LIVER AND ADIPOSE TISSUES OF MICE CONCEIVED BY IN VITRO FERTILIZATION (IVF) SHOW INCREASED OXIDATIVE DAMAGE

Some human and animal studies indicate that adult offspring conceived by IVF show a predisposition to glucose intolerance and hypertension. At present, there is not a molecular mechanism that can explain these findings. Since oxidative stress has been linked to diabetes and hypertension and since IVF generated embryos are known to be exposed to high levels of reactive oxygen species (ROS), this study was performed to understand if oxidative damage is present in liver and adipose tissue of mouse offspring generated by IVF. Experimental animal study. CF1 x B6D2F1 mice were generated by IVF using potassium-enriched simplex optimized medium (KSOM) medium and 5% O2. Blastocysts generated by natural mating (flushed blastocysts = FB group) and transferred to recipients were used as control. IVF, embryo culture and embryo transfer at the blastocyst stage were performed as routinely done in the lab. At 40 weeks of life, mice were sacrificed, liver and gonadal adipose tissue harvested, frozen and stored at -80 Celsius. Tissues were assessed for glutathione (GSH) levels and oxidative damage in DNA (by measuring 8-hydroxy-deoxyguanosine- 8-OHdG) and proteins (carbonyl-group) using available kits. Lipids (F2α isoprostane) oxidative damage was assessed by mass spectrometry. Parametric statistics and p value < 0.05 was considered significant. Tabled 1IVF (n=11)FB (n=10)p value8-OH-dG liver (ng/ml)11.1810.610.048-OH-dG fat (ng/ml)11.0710.40NSF2α-isoprostane liver (ng/ml)18.9714.210.08F2α-isoprostane fat (ng/ml)8.874.520.04Carbonyl liver (nmol/mg)1.161.820.07Carbonyl fat (nmol/mg)2.121.85NSGlutathione liver (μM)0.080.05NSGlutathione fat (μM)0.020.010.01NS = Not Significant Open table in a new tab NS = Not Significant Liver and adipose tissue of IVF-generated offspring show biochemical evidence of persistent oxidative damage and altered antioxidant levels. These results might suggest a link between oxidative stress and the metabolic dysfunction found in IVF mice. Further studies are needed to understand the mechanism(s) leading to increase in oxidative stress and to discover strategies to mitigate these differences.