Scientists at the University of Adelaide, Monash University and the Baker IDI Heart and Diabetes Institute, Melbourne, were able to increase the fertility of obese mice by reverting some of the obesity-induced changes in their eggs. This work suggests that therapeutic approaches could be developed in the future to help overweight women to conceive. The research has just been published in the scientific journal Development.
Obese women often require access to fertility treatments. Previous studies have shown that this difficulty to conceive is partially due to damage to their eggs. The machinery responsible for folding proteins in the cell is particularly affected by overnutrition, giving rise to a variety of downstream effects. The team led by Rebecca Robker from The University of Adelaide reasoned that it might be possible to improve the viability of the eggs by inhibiting these downstream effects.
‘Research into how obesity affects other tissues, such as liver and brain, has revealed that a very specific stress response is often involved. We found that the egg cells of both obese mice and women are similarly affected by this stress response. Once we had identified the type of stress that was occurring we used agents known to alleviate it. We were particularly interested in one that was already being trialled in humans to address stress responses in diabetes’, said Dr Robker.
The team injected obese mice with compounds that can inhibit the molecular pathways involved in the damage. Eggs were then removed from the obese mice, fertilised and transplanted into surrogate mothers, resulting in a clear improvement in their ability to produce viable embryos. ‘Similar to what our colleagues in diabetes research had found in muscle, the new agents very potently alleviated the stress in eggs’, Dr Robker explained. ‘Because eggs provide the building blocks for making an embryo, reverting cellular damage in eggs not only prevents damage to that cell but prevents the damage from being perpetuated into the next generation.’
These results suggest that a similar strategy could be used in the future to help obese women to conceive, by therapeutically reducing the damage to their eggs. ‘More broadly, the work shows that maternal nutritional signals are contained within the eggs and are modifiable even in the days just prior to fertilisation. This is more key evidence for the importance of women having good nutrition and health before conceiving’, added Dr Robker.
Wu, L. L., Russell, D. L., Wong, S. L., Chen, M., Tsai, T., St John, J. C., Norman, R. J., Febbraio, M. A., Carroll, J. and Robker, R. L. (2015). Mitochondrial dysfunction in oocytes of obese mothers: transmission to offspring and reversal by pharmacological endoplasmic reticulum stress inhibitors . Development, 4, 681-691. Doi: 10.1242/dev.114850