Genetic mutations may be linked to infertility, early menopause
A new study from Washington University School of Medicine in St. Louis (WUSTL) identifies a specific gene’s previously unknown role in fertility, according to a press release from the university. When the gene is missing in fruit flies, roundworms, zebrafish and mice, the animals are infertile or lose their fertility unusually early but appear otherwise healthy. Analyzing genetic data in people, the researchers found an association between mutations in this gene and early menopause. The study appears in the journal Science Advances.
The human gene — called nuclear envelope membrane protein 1 (NEMP1) — is not widely studied. In animals, mutations in the equivalent gene had been linked to impaired eye development in frogs. The researchers who made the new discovery were not trying to study fertility at all. Rather, they were using genetic techniques to find genes involved with eye development in the early embryos of fruit flies.
Though it varied a bit by species, males and females both had fertility problems when missing this gene. And in females, the researchers found that the envelope that contains the egg’s nucleus — the vital compartment that holds half of an organism’s chromosomes — looked like a floppy balloon.
To study this floppy balloon-like nuclear envelope, the researchers used a technique called atomic force microscopy to poke a needle into the cells, first penetrating the outer membrane and then the nucleus’s membrane. The amount of force required to penetrate the membranes gives scientists a measure of their stiffness. While the outer membrane was of normal stiffness, the nucleus’s membrane was much softer.
The researchers would like to investigate 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.
