For years, a mysterious tangle of tissue lurking beneath the ovary has been dismissed, absent from anatomy charts and medical textbooks. But a new study suggests that this tissue, long thought to be a mere evolutionary baggage, may be much more important to fertility than anyone thought.

Called the rete ovarii, the structure was first spotted in 1870. With no clear function, researchers labeled it as vestigial. That classification has endured for generations. Until now.

In a study published in eLife, scientists led by developmental biologist Dilara Anbarci at the University of Michigan have brought this neglected structure back into the spotlight. Using advanced imaging, genetic analysis, and protein-tracking techniques in mice, the team uncovered evidence that the rete ovarii is not only active but may be essential to ovarian health.

In the Shadows of the Ovary

The horseshoe-shaped rete ovarii sits near the base of the ovary, where blood vessels and nerves enter. Despite its presence in many mammals—cows, cats, monkeys, dogs—it has remained virtually ignored in biology textbooks.

Jennifer McKey, a developmental biologist formerly at Duke University, noticed the peculiar curved shape while imaging mouse ovaries. She traced it through forgotten anatomical literature and matched it to the rete ovarii, kickstarting a new wave of investigation.

Her team found that the rete ovarii in mice is not a uniform blob of tissue—it contains three distinct regions: the intraovarian rete (IOR), embedded inside the ovary; the extraovarian rete (EOR), a maze of tubules ending in a bulb; and a transition zone known as the connecting rete (CR).

Using fluorescent dyes and protein-tracking techniques, the researchers found that fluids move directionally through the EOR and into the ovary. These fluids carry thousands of proteins, some known to influence egg development.

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

The Ovary’s “Antenna”?

Among these proteins, one stood out: IGFBP2, which can regulate insulin-like growth factors linked to egg follicle formation. This suggests the rete ovarii communicates directly with the ovary.

And it listens, too. Genetic tests revealed that cells in the rete ovarii turn on genes for hormone receptors—including those for estrogen and progesterone—at key times in the reproductive cycle.

Anbarci and her colleagues propose that the rete acts like an antenna, “tuning in” to hormonal and neurological cues from the body and responding by releasing targeted proteins into the ovary. Even neurons appear to contact the muscle tissue surrounding the rete, possibly triggering contractions that pump fluid into the ovary.

“It appears that the rete ovarii may have a role in ovarian homeostasis—maintaining the ovaries and their environment,” Adam Taylor, an anatomy professor at Lancaster University who was not involved in the study, told Live Science. “Finally and most interestingly is the potential endocrine [hormonal] role that the rete ovarii may have.”

If the Female Reproductive System Wasn’t Complicated Enough…

Despite these discoveries, many questions remain. Could shutting down the rete impair fertility? Does the human version behave the same way? So far, the research has been limited to mice. However, the biological similarities between early mouse and human sex-organ development make the findings compelling.

“This is just the beginning of the story,” said Serge Nef, a developmental biologist at the University of Geneva. “Whatever it is, is it important for ovarian function?”

The implications go beyond anatomy. Conditions like polycystic ovary syndrome, infertility, and premature ovarian failure often remain medically opaque. A deeper understanding of overlooked structures like the rete ovarii could open new therapeutic doors.

“The endocrine system plays a key role in gynecological health,” Taylor noted. “A greater understanding of any structures in this region has the potential to open up new therapeutic avenues and opportunities in treating various conditions.”

For now, the rete ovarii is no longer a forgotten footnote.