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bioRxiv · 10.1101/2025.09.16.676617

DAF-18/PTEN prevents oocyte wastage in spermless C. elegans hermaphrodites by blocking spermatheca neck dilation through RHO-1/RhoA disinhibition

Deng, J.·Chaudhari, A. M.·Olivier, G.·Vincent, R.·Dufour, B.·Martel, P.-O.·Simard, M. J.·Narbonne, P.
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Abstract

Loss of the Phosphatase and TENsin homolog PTEN drives cancer in humans. In C. elegans hermaphrodites that lack sperm, the PTEN ortholog DAF-18 is required for oocyte quiescence and their proximal accumulation, along with the concomitant homeostatic downregulation of germline stem cell proliferation. As such, spermless daf-18(o) mutants undergo full-scale oogenesis and ovulation in a futile manner, wasting all produced oocytes. When oocyte laying is prevented in these mutants, oocytes hyperaccumulate to form differentiated benign tumors. Here, we show that daf-18 expression in the spermatheca neck myoepithelium is sufficient to induce oocyte arrest and homeostatic downregulation of germline stem cell proliferation in spermless hermaphrodites, altogether prohibiting tumorigenesis. We demonstrate that DAF-18 promotes spermatheca neck contractility through limiting PIP3 levels and AKT activity, preventing the latter from inactivating RHO-1/RhoA by direct phosphorylation at a conserved site. Loss of PTEN may therefore promote benign tumorigenesis in humans through similar cell non-autonomous effects.

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Deng, J., Chaudhari, A. M., Olivier, G., Vincent, R., Dufour, B., Martel, P.-O., Simard, M. J., Narbonne, P.. 2025-09-18. DAF-18/PTEN prevents oocyte wastage in spermless C. elegans hermaphrodites by blocking spermatheca neck dilation through RHO-1/RhoA disinhibition. https://doi.org/10.1101/2025.09.16.676617

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