Multigenerational exposure to uranium changes morphometric parameters and global DNA methylation in rat sperm

Area of Science:

• Environmental toxicology
• Reproductive biology
• Epigenetics

Background:

• Environmental exposures during development can impact future generations' health.
• Previous studies showed uranium exposure caused subtle testicular defects.
• The multigenerational reproductive effects of uranium exposure were previously unexplored.

Purpose of the Study:

• To investigate the multigenerational reproductive effects of uranium exposure in rats.
• To assess impacts on sperm morphology and reproductive parameters across three generations.
• To explore epigenetic changes, specifically DNA methylation, in response to uranium exposure.

Main Methods:

• Rats (F0, F1, F2) were exposed to uranium (40 mg/L) during different life stages.
• Reproductive indices, epididymal weight, and sperm morphology were analyzed.
• Global DNA methylation profiles and mRNA expression of demethylation markers were assessed in spermatozoa.

Main Results:

• The F1 generation exhibited a reduced pregnancy rate.
• Sperm morphology was impaired in all exposed generations (F0, F1, F2), with the F1 generation showing the highest number of abnormal sperm.
• Global DNA hypomethylation was observed in the sperm DNA of the F2 generation.

Conclusions:

• Uranium exposure induces multigenerational sperm morphological defects and alters DNA methylation levels.
• Fetal exposure to uranium appears particularly detrimental to reproductive health.
• Further research is needed to confirm the epigenetic transgenerational inheritance of uranium-induced reproductive defects.