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ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Microbial Symbioses

Wolbachia-Induced Cytoplasmic Incompatibility Triggers Intergenerational Dysregulation of the Small RNA Regulatory Network in Offspring

  • 1. Shandong University of Technology, Zibo, China

  • 2. Zibo Central Hospital, Shandong, China

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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.

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Keywords

Cytoplasmic incompatibility, immune, miRNA, piRNA, Wolbachia

Received

10 December 2025

Accepted

30 January 2026

Copyright

© 2026 Dou and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Tian-chu Li

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