About RSPO / R-Spondin:
R-Spondin 1, also known as RSPO, is a protein that's secreted in humans and encoded by the RSPO1 gene. This protein is found in chromosome 1, and it interacts with WNT4 during female sex development. It also promotes canonical WNT/B catenin signaling, and a lack of function from this protein is believed to cause the female to male sex reversal.
The structure of this protein is as follows: it contains two cysteine-rich, furin-like domains. Alongside this, there is also one thrombospondin type 1 domain.
As mentioned previously, RSPO interacts with WNT4 during female sex development. In fact, it is specifically required for the early development of gonads in both sexes - the testes in men, and the ovaries in women. By interacting with WNT4, cell proliferation is increased, stabilizing B-catenin, which activates targets further downstream.
It has been discovered that a lack of RSPO and B-catenin can lead to defects in vascularization and result in testicular hypoplasia - the incomplete development of the testes. The Leydig cells in the body remain normal, meaning that male to female sex reversal does not necessarily occur.
RSPO1 is absolutely essential in its functions within female sex development for the ovaries. It augments the WNT/B catenin pathway, effectively suppressing and opposing male sex development. This protein is upregulated by the ovaries between 6-9 weeks after fertilization, while the testes downregulate it.
In recent studies using mice, it has also been found that RSPO can be used to treat mucositis, which is a common side effect after many cancer-treating therapies.