Prenatal Lipopolysaccharides Exposure Induces Transgenerational Inheritance of Hypertension

Area of Science:

• Environmental epigenetics
• Reproductive toxicology
• Cardiovascular disease research

Background:

• Adverse prenatal exposures can lead to offspring diseases like hypertension.
• The transgenerational transmission of hypertensive phenotypes is not well understood.

Purpose of the Study:

• To investigate the transgenerational effects of prenatal lipopolysaccharide (LPS) exposure on hypertension.
• To elucidate the epigenetic mechanisms underlying transgenerational hypertension.
• To explore potential preventative strategies targeting oxidative stress.

Main Methods:

• A rat model of prenatal LPS exposure was established.
• Blood pressure was monitored via telemetry and tail-cuff methods.
• Kidney transcriptome analysis (RNA sequencing) was performed on the third generation.
• Epigenetic modifications (H3K9me2, KDM3B) and gene expression (Rac1) were analyzed.
• The effects of tempol (ROS scavenger) and spironolactone were evaluated.

Main Results:

• Prenatal LPS exposure induced hypertension and salt sensitivity in offspring up to the fifth generation.
• Hypertensive offspring exhibited Rac1 gene upregulation and activated mineralocorticoid receptor signaling.
• LPS exposure led to oxidative stress, upregulating KDM3B in oocytes, causing heritable H3K9me2 reduction and Rac1 upregulation.
• Tempol treatment prevented hypertension in the first generation and its transgenerational inheritance.

Conclusions:

• Adverse prenatal exposure can induce transgenerational hypertension via epigenetic mechanisms.
• Targeting reactive oxygen species offers a potential strategy for preventing and treating transgenerational hypertension.