Muscle-derived exophers promote reproductive fitness

Organismal functionality and reproduction depend on metabolic rewiring and balanced energy resources. However, the crosstalk between organismal homeostasis and fecundity and the associated paracrine signaling mechanisms are still poorly understood. Using Caenorhabditis elegans, we discovered that large extracellular vesicles (known as exophers) previously found to remove damaged subcellular elements in neurons and cardiomyocytes are released by body wall muscles (BWM) to support embryonic growth. Exopher formation (exopheresis) by BWM is sex-specific and a non-cell autonomous process regulated by developing embryos in the uterus. Embryo-derived factors induce the production of exophers that transport yolk proteins produced in the BWM and ultimately deliver them to newly formed oocytes. Consequently, offspring of mothers with a high number of muscle-derived exophers grew faster. We propose that the primary role of muscular exopheresis is to stimulate reproductive capacity, thereby influencing the adaptation of worm populations to the current environmental conditions.

Work in the W.P. laboratory was mainly funded by the Foundation for Polish Science co-financed by the European Union under the European Regional Development Fund (grant POIR.04.04.00-00-5EAB/18-00 to K.B., K.K. and W.P.) and additionally supported by the European Molecular Biology Organization (EMBO Installation Grant No. 3916 to W.P.) and the Deutsche Forschungsgemeinschaft (DFG FOR 2743 to W.P.). The research leading to part of these results has received funding from the Norwegian Financial Mechanism 2014-2021 and operated by the Polish National Science Center under the project contract no UMO-2019/34/H/NZ3/00691 (M.P.). Work in the A.C. laboratory was funded by the "Regenerative Mechanisms for Health" project MAB/2017/2 (A.C. and M.T.) carried out within the International Research Agendas programme of the Foundation for Polish Science co-financed by the European Union under the European Regional Development Fund and was supported by a POLONEZ Fellowship of National Science Centre, Poland, 2016/21/P/NZ3/03891 (M.T.), within European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 665778. Work in the M. T. Laboratory was funded by a National Science Centre SONATA grant (2019/35/D/NZ3/04091).