Women have been told for years that if they don't have children before their mid-30s, they may not be able to. But a new study has identified a drug that extends egg viability in worms, even when taken midway through the fertile window, which could theoretically extend women's fertility by three to six years. The work appears in the journal Current Biology.

"One of the most important characteristics of aging is the loss of reproductive ability in mid-adulthood," said the senior author. "As early as the mid-30s, women start to experience declines in fertility, increased rates of miscarriage and maternal age-related birth defects. All of these problems are thought to be caused by declining egg quality, rather than a lack of eggs."

Worms have many of the same genes as humans, including those that drive the aging processes of their three-week-long lives. Several years ago, researchers in the lab discovered that C. elegans not only exhibits a similar mid-life decline in reproduction, but also that their unfertilized eggs (oocytes) showed similar declines in quality with age to human eggs.

As they investigated why, the researchers focused on the genes and proteins that are more common in healthy, young eggs than aging ones. They recently decided to try the opposite approach -- investigate why some proteins are "downregulated," or less common, in the lower-quality oocytes.

One downregulated group of proteins, cathepsin B proteases, that are rare in high-quality eggs and more common in eggs that have begun degrading with age. The existence of drugs that block these exact proteins provided an opportunity to test their effects. When the drug was administered the treated worms still had healthy eggs long after the control group did not.

They had administered the drug at the beginning of the worms' reproductive window, the equivalent of puberty, so even though the drug worked, it wouldn't be helpful to adult women, senior author said.

"What you want is a drug [that] you could give to a woman in her mid-30s, and it would still preserve the oocytes that she has," senior author said. When the drug was administered halfway through the worms' reproductive period it worked beautifully.

The results were better than they had hoped, showing that even a late administration of the drug could extend the worms' egg quality. Another experiment that knocked out the cathepsin B genes entirely succeeded in extending worms' fertility by about 10 percent. If applied to humans, author  said, "It could be a three- to six-year extension of your reproductive period."

The cathepsin B inhibitor is nowhere near ready for testing in humans yet, senior author said. "That's not our area,"  she said. "We wanted to say: This is something that could work. ... The idea that you could do something mid-reproduction to improve the rest of reproduction -- for me, that's a game changer."

https://www.princeton.edu/news/2018/02/22/fertility-breakthrough-new-research-could-extend-egg-health-age

http://www.cell.com/current-biology/abstract/S0960-9822(18)30085-X