Mice generated by in vitro fertilization exhibit vascular dysfunction and shortened life span

Area of Science:

• Reproductive Medicine
• Vascular Biology
• Epigenetics

Background:

• Children conceived via assisted reproductive technologies (ART) show vascular dysfunction similar to those with maternal preeclampsia.
• Long-term effects of ART-associated vascular issues in healthy children are not well understood.

Purpose of the Study:

• To investigate the vascular and epigenetic consequences of ART in a mouse model.
• To explore the potential role of epigenetic modifications in ART-associated vascular dysfunction.
• To assess the impact of ART on lifespan, particularly under dietary challenges.

Main Methods:

• Generated ART mice and assessed their vascular function (endothelial dysfunction, stiffness, blood pressure).
• Analyzed epigenetic modifications, specifically DNA methylation at the eNOS gene promoter in ART mice aortas.
• Administered a deacetylase inhibitor to ART mice and evaluated effects on vascular function and offspring.
• Challenged ART mice with a high-fat diet to assess lifespan.

Main Results:

• ART mice exhibited endothelial dysfunction, increased arterial stiffness, and hypertension.
• Vascular dysfunction was observed in progeny of male ART mice, indicating transgenerational epigenetic effects.
• ART mice showed altered methylation of the eNOS gene promoter, correlating with reduced eNOS expression and nitric oxide (NO) synthesis.
• Deacetylase inhibitor treatment normalized vascular methylation and function, preventing dysfunction in offspring.
• ART mice on a high-fat diet had a 25% shorter lifespan compared to controls.

Conclusions:

• ART can induce significant vascular dysfunction and hypertension in mice, potentially through epigenetic alterations in genes like eNOS.
• These ART-associated vascular and epigenetic changes may originate from the embryo's environment, possibly influenced by hormonal stimulation during ovulation.
• Interventions targeting epigenetic modifications, such as deacetylase inhibitors, can potentially reverse ART-induced vascular problems.
• ART may shorten lifespan, especially when combined with adverse dietary factors like a high-fat diet.