Restoring a deficient “motor” protein could improve fertility success

The leading cause of miscarriage is that human eggs are surprisingly bad at managing the number of chromosomes in them. But now, researchers at the Max Planck Institute have identified a motor protein that helps this process function smoothly, leading to a potential new way to improve the success rates of fertility treatments.

Humans usually inherit 46 chromosomes, with half being contributed from one parent’s sperm and the other half coming from the other parent’s egg cells. Egg precursor cells, called oocytes, contain two copies of each chromosome, and lose one of them through a cell division process. This is guided by the spindle apparatus, a structure of fibers that pull one copy of each chromosome towards opposite ends of the spindle, before the oocyte divides between them.

The problem is, errors are common during this process in humans. The majority of miscarriages are caused by a mature egg that contains too many or too few chromosomes, while conditions like Down syndrome can also arise from chromosomal abnormalities.

“We already know that human oocytes frequently assemble spindles with unstable poles,” said Melina Schuh, corresponding author of the study. “Such unstable spindles misarrange chromosomes during division.”

ImageJ=1.53j unit=micron

The spindle apparatus (green) separates the chromosome pairs (magenta) in a human oocyte

Chun So / Max Planck Institute for Multidisciplinary Sciences

Strangely enough, other mammals don’t seem to have this same error rate, so for the new study, the researchers investigated differences between them and us. They conducted a molecular inventory of the proteins that play a role in stabilizing the spindles, comparing human oocytes with those from mice, pigs and cows.

In doing so, the team identified a particular protein called KIFC1, which is relatively deficient in human oocytes but far more common in the other animals tested. This motor protein builds bridges between spindle fibers, keeping them stable. To test whether a lack of this protein was behind the high chromosomal error rate, the team removed it from mouse and cow oocytes.

“Without this motor protein, most mouse and bovine oocytes assembled unstable spindles like human oocytes and more chromosome segregation errors occurred,” said Chun So, first author of the study. “Thus, our results suggest that KIFC1 is critical in ensuring error-free distribution of chromosomes during meiosis.”

Next, the researchers checked if it also worked the other way. They added extra KIFC1 into human oocytes, and found that the spindles became significantly more stable, with fewer errors occurring. With further work, this find could be a breakthrough for improving the success rates of IVF or other fertility treatments.

“Introducing KIFC1 into human oocytes could thus be a possible approach to reduce defective eggs,” said Schuh. “This might help to make fertility treatments more successful.”

The research was published in the journal Science.

Source: Max Planck Institute

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