Researchers reverse the reproductive clock in mice.


It is known that the quality of a woman’s eggs is directly related to her ability to have a baby and her level of fertility. A woman’s egg quality can be translated to the percentage of her total number of eggs that contain normal chromosomes, with high-quality eggs possessing the best chance of a successful pregnancy. However, the decline in egg quality is a natural, inevitable result of age, which significantly deteriorates from late in the third decade of life onwards in humans. Therefore, viable strategies to either preserve or rejuvenate oocyte quality during aging is highly desirable. Now, a study from researchers at the University of Queensland improves fertility rates in older female mice via oral doses of a metabolic compound that reverses the aging process in eggs. The team states their findings suggest there is an opportunity to restore egg quality and female reproductive function with the oral administration of nicotinamide adenine dinucleotide (NAD) precursors orally. The opensource study is published in the journal Cell Reports.

Previous studies show the enzyme-substrate NAD is a cofactor, meaning it can be found in two forms in redox reactions, carrying and donating electrons in important metabolic reactions in the body. These essential reactions provide energy for metabolism, DNA repair, and epigenetic homeostasis. Unfortunately, levels of NAD decline with age in somatic tissues, with the reversal of this decline using precursors for NAD gaining momentum as a treatment. The current study investigates whether the reproductive aging process can be reversed by an oral dose of nicotinamide mononucleotide (NMN), the precursor compound used by cells to create NAD.

The current study utilizes mice between the ages of 12 and 14 months-old due to the fact their fertility starts to decline around 8 months of age as their oocyte defects are similar to those in humans. Results using hyperspectral microscopy show that NAD levels had declined in oocytes from the aged animals, compared with young animals aged 4- to 5-weeks-old. Data findings show that egg quality is dramatically restored in the older mice given low doses of NMN in their drinking water for four weeks, causing an increase in live births during the trial.

The lab stresses that a decline was not observed in whole ovary NAD levels with age, suggesting the oocyte is particularly vulnerable to NAD depletion as opposed to the surrounding stroma which appears unaffected. They go on to add that it was shown NMN treatment increases NAD levels in the whole ovary of elderly mice, and conclude these findings suggest that restoration of NAD levels in older mice represents an opportunity to rescue female reproductive function in mammals.

The team surmises their data shows NAD levels in the oocytes of aged mice decline with age, which was replenished by NMN to restore oocyte quality, enhanced ovulation rate, and fertility. For the future, the researchers urge caution stating that although their data holds great potential, clinical trials are a long way off.

Source: University of Queensland

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