Multigenerational effects of uranium exposure reveal stronger testicular dysregulation in the second generation

Infertility is a significant public health issue that can be influenced by environmental pollutants. As a radioactive heavy metal and environmental contaminant, uranium has the potential to impact fertility.

This study assesses the multigenerational reproductive effects of chronic, non-nephrotoxic uranium exposure across three generations of male rats.

In this study, a non-nephrotoxic uranium solution (40 mg/L) was chronically administered via drinking water to male and female F0 rats (n = 20 per group) throughout their lifespan. The objective was to evaluate the potential reprotoxic effects of uranium on males across three generations (F0, F1, F2), with a focus on spermatogenesis, steroidogenesis, and testicular homeostasis, including oxidative stress, inflammation, apoptosis, and vitamin D metabolism.

Steroidogenesis was modulated in all generation, with dysregulation of sex and pituitary hormones (testosterone, estradiol, gonadotropins, Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH). Morphological and histological changes in the testes were observed in both the F1 and F2 generations. Spermatogenesis was dysregulated by an increased proportion of seminiferous tubules at stage I-VI and reduced expression of TH2B and eppin mRNA. Interestingly, gene expression analysis of several markers involved in the regulation and protection of testicular homeostasis revealed significant effects only on the F2 generation. In this generation, uranium exposure also disrupted vitamin D metabolism in the testes.

Uranium may impair testicular function, with more pronounced effects observed in the F2 generation. These findings highlight its potential for multigenerational toxicity and underscore the need for further research into its impact on human reproductive health.