintenance was not only secreted by the rete ovarii, but also activated alongside increases in estrogen. This indicates that the rete ovarii may be responding to the hormone cycle in ways that are essential for fertility, says team member Dilara Anbarci, a developmental biologist at the University of Michigan in Ann Arbor.

New experiments suggest the rete ovarii secretes protein-filled fluid directly to the ovary, serving as a conduit between the larger ovarian environment and the organ. Using a fluid called dextran, whose molecules are too large to passively ooze through tissue, the team tracked an active exchange of fluid through the rete ovarii into the ovary.

That area is packed with blood vessels and nerves, suggesting that the rete may be able to sense information from the body. Anbarci likens the rete ovarii to an antenna: As hormones fluctuate, the rete perks up, tuning in to ovarian signals and secreting proteins based on the ovary’s needs.

These experiments show “there’s something going on,” says developmental biologist Serge Nef of the University of Geneva, who was not involved in the work. But “it’s just the beginning of the story…. Whatever it is, is it important for ovarian function?” More experiments need to be done to show that fertility is affected if the rete is removed or shut down, and if the rete ovarii functions similarly in humans.

“There’s still so much we can’t even begin to comprehend about female anatomy,” Anbarci says. “I hope this encourages more investigation in reevaluating what we don’t already know about the ovary.”