Leading hypothesis for miscarriages, birth defects ruled out

Scientists have debunked the theory that eggs produced by women later in life have weaker connections between chromosomes which contributes to miscarriages and developmental abnormalities.
One of the leading thoughts on why older women have an increased risk of miscarriages and children with birth defects is the "production-line hypothesis".
It says the first eggs produced in a female's foetal stage tend to have better connections or "crossovers" between chromosomes.
The hypothesis asserts that as a woman ages eggs produced later will have more faulty chromosomes - leading to miscarriages and developmental abnormalities.
After counting the actual chromosome crossovers in thousands of eggs, Washington State University researchers found those of eggs produced early in the foetal stage were no different from those produced later.

"If the production-line hypothesis were true, you'd expect lots of abnormal cells and you would expect them all to be happening late," said Ross Rowsey, a doctoral candidate in WSU's Center for Reproductive Biology.

"We do see a pretty high incidence of abnormal cells, but they're just as likely to be happening early as late," Rowsey said.
Faulty chromosomes, in particular the incorrect number of chromosomes known as aneuploidy, account for more than one-third of human miscarriages and congenital birth defects, including Down syndrome. Their frequency rises dramatically in older women.
"The age of the woman is probably the most important risk factor associated with any human genetic disease," said Terry Hassold, a WSU professor of reproductive biology and co-author with Rowsey and others of a paper on their findings in the American Journal of Human Genetics.

"It's an extraordinary complication to human reproduction," he said.
"By the time a woman is in her 40s, it's likely the majority of her eggs don't have the right number of chromosomes. And if you don't have the right number of chromosomes, you'll either have a miscarriage or a congenital disability," he said.
The production-line hypothesis was put forth in 1968 by Alan Henderson and Robert Edwards, winner of the Nobel Prize for development of in-vitro fertilisation. It has since become one of the most cited explanations for human aneuploidy.
To test the hypothesis, Rowsey looked at more than 8,000 eggs from 191 second-trimester foetal ovaries. The material came from elective abortions in accordance with the guidelines of the National Institutes of Health in US.

Rowsey treated eggs so proteins at chromosome crossovers would fluoresce, making dozens of glowing dots visible under a microscope. He then counted them and analysed their distribution.
The results showed a lot of variation within women and between women but no relationship to a woman's age.