What makes a woman’s biological clock tick?

Natural fertility in women fluctuates between highs and lows in the shape of an inverse U-curve in part due to naturally occurring chromosome errors in human eggs, according to new research published in Science.

To understand exactly what this means, we first need to take a look at basic reproductive biology. Unlike boys who begin forming sperm only after they hit puberty, girls are born with the exact set of eggs that they will carry through life. These eggs remain immature until their carrier has a menstrual cycle.

“While the eggs lie dormant, a kind of molecular glue will make the chromosomes stick together. Later, when the eggs are maturing, the chromosomes divide. But the older the women become, the greater the risk that the glue will break down prematurely,” said lead researcher Eva Hoffmann of the University of Copenhagen, in a statement.

In an examination of 3,000 eggs from girls and women between the ages of nine and 43, researchers at the University of Copenhagen found that the eggs of teenage girls and women in their mid-30s and older both experience chromosomal errors, or aneuploidy, that “result in genomic imbalance and pregnancy loss.” In both cases, these chromosomal errors increase the likelihood that eggs will be expelled without fertilization. It acts as a “molecular clock” of sorts, ensuring that only the finest eggs get fertilized.

“We have known for a long time that we humans have a unique fertility curve compared to many other species. The curve starts out very poorly in the teenage years and starts to go downhill again when women reach their 30s. But until now, we have not known what is actually causing these changes,” said Hoffmann.

When teens mature into women in their 20s, their eggs become healthier as chromosome errors disappear. But as the hereditary material contained in the “glue” begins to break down, chromosome errors occur that may lead to Down Syndrome in infants or infertility in older women.

Researchers are unclear as to why fertility follows this cycle, but Hoffman has two working theories. On one side of the age spectrum, it could prevent young women from becoming pregnant before their bodies are fully developed with, for example, wider hips for childbirth. On the other hand, it could lend to the “grandmother hypothesis”, whereby females lose the ability to reproduce so that they can take on a supportive role for other women and children in their family or social circle.

Hoffman concludes that understanding how women’s fertility works can help to inform how physicians counsel for and treat infertility.

“Pregnancy loss is still a taboo, but with knowledge like this, we are able to better understand and demonstrate that it is a natural thing. At the same time, a greater understanding of the mechanisms behind our biological clock may enable us to better control the breakdown of the eggs,” concludes Hoffmann.