2023-10-17 14:23:13
The decline in fertility in older mice has been reversed by giving the animals a compound that is already found in most living cells. The process has also made the litters larger. The findings, published in the journal Nature Aging, offer clues that could help development of treatments for women with fertility problems.
The chances of getting pregnant, naturally or with assistive technology such as in vitro fertilization (IVF), decrease with age. This is due to the reproductive cells in the ovaries called oocyteswhich deteriorate and decrease in number throughout life.
It has been shown that a molecule called spermidinefirst isolated from sperm but now known to have functions in many cell types, extends the lifespan of yeast, flies, worms, and human immune cells.
Increased dietary intake of spermidine has also been linked to reduction of age-related problems in laboratory animals, including cardiovascular disease in mice and cognitive impairment in fruit flies. But the effects of it on oocyte aging were not clear.
The latest study uncovers the molecule’s potential to address major obstacles in reproductive medicine, Alex Polyakov, a fertility specialist at the University of Melbourne in Australia, tells Nature. “This research is undeniably innovative.”
young and old
For the study, Bo Xiong, a reproductive biologist at Nanjing Agricultural University in China, and his colleagues compared ovarian tissue samples from young and middle-aged mice and found that older mice they had much less spermidine in their ovaries. The older mice also had poorer quality oocytes and more degenerated follicles, structures in the ovaries that contain oocytes and release them during ovulation.
To explore whether these observations were related, the researchers injected some of the older mice with spermidine and compared their oocytes with those of control mice. Oocytes in spermidine-enhanced mice They developed more quickly and had fewer defects than those of untreated aged mice.
The mice that received the supplement also they had more follicles, a measurement often used in humans to estimate the quantity and quality of oocytes. This suggested that spermidine slowed the degeneration of follicles with age. Even when the researchers administered spermidine in drinking water rather than by injection, it still reversed the signs of oocyte aging.
Improved success rate in embryo formation
Spermidine booster also improved the success rate of sperm formation. blastocistos, the fertilized balls of dividing cells that become embryos. And older mice that received the compound and then conceived naturally produced about twice as many offspring per litter as older control mice.
Next, Xiong and his team investigated the mechanism behind spermidine’s effects. Observing that oocytes from untreated mice did not eliminate damaged mitochondria (the energy-producing components in cells) as efficiently as younger oocytes did, they sequenced the cells’ RNA. They found that genes related to cellular energy production and processes that clean up cellular waste had different expression patterns in young mice, older mice, and older mice that had received spermidine.
In mice enriched with spermidine, oocytes regained their ability to eliminate broken components. The compound also appeared to improve the function of healthy mitochondria in aged mice. The effect was similar in pig oocytes aged in a laboratory dish that were subjected to stress, suggesting that spermidine’s mechanism of action could be consistent across species. “Although we knew about spermidine’s anti-aging properties, we were still surprised by its remarkable effects,” says Xiong.
Cell cleaning
When researchers treated lab-cultured oocytes with a molecule that inhibits the mitochondrial cleanup process, they found that cells treated with spermidine matured much more slowly than those that were not treated with anything at all, further suggesting that the compound works with him cellular cleansing process to offer its anti-aging effects.
The results suggest that spermidine could be a promising fertility enhancer, says Xiaopeng Hu, a reproductive biologist at Shanghai Jiao Tong University in China. But before it reaches the clinics, researchers must investigate its safety, side effects and how different doses affect other processes in the body, such as cell and organ function, he says.
Jeremy Thompson, a reproductive biologist at the University of Adelaide in Australia, agrees. “The true test will be when we get to well-designed and conducted clinical trials.”
The next step for Xiong and his team is to test spermidine’s potential to improve fertility in human oocytes in the laboratory, investigating safe and effective doses. It is important to administer the correct dose, as the study also showed that excessive amounts of spermidine led to poorer quality oocytes in mice. “We need precise clinical trials to address these concerns before spermidine can be applied to increase fertility in humans,” she says.
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