In vitro fertilization exposure induced intergenerational effects on metabolic phenotype in mice

Research question What is the potential transmission of metabolic phenotype from in vitro fertilization (IVF) offspring to the subsequent generation? Design An IVF mouse model was established. The F1 generation mice were generated though IVF or natural mating and the F2 generation was obtained through the mating of F1 generation males with normal females. We examined their metabolic phenotype, including systemic and hepatic glucolipid metabolism. Results We found that IVF F1 males exhibited metabolic changes. Compared to the control group, IVF generations of F1 showed increased body weight, elevated fasting glucose and insulin, and increased serum triglyceride (TG). IVF F1 also increased expression of hepatic lipogenesis and autophagy genes. Moreover, IVF F1 males transmitted these metabolic changes to their own male progeny (IVF F2) in the absence of the dietary challenge. IVF F2 had increased periepididymal and subcutaneous fat and decreased insulin sensitivity. Under the "second hit" of a high-fat diet, IVF F2 further showed increased hepatic lipid deposition by unaltered autophagy levels. Conclusion Our research demonstrates the impact of IVF on hepatic glucose-lipid metabolism in two successive generations of offspring, highlighting the need for additional investigation. Enhanced comprehension of the mechanisms underlying the transmission of multigenerational effects induced by IVF could potentially lead to the advancement of therapeutic interventions for individuals experiencing infertility.