Oral Presentation ESA-SRB-NZSE-CaSR 2026 in conjunction with ENSA

SIRT1 overexpression mitigates oxidative stress in in vitro aged oocytes and improves IVF embryo quality (143997)

Georgia A Bennett 1 , Shannon P Smyth 1 , Alexandra J Harvey 1 2 , David K Gardner 1 2 , Elizabeth G Bromfield 1 3 4
  1. School of BioSciences, The University of Melbourne, Melbourne, VIC, Australia
  2. Melbourne IVF, Melbourne, VIC, Australia
  3. Centre for Reproductive Science, University of Newcastle, Newcastle, NSW, Australia
  4. Infertility and Reproduction Research Program, Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia

1. Background: 

The success of assisted reproduction is negatively correlated with increased age and oxidative stress (OS). Sirtuins are a class of NAD+-dependent deacetylases implicated in regulating oocyte quality, overall longevity, and OS. This study aimed to determine whether Sirt1 overexpression could protect oocytes and embryos against in vitro aging and OS. We hypothesised that increased SIRT1 would confer resilience to OS and improve IVF embryo quality.

 

2. Methods: 

To evaluate the impact of Sirt1 overexpression, a global Sirt1super mouse model was used. Oocytes were collected from 4–7-week-old transgenic and wildtype mice following superovulation. Reactive oxygen species (ROS) production in fresh and 8h in vitro aged oocytes was analysed using H2DCFDA (n=5 replicates). IVF was conducted with Sirt1super or wildtype oocytes and embryos were cultured for 4.5 days. Embryo quality was analysed using H2DCFDA in untreated and H2O2 (25µM) treated 8-cell/morula embryos (n=5 replicates). Blastocyst cell allocation was assessed using differential nuclear staining (n=5 replicates) with developmental timing measured using an EmbryoScope (n=5 replicates).

 

3. Results: 

In oocytes, Sirt1 overexpression protected against in vitro aging by decreasing ROS production (p=0.03). Decreased sensitivity to a H2O2 challenge was also observed for Sirt1super embryos, suggesting that SIRT1 may confer protection against exogenous ROS. Blastocysts derived from Sirt1super females had significantly more cells in their trophectoderm (p=0.01) and an increased total cell number (p=0.007). Morphokinetic analysis revealed that embryos derived from Sirt1super oocytes exhibited faster developmental timing to expanded (p=0.03) and hatching blastocyst stages (p<0.0001). Embryos from Sirt1super females also had an increased rate of blastocyst expansion (p=0.02).

 

4. Conclusion: 

These data suggest that modulating SIRT1 concentrations in vivo may protect oocytes against in vitro aging and improve IVF embryo quality. Upon validation with pharmacological modulators, SIRT1 could be a promising target for improving oocyte and embryo quality in a clinical setting.