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- Ramesh, Rashmi, 1984-, et al.
(författare)
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Dietary Sugar Shifts Mitochondrial Metabolism and Small RNA Biogenesis in Sperm
- 2023
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Ingår i: Antioxidants and Redox Signaling. - : MARY ANN LIEBERT, INC. - 1523-0864 .- 1557-7716. ; 38:16-18, s. 1167-1183
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Increasing concentrations of dietary sugar results in a linear accumulation of triglycerides in male Drosophila, while inducing a U-shaped obesity response in their offspring. Here, using a combination of proteomics and small RNA (sRNA) sequencing, we aimed at understanding the molecular underpinning in sperm for such plasticity.Results: Proteomic analysis of seminal vesicles revealed that increasing concentrations of dietary sugar resulted in a bell-shaped induction of proteins involved in metabolic/redox regulation. Using stains and in vivo redox reporter flies, this pattern could be explained by changes in sperm production of reactive oxygen species (ROS), more exactly mitochondria-derived H2O2. By quenching ROS with the antioxidant N-acetyl cysteine and performing sRNA-seq on sperm, we found that sperm miRNA is increased in response to ROS. Moreover, we found sperm mitosRNA to be increased in high-sugar diet conditions (independent of ROS). Reanalyzing our previously published data revealed a similar global upregulation of human sperm mitosRNA in response to a high-sugar diet, suggesting evolutionary conserved mechanisms.Innovation: This work highlights a fast response to dietary sugar in mitochondria-produced H2O2 in Drosophila sperm and identifies redox-sensitive miRNA downstream of this event.Conclusions: Our data support a model where changes in the sperm mitochondria in response to dietary sugar are the primary event, and changes in redox homoeostasis are secondary to mitochondrial ROS production. These data provide multiple candidates for paternal intergenerational metabolic responses as well as potential biomarkers for human male fertility.
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| 2. |
- Örkenby, Lovisa, 1992-
(författare)
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Small non-coding RNA in early fly development : plasticity, interactions and improved bioinformatic tools
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- At fertilization, the male and female pronuclei undergo a transformation from germline to pluripotency as they fuse, marking the beginning of Drosophila embryogenesis. As the parental contributions decrease, the zygote takes control of its genome in a process called the maternal-to-zygotic transition (MZT). Several small non-coding RNAs (sncRNAs), a very large and diverse group of RNAs, have regulatory roles during this transition. This includes for example microRNAs (miRNAs) and piwi-interacting RNAs (piRNAs). Regulation by miRNAs mainly occurs through mediating maternal mRNA degradation, while piRNAs operate by repressing transposable elements (TEs) and regulating the nanos-induced embryonic body axis determination.In this thesis, the complex and dynamic field of early Drosophila embryogenesis and sncRNAs are put in relation to the included papers. In Paper I, I explored the most stress-sensitive embryonic period and found that stress before the midblastula transition retains maternal miRNAs. These miRNAs impact zygotic gene activation by modulating the boundary factor Elba1, leading to compromised transcription control. Paper III examines the piRNA population during MZT. I find differences of unique piRNA sequences in embryos of different ages but not in target preferences, potentially highlighting the importance of constant repression of certain TEs. Paper II addresses specific difficulties with sncRNA seq data analysis and presents a bioinformatic framework to improve these analyses using a sequence-based strategy.This thesis highlights the intricate interplay of sncRNAs in the critical period of early Drosophila embryogenesis and offers insights into their regulatory roles.
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