NUS Researchers Partly Restore Egg Maturation in Stiff, Aged-Like Ovarian Tissue
National University of Singapore researchers found that stiffer ovarian tissue cuts the links between eggs and their support cells, and that blocking the protein SMAD7 partly restored egg maturation in lab-grown follicles from preclinical models.
Researchers at the National University of Singapore have shown how stiffening ovarian tissue, which happens with age, disrupts egg development, and partly reversed the effect in the lab by targeting a signaling pathway, according to the university. The study was published in Aging Cell.
The tissue around eggs becomes 2.5 times stiffer with age
Comparing ovaries from young and aged preclinical models, the team found the supporting tissue became about 2.5 times as stiff with age, linked to a build-up of collagen. When follicles from young models were grown in gels mimicking aged tissue, the share of eggs reaching maturity was about a third of that in softer gels.
Support cells normally reach the egg through slender projections that pass nutrients and signals. In stiff gels there were about 28% fewer of these connections, and the cells made more of a protein called SMAD7, which acts as a brake on the signaling that builds them.
“The encouraging finding is that egg development improved even while the surrounding environment remained stiff.” — Professor Rong Li, Director, Mechanobiology Institute, National University of Singapore
A drug that lowers SMAD7 helped rebuild the links
Treating cultured follicles with mongersen, a drug that reduces SMAD7 production, reactivated the pathway, restored the connections, improved egg maturation and helped the eggs’ energy-producing mitochondria. The effect was only partial, which suggests other mechanisms are also involved.
The work was done on tissue from preclinical models in the lab, not in people. The team, led by Assistant Professor Jennifer Young and Professor Li, next plans to test the approach in follicles from older models. The paper is in Aging Cell.
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