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

## TL;DR

Exposure to low levels of uranium in rats causes testicular dysfunction, especially in the second generation, affecting sperm production and hormone balance.

## Contribution

The study reveals stronger multigenerational testicular dysregulation in F2 rats exposed to non-nephrotoxic uranium.

## Key findings

- Uranium exposure disrupted spermatogenesis and steroidogenesis in multiple generations of rats.
- Significant testicular dysregulation was observed only in the F2 generation, including altered vitamin D metabolism.
- Morphological and histological changes were noted in F1 and F2 generations, indicating reproductive toxicity.

## Abstract

•Exposure to a non-nephrotoxic dose of uranium impacts testicular function in rats.•Multigenerational exposure (F0–F2) in rats used to assess reproductive effects.•Major dysregulations observed in F2 rats.•Clarified effects on spermatogenesis, steroidogenesis and testicular homeostasis.•Findings contribute to risk assessment and radiation protection.

Exposure to a non-nephrotoxic dose of uranium impacts testicular function in rats.

Multigenerational exposure (F0–F2) in rats used to assess reproductive effects.

Major dysregulations observed in F2 rats.

Clarified effects on spermatogenesis, steroidogenesis and testicular homeostasis.

Findings contribute to risk assessment and radiation protection.

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.