Transplanted ovaries appear to take on the age of their recipients’ bodies. When young mice received ovaries from animals that were past their natural fertility window, the young mice gave birth to healthy offspring. This suggests the younger bodies lowered the molecular age of the older ovaries. Transplanting younger ovaries into older mice also boosted the animals’ overall health, adding to the evidence that ovaries play a greater role in ageing and physiology than we realised.
“Young ovaries lowered the biological age of the brain, liver and uterus in old recipient mice,” says Sharif Iqbal at Harvard Medical School. The discovery follows recent research that found transplanted hearts shift towards the recipient’s age. “An organ’s biological age is not fixed at the time it is transplanted,” says Iqbal. “It responds to the body it lives in. Old hearts became younger in young recipients and old ovaries became molecularly younger in young mice.”
Iqbal and his colleagues used mice of different ages to build an “ovarian clock”, based on levels of gene expression and DNA changes that occur with age.
They then surgically transplanted ovaries between young mice (about 4 months old) and older mice (about 13 months old), which are generally infertile. This gave four combinations: young ovaries in young mice, older ovaries in young mice, young ovaries in older mice and older ovaries in older mice.
Four to five months later, the researchers found that the older ovaries placed in younger mice became molecularly younger, while the younger ovaries in older mice became older. They also observed that being in an older body increased inflammation in the younger ovaries, while a younger body reduced it in the older ovaries.
When the mice mated, four to five months after the transplant, the younger mice with older ovaries gave birth to healthy offspring, says Iqbal. Older ovaries transplanted into different older mice produced no births, he says.
The researchers also found evidence that the age of ovaries impacts the rest of the body. “In a younger body, aged ovaries showed gene and pathway level changes that resemble those caused by treatments known to extend lifespan in mice, such as calorie restriction and the drug rapamycin,” says Iqbal.
Other researchers recently found that ovaries don’t sit inert in the body after menopause, but have an identity shift that may contribute to inflammation. “The ovary is not just a passive reproductive organ. It can influence how other organs age,” says Iqbal.
The researchers hope that understanding which molecular signals made the older ovaries work in the younger mice could lead to treatments that support egg quality and ovarian function in women for longer. Ovary transplants can be carried out due to early menopause or a loss of ovarian reserve following medical treatments like chemotherapy. “If we can identify the signals responsible, it may be possible to mimic a younger environment with treatments [and] without transplantation,” says Iqbal.
Francesca Duncan at Northwestern University in Chicago says the results reveal how plastic ovaries are. “Older ovaries [are] influenced by a young environment and vice versa,” she says. “These results provide important support for therapeutic interventions to extend ovarian longevity.” However, ovarian plasticity can probably only be stretched so far, she says.