IVF exposure induced intergenerational effects on metabolic phenotype in mice

Area of Science:

• Reproductive biology
• Metabolic research
• Genetics

Background:

• Assisted reproductive technology (ART), including in vitro fertilization (IVF), is increasingly used globally.
• Potential long-term health consequences of ART on offspring are not fully understood.
• Investigating multigenerational effects of IVF on metabolic health is crucial.

Purpose of the Study:

• To examine the transmission of metabolic phenotype from IVF offspring to the subsequent generation.
• To assess the impact of IVF on systemic and hepatic glucolipid metabolism across generations.
• To explore the role of diet as a secondary factor in IVF-induced metabolic changes.

Main Methods:

• Establishment of an IVF mouse model.
• Generation of F1 and F2 offspring through IVF and natural mating.
• Analysis of metabolic phenotypes, including body weight, glucose, insulin, serum triglycerides, and hepatic gene expression (lipogenesis, autophagy).

Main Results:

• IVF F1 males exhibited increased body weight, fasting glucose and insulin, and serum triglycerides.
• Increased hepatic lipogenesis and autophagy gene expression were observed in IVF F1 mice.
• IVF F1 males transmitted metabolic changes to IVF F2 males, including increased fat deposition and decreased insulin sensitivity, even without dietary challenges.

Conclusions:

• IVF impacts hepatic glucose-lipid metabolism in successive generations of offspring.
• Multigenerational effects of IVF on metabolic health warrant further investigation.
• Understanding these mechanisms could inform therapeutic strategies for infertility and related metabolic disorders.