# Progeny effects of rotenone exposure depend on parental toxicity

## TL;DR

Exposure to rotenone in parents can affect the health of their offspring, even at low concentrations that don't harm the parents.

## Contribution

The study shows that even low-level parental exposure to mitochondrial toxins can lead to subtle but measurable effects in offspring.

## Key findings

- High rotenone exposure in parents caused significant changes in growth, mitochondrial function, and gene expression.
- Low rotenone exposure still led to minor effects in offspring, including reduced egg size and increased sensitivity to later stressors.
- Offspring from both high and low exposure showed altered responses to secondary rotenone challenges.

## Abstract

Parental exposure to toxicants can affect progeny health. However, laboratory studies often employ exposures that result in loading of pollutants to gametes or toxic effects to parents, which could indirectly affect germ cell or gamete health. Here, we took advantage of the biology of Caenorhabditis elegans to carry out a study in which we minimized the potential for maternal loading of toxicants, and used an exposure paradigm that either did (high concentration) or did not (low concentration) significantly impact the health of the P0 generation. We hypothesized that parental exposure to mitochondrial toxicants during germ cell and gamete development, at levels not causing P0 toxicity, would result in altered mitochondria and organismal health in offspring. In the P0 generation, a high rotenone concentration altered growth, mitochondrial respiration, gene expression, induction of the mitochondrial unfolded protein response, and susceptibility to dopaminergic neurodegeneration induced by a chemical rechallenge later in life. However, we observed minor or no effects in P0 at a low concentration. In high-exposure F1 offspring, we observed altered embryo size, larval developmental stage distribution, spare respiratory capacity, heat shock protein expression, and dopaminergic neurodegeneration after a secondary rotenone challenge. The only effects observed in the F1 offspring of the low exposure were a 1.7% decrease in egg size (size later in development was normal), and moderate evidence of a slightly increased sensitivity to heat shock protein expression and dopaminergic neurodegeneration caused by a secondary later-in-life rotenone exposure. We recommend that parental toxicity be carefully assessed to contextualize offspring outcomes.