Trpv4 links environmental temperature to testicular differentiation in hermaphroditic ricefield eel

The ricefield eel, a significant freshwater fish species in China's aquaculture industry, undergoes a unique sex change process that scientists are now beginning to understand. This protogynous hermaphrodite fish can transform its ovaries into testes in response to warmer environmental temperatures. Key to this transformation is the Trpv4 (Transient Receptor Potential Vanilloid 4) channel, a calcium-permeable cation channel found in the fish's gonadal somatic cells.

The Trpv4 channel is highly responsive to changes in ambient temperature, acting as a molecular link between environmental conditions and the fish's sex differentiation process.

For female ricefield eels kept in cool temperatures, the injection of a Trpv4 agonist into their ovaries triggers a significant increase in genes associated with male pathway genes. Conversely, when exposed to warmer temperatures, inhibiting Trpv4 or knocking down the corresponding gene expression suppresses the activation of these male genes. This suggests that Trpv4 plays a crucial role in translating temperature changes into sex differentiation signals within the fish.

The Trpv4 channel's activity ultimately drives a signaling cascade involving pStat3 (phospho-Ser307 Stat3), a signaling molecule that plays a critical role in transmitting the effects of Trpv4-controlled calcium signaling into the fish's sex determination process. By blocking the activity of pStat3, scientists were able to prevent the warm temperature-induced upregulation of testicular differentiation genes, underscoring pStat3's role as a mediator in this process.

Conversely, activating pStat3 alone was found to promote the expression of male genes in the ovaries, even when Trpv4 was inhibited.

Further investigation revealed that pStat3 can bind and activate jmjd3/kdm6b, a gene known to activate the dmrt1 gene, a key player in male sexual differentiation. This connection provides a clear molecular pathway (Trpv4-pStat3-Kdm6b-dmrt1) by which environmental temperature influences testicular differentiation in ricefield eels.

The discovery of this Trpv4-pStat3-Kdm6b- dmrt1 axis offers new insights into the molecular mechanisms behind the natural sex change observed in ricefield eels, potentially paving the way for improved sex control strategies in aquaculture practices.