# Wolbachia-induced cytoplasmic incompatibility triggers intergenerational dysregulation of the small RNA regulatory network in offspring

## TL;DR

This study shows how Wolbachia bacteria in fruit flies disrupt small RNA networks in offspring, affecting genes related to immunity and reproduction.

## Contribution

The study reveals intergenerational effects of Wolbachia-induced cytoplasmic incompatibility on small RNA regulation in offspring.

## Key findings

- Male offspring from CI crosses show upregulated immune genes and downregulated reproductive genes.
- MicroRNA networks in testes are disrupted, affecting embryonic development and metabolism.
- Increased transposable element activity and piRNA dysregulation are observed in male offspring.

## Abstract

The intracellular symbiont Wolbachia, which is widespread among insects, may induce cytoplasmic incompatibility (CI) between hosts with different infection statuses. Increasing evidence indicates that symbiotic bacteria can influence host reproduction, metabolism, and other biological processes by modulating non-coding small RNAs. However, it is still unclear how Wolbachia-induced CI affects the offspring reproduction. In this study, using Drosophila melanogaster as a model system, small RNA and transcriptome sequencing were conducted on the reproductive systems of the offspring resulting from crosses between Wolbachia-infected males and uninfected females. By comparing F1 males and females to their respective paternal or maternal lines, we identified distinct intergenerational discrepancies. The male offspring of the CI cross showed a significant upregulation of immune-related genes and a notable downregulation of reproductive-related genes. Moreover, the microRNA regulatory network in the testes of the offspring was significantly disrupted, with the target genes directly involved in embryonic development, energy metabolism, immune regulation, and reproductive behavior. Additionally, increased transposable element (TE) expression and piRNA dysregulation were observed in the testes of male offspring. Overall, this study offered new insights into the intergenerational regulatory effects of Wolbachia-induced CI and its potential mechanisms.