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Infection with Toxoplasma gondii induces inheritable epigenetic changes in mouse sperm

ABSTRACT: In this study we sought to analyse if infection with the common human parasite Toxoplasma gondii aftered sperm epigenetics by sequecing small RNA from parasite infected and mock infected mice. Epigenetic changes in sperm is a well described process of inheritanece of paternal environmental experiences to their progeny. Using high throughput Illumina sequencing, we revealed differences between the sperm small RNA profiles of Toxoplasma-infected and control animals . We found 25.88% of small RNAs were differentially expressed after correcting for false discovery rate, of which 9.21% and 16.67% were up- and down-regulated, respectively. Further quantitative analysis revealed enriched small RNA load in our samples and biotypes composition analysis showed a majority tRNA population followed by miRNA and piRNA populations, while the rest contained various other small RNA transcripts.When we looked at miRNA changes between Toxoplasma-infected and control samples, we found that of the total miRNA mapped (585), 174 were differentially expressed in the Toxoplasma-infected group (FDR < 0.05) of which 35 were down- and 75 were up-regulated with a Log2FC < -2 and > 2, respectively. Lastly, using gene enrichment analysis, we identified pathways regulated by small RNA’s that are differentially expressed and found that small RNA’s targeted distinct biological pathways.

ORGANISM(S): Mus musculus

PROVIDER: GSE137224 | GEO | 2021/02/25

REPOSITORIES: GEO

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Project description:Toxoplasma gondii is a globally distributed obligate intracellular parasite which can cause zoonotic toxoplasmosis with great harms. The average death time of mice that infected with Toxoplasma gondii RH strain tachyzoites recovered from the liquid nitrogen was shortened after multiple generations. It has been reported that the parasite is in a state of static virulence during cryopreservation and the virulence of the protozoan parasite can be enhanced after continuous passages in hosts under laboratory conditions. However, no research has been conducted to elucidate its biological mechanism. Herein, we sequenced the T. gondii transcriptome using RNA-Seq technology and performed de novo assembly to investigated the virulence factors expression changes by comparing gene expression profiles between incipiently recovered and completely resuscitated tachyzoites. Transcriptome analysis identified 1,951 differentially expressed transcripts in infected liver, of which 1,752 were significantly downregulated and 199 upregulated. We identified many differentially expressed proteins and genes, including serine/threonine kinase, calnexin, myosin and microtubule-associated protein which have previously been reported to be either involved in cell adhesion, parasite gliding or participate in cell invasion. The great majority of the virulence factors including microneme proteins, rhoptry proteins and dense granule proteins were upregulated in fully recovered tachyzoites. The enhanced virulence of recovered Toxoplasma gondii RH strain from the liquid nitrogen is associated with the up-regulated expression of MICs, ROPs and GRAs. Our data will facilitate future genomic research and in-depth annotation of Toxoplasma gondii RH strain genomes. This study provides a profile of the candidate genes that are suspected to be involved with virulence enhancement of recovered Toxoplasma gondii RH strain tachyzoites. Many further studies should be carried out to confirm the function of the candidate genes. Moreover, the preliminary identification of genes and pathways exhibiting differential expression in complete resuscitation stage may further our general understanding of virulence enhancement in this parasite.

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Infection with Toxoplasma gondii induces inheritable epigenetic changes in mouse sperm

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