Perinatal testosterone exposure potentiates vascular dysfunction by ERβ suppression in endothelial progenitor cells

Area of Science:

• Endocrinology
• Vascular Biology
• Epigenetics

Background:

• Excessive androgens may harm the vascular system.
• The effects of prenatal testosterone on offspring vascular function are unknown.
• Testosterone therapy is linked to cardiovascular issues in men.

Purpose of the Study:

• To investigate the mechanism by which perinatal testosterone exposure affects vascular function in offspring.
• To explore the role of estrogen receptor β (ERβ) in testosterone-induced vascular dysfunction.

Main Methods:

• Perinatal testosterone exposure in mice.
• Analysis of estrogen receptor β (ERβ) expression in endothelial progenitor cells (EPCs) and mouse endothelial cells (MECs).
• Epigenetic analysis, including DNA methylation.
• Bone marrow transplantation experiments.

Main Results:

• Perinatal testosterone exposure suppressed ERβ in offspring EPCs via epigenetic changes.
• ERβ suppression led to mitochondrial and fatty acid metabolism dysfunction, increasing reactive oxygen species (ROS) and DNA damage.
• Restoring ERβ or SIRT1 function ameliorated vascular dysfunction.

Conclusions:

• Perinatal testosterone exposure potentiates vascular dysfunction in offspring.
• Estrogen receptor β (ERβ) suppression in EPCs is a key mechanism.
• Epigenetic modifications play a crucial role in mediating these effects.