A new study has found a link between genetic mutations in the NEMP family and early menopause. The study appears in Science Advances.
The team from Washington University School of Medicine in St. Louis, found that when the NEMP1 gene—nuclear envelope membrane protein 1—is missing in fruit flies, roundworms, zebrafish, and mice, the animals lose their fertility unusually early but appear otherwise healthy. When analyzing genetic data in people, researchers also identified an association between mutations in this gene and early menopause.
In animals, mutations in the equivalent gene had been previously linked to impaired eye development in frogs. Interestingly, the team was originally hoping to find genes involved with eye development in the early embryos of fruit flies.
"We blocked some gene expression in fruit flies but found that their eyes were fine," said senior author Helen McNeill. "So, we started trying to figure out what other problems these animals might have. They appeared healthy, but to our surprise, it turned out they were completely sterile. We found they had substantially defective reproductive organs."
In females, the researchers found that the envelope that contains the egg's nucleus was shaped abnormally. To study the shape of the nuclear envelope, they used atomic force microscopy to poke a needle into the cells, first penetrating the outer membrane and then the nucleus's membrane.
The team’s goal is to continue investigating whether women with fertility problems have mutations in NEMP1. To help establish whether such a link is causal, they have developed human embryonic stem cells that, using CRISPR gene-editing technology, were given specific mutations in NEMP1 listed in genetic databases as associated with infertility.
"We know there are variants in this gene associated with early menopause. And when we studied this defect in mice, we see that their ovaries have lost the pool of egg cells that they're born with, which determines fertility over the lifespan,” McNeill adds. “So, this finding provides a potential explanation for why women with mutations in this gene might have early menopause. When you lose your stock of eggs, you go into menopause."