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Health and Medicinemedicine

Gene-Editing Technique Allows Infertile Mice To Have Babies

author

Ben Taub

Freelance Writer

clockMay 4 2022, 15:12 UTC
Mouse pups
Eight of 19 infertile mice gave birth. Image credit: Vadim Zakharishchev/Shutterstock.com

Mice born with a genetic defect that renders them infertile have given birth to litters of pups thanks to a gene-editing technique. Describing this incredible breakthrough in the journal Cell Reports Medicine, the researchers behind the experiment say that their approach could one day be used to treat infertility in humans.

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Premature ovarian insufficiency, which occurs when ovaries become incapable of releasing the hormones needed for the production of eggs, is thought to affect around 1 percent of women by the age of 40. The condition is dependent upon numerous molecules that regulate the crosstalk between oocytes and granulosa cells, which produce estrogen, progesterone, and other key hormones.

One such molecule, known as KITL, controls numerous stages of oocyte development, which is why individuals harboring mutations within the gene that codes for this particular compound tend to suffer from fertility issues. Unfortunately, it is not possible to directly treat patients with KITL, as the impermeability of the blood-follicle barrier prevents uptake by the ovaries.

The study authors, therefore, used a type of virus called an adeno-associated virus (AAV) to introduce a gene for the production of KITL into female mice that lacked this key reproductive molecule. Considered to be the most promising viral vectors for gene therapy, AAVs are able to deliver macromolecules into cells via a process called transcytosis.

While the researchers hoped to see an increase in KITL production within these infertile mice, they were somewhat stunned to find that the rodents actually became capable of reproduction following treatment. Of the 19 mice involved in the experiment, eight produced pups after mating with a male, with one mother going on to get pregnant again and deliver a second litter.

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“Fertility restoration by natural mating was unexpected,” write the study authors.

Importantly, all offspring were completely normal and healthy, and none of the viral DNA was found in the pups. According to the researchers, “the lack of transgene DNA in the offspring following direct ovarian injection suggests that AAV injection may be safe.”

“Despite the success of this work, efforts to increase the transduction efficiency and fertility are still needed,” they say. “More than half of the injected mice remained infertile, and only one of the fertile mice could produce two litters.”

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Long-term fertility tests will help to confirm the safety and efficacy of the approach, yet the authors are understandably enthusiastic about the implications of their findings to date. Overall, they conclude that “our results, although in mice, suggest that some cases of female infertility in humans may be treated by AAV-mediated gene therapy.”


Health and Medicinemedicine
  • medicine,

  • fertility

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