Multigenerational Exposure to Uranium Changes Sperm Metabolome in Rats

Area of Science:

• Environmental toxicology
• Reproductive biology
• Metabolomics

Background:

• Male infertility is a significant public health concern.
• Environmental factors, including uranium exposure, can negatively affect male reproduction.
• Multigenerational studies are crucial for understanding long-term reproductive health impacts.

Purpose of the Study:

• To investigate the multigenerational effects of uranium exposure on male rat reproduction.
• To identify metabolic changes in sperm following uranium exposure across generations.
• To assess the utility of metabolomics in detecting uranium's reproductive toxicity.

Main Methods:

• Multigenerational exposure of rats to uranium (F0, F1, F2 generations).
• Mass spectrometry-based metabolomic analysis of epididymal spermatozoa.
• Statistical analyses including Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA).

Main Results:

• Significant uranium content detected in the F0 generation.
• A reduction in pregnancy rates observed in the F1 generation.
• Distinct metabolic profiles identified between generations using PCA and PLS-DA.
• Parental uranium exposure demonstrated metabolic effects on spermatozoa in subsequent generations.

Conclusions:

• Parental uranium exposure has transgenerational metabolic consequences on male reproductive health.
• Metabolomics of spermatozoa is a promising approach for assessing multigenerational toxic effects.
• This study provides a foundation for identifying biomarkers of uranium-induced male infertility.