PILISSAO, LUIZ EDUARDO et al. (2021) International Worm Meeting "Reprotoxicity induced by Acute exposure to Aqueous Root Extract of Peruvian Maca (Lepidium meyenii) in Caenorhabditis elegans"

da Silva, Andressa Tassinari, Avila, Daiana Silva, Rodrigues, Cristiane Freitas, Puntel, Robson Luiz, Paim, Clesio Soldatelli, Porto, Douglas, PILISSAO, LUIZ EDUARDO, Denardin, Cristiane Casagrande, Brabo, Gabriela Rossi

[International Worm Meeting, 2021]

Ethnopharmacological relevance: Maca (Lepidium meyenii) has been used in folk medicine to treat fertility disturbances. However, there are few scientific evidences validating this use or assuring extract safety. Aim of the study: Hence, in this study we tested the reproduction safety of this extract in Caenorhabditis elegans. Materials and Methods: Root maca powder, obtained from local commerce, was used to prepare the aqueous extract. Worms were acutely exposed to maca extracts (40, 120, 240 and 330 mug/mul), based on human consumption of 1g capsules of the same powder. 48h after treatments, assays were conducted. Results: Maca extract caused a significant decrease in total number of eggs and in the number of eggs per worm from. These effects were associated to increased lipid peroxidation, reduced triacylglycerol levels and also vitellogenin-2 expression, besides increase in the number of apoptotic germline cells. We have detected and quantified alkaloids in this maca extract, which presence could be related to this toxicity. Conclusions: Collectively, our data suggest that maca extract exposure causes reproductive toxicity to worms which could be, at least in part, associated to both an increase in apoptosis of germline cells and also to a decrease in vitellogenin expression, needed for egg yolk production, and consequently, successful reproduction.

Pereirinha, Joana et al. (2021) International Worm Meeting "Investigation of the role of the protein complex PETISCO in C. elegans embryonic viability"

Cordeiro Rodrigues, Ricardo, Ketting, Rene, Pereirinha, Joana

[International Worm Meeting, 2021]

The PIWI/piRNA pathway is a highly conserved small RNA pathway. Central to the pathway is an RNA silencing complex made of an Argonaute protein of the PIWI clade and PIWI-interacting RNAs (piRNAs), which target transposons in animal germlines. In C. elegans, piRNAs also target endogenous protein-coding genes, making the PIWI/piRNA pathway an important regulator of gene expression. C. elegans piRNAs are referred to as 21U RNAs since they are 21 nucleotides long and have a 5' bias for uridine monophosphate. We recently identified a protein complex driving 21U RNA biogenesis, which we named PETISCO (Cordeiro Rodrigues et al., 2019). However, we found that PETISCO can have different functions depending on whether it interacts with the proteins PID-1 (PiRNA Induced silencing Defective) or TOST-1 (Twenty-One U antagoniST). PETISCO:PID-1 complex participates in the 21U RNA biogenesis by interaction and stabilization of the 21U RNA precursors. While being important for gene regulation, the loss of PID-1 is not embryonic lethal. In contrast, PETISCO:TOST-1 is not involved in 21U RNA biogenesis but is nevertheless essential for embryonic development of the subsequent generation (Cordeiro Rodrigues et al., 2019; Zeng et al., 2019). The molecular function of this complex as well as the observed lethality effect is not yet understood. Based on preliminary data, we hypothesize that the PETISCO:TOST-1 complex regulates replication-dependent histones mRNA expression. In this study we want to characterize the PETISCO::TOST-1 complex and dissect its role in embryogenesis. This study would highlight the role of 21U RNA pathway factors in gene expression and C. elegans embryonic development.

Schroeder, Frank et al. (2021) International Worm Meeting "Carboxyesterases and intestinal granules in the biosynthesis of novel families of nematode small molecule signals"

Wrobel, Chester, Schroeder, Frank, Sternberg, Paul, Cohen, Sarah

[International Worm Meeting, 2021]

Signaling molecules derived from attachment of diverse primary metabolic building blocks to ascarosides play a central role in the life history of C. elegans and other nematodes; however, the extent to which various inter- and intra-organismal signaling pathways are controlled by small molecules is unclear. Using comparative metabolomics, we show that a pathway mediating formation of intestinal lysosome-related organelles (LROs) is required for biosynthesis of a large library of small molecules, including most modular ascarosides as well as previously undescribed modular glucosides (1). Similar to modular ascarosides, the modular glucosides are derived from highly selective assembly of moieties from nucleoside, amino acid, neurotransmitter, and lipid metabolism. We further show that a family of carboxylesterases (CEST's) that localize to intestinal organelles are required for the assembly of both modular ascarosides and glucosides, suggesting that modular glucosides, like the ascarosides, serve signaling functions. For example, biosynthesis of some modular glucosides is starkly upregulated in long-lived daf-2 mutants, suggesting that insulin signaling is modulated by small molecules produced in a lysosome-dependent manner. Parallel studies in C. briggsae and other nematode species indicate that assembly of modular metabolites via CEST enzymes is widely conserved in nematodes. Further exploration of LRO function and cest homologs in C. elegans and other animals may reveal additional new compound families and signaling paradigms. (1) H. H. Le, C. J. J. Wrobel, S. M. Cohen, J. Yu, H. Park, M. J. Helf, B. J. Curtis, P. R. Rodrigues, P. W. Sternberg, F. C. Schroeder. Modular metabolite assembly in C. elegans depends on carboxylesterases and formation of lysosome-related organelles. eLife, 9, e61886, 2020.