Family Matters

Why It’s Harder For Older Women to Have Healthy Babies

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No one likes being labeled, but celebrate your 35th birthday and get pregnant and you’re out of luck: like it or not, the letters “AMA” get slapped across your chart. AMA, or advanced medical age, is largely an arbitrary designation. After all, it’s not as if your eggs are aware it’s your big day. But experts need a way to delineate the increasing risks inherent in conceiving a child after you’ve passed the 35-year mark.

As women reach their mid- to late-30s and hit 40, they are at greater risk of having chromosomal problems in their eggs — known in scientific terms as maternal age–associated aneuploidy. As a result, all the cells that result from the abnormal chromosomes will also be irregular. (More on A New Artificial Ovary May Someday Boost Women’s Success with In Vitro)

Most of the time, the situation turns lethal because an affected embryo will die shortly after. Down syndrome, or Trisomy 21, is a notable exception; it’s one of the only aneuploidies that can result in a live birth. “By age 40, probably half of the eggs are aneuploidies,” says Michael Lampson, an assistant professor of biology at Penn who has co-authored research into the mechanism behind the abnormalities.

Now Lampson and Richard Schultz, a biology professor at Penn, have finally figured out what’s behind all the abnormal chromosomes. They used mice to show that aneuploidy is probably a result of poor chromosome cohesion. What’s that? Well, first a mini-science lesson: When chromosomes replicate, they have to be held together. Molecules called cohesins do that job, allowing chromosomes to pair off correctly. Imagine two sticks as the chromosomes, and a rubber band binding them together as the cohesin. In normal cell division, one stick goes to one cell and one stick goes to another. But aneuploidy upends the normal path of cell division.

In a recent issue of Current Biology, Lampson and Schultz concluded that the increase in chromosomal disorders experienced by older women is largely related to a decrease in cohesin proteins, which diminish as a part of the aging process. Chromosomes in older eggs simply don’t have enough of this protein, and that causes the chromosomes to do some unscripted acrobatics: Rather than heading off in the right direction toward two separate cells, they might both wind up attaching to one cell or another. It’s during this delicate period that mistakes can result in chromosomal disorders, including Down syndrome. The projection that half of 40-year-old women’s eggs have chromosomal problems? It’s probably a significant underestimate, since most aneuploidies abort early in pregnancy. “Most of the time, those bad eggs are really bad,” says Schultz. “They don’t give rise to a child.” (More on Why Most Moms Don’t Follow Breast-Feeding Recommendations)

While the research goes a long way toward explaining why older women have a tougher time delivering a healthy baby, it doesn’t offer any solutions. “We can’t come in with a magic bullet and make it better,” says Schultz. “The biological clock goes tick-tock once you start hitting 35. That’s why it’s easier for younger women to have children.”

One possibility might be to reload the eggs with cohesin. The protein is added to the chromosomes in egg cells when a baby girl is still in utero. “That cohesin has to last for 40 years or so, which is why it’s so susceptible,” says Lampson. Even if it would be possible to inject cohesin into eggs, it’s likely that older eggs wouldn’t welcome the infusion. “It’s one of the things we’re thinking about,” says Lampson, “but we don’t know exactly what to do.”

Still, it’s a start, notes Schultz. “To fix something, you first need to know what’s broken,” he says.

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