In worms, the gene regulator NHR-49 prevents oocytes from maturing without sperm and preserves the organism’s reserves

In worms, the gene regulator NHR-49 prevents oocytes from maturing without sperm and preserves the organism’s reserves

On August 22, Nature Communications published a study examining how nutrition influences the decision to invest resources in reproduction in the roundworm C. elegans. When nhr-49 function was disrupted, oocytes matured and were released without sperm. The worms lost yolk and fat reserves in the process, and their lifespan decreased.

In C. elegans, sperm provides the signal that initiates reproduction. Until that signal arrives, oocytes remain in the oviduct. In a 2025 study, the same group found that sperm-depleted strains accumulated more fat and lived longer at 25 °C. The new study investigates the molecular mechanism that maintains this waiting state.

The researchers identified NHR-49, a protein that regulates genes involved in nutrition and fat metabolism. They studied sperm-depleted strains. Loss of nhr-49 function triggered oocyte maturation and ovulation, causing the worms to lay unfertilized oocytes. Starvation slowed the division of cells that give rise to oocytes in normal worms, but this pause did not occur in nhr-49 mutants. NHR-49 therefore connects nutritional status to the organism’s decision about whether to continue reproduction.

The researchers separated the initiation of oocyte development from its cost in resources. The worm’s intestine produces yolk, which oocytes take up through the receptor protein RME-2. When RME-2 was suppressed, the yolk remained in the body, fat reserves were largely restored, and lifespan recovered partially. The number of unfertilized oocytes laid did not change significantly. Yolk transfer therefore accounts for part of the lifespan reduction caused by activating oocytes without a sperm signal.

Tissue-specific experiments showed that NHR-49 acts mainly in the gonadal sheath cells, which form the tissue surrounding the germ cells. Restoring NHR-49 in these cells partially reduced the abnormal egg laying. The gsa-1 gene encodes GSA-1, a protein involved in transmitting the sperm signal to the oocyte. NHR-49 bound to DNA regions near gsa-1. Suppressing gsa-1 reduced abnormal egg laying and restored yolk retention. In the authors’ model, NHR-49 restrains this pathway at least in part, thereby raising the threshold for oocyte activation.

In worms, the use of yolk by oocytes activated without a sperm signal accounts for part of the reduction in lifespan.