The role of the CCN family of proteins in female reproduction.

The CCN family of proteins consists of six high homologous matricellular proteins which act predominantly by binding to heparin sulphate proteoglycan and a variety of integrins. Interestingly, CCN proteins are regulated by ovarian steroid hormones and are able to adapt to changes in oxygen concentration, which is a necessary condition for successful implantation. CCN1 is involved in processes of angiogenesis within reproductive systems, thereby potentially contributing to diseases such as endometriosis and disturbed angiogenesis in the placenta and fetus. In the ovary, CCN2 is the key factor for follicular development, ovulation and corpora luteal luteolysis, and its deletion leads to fertility defects. CCN1, CCN2 and CCN3 seem to be regulators for human trophoblast proliferation and migration, but with CCN2 acting as a counterweight. Alterations in the expression of these three proteins could contribute to the shallow invasion properties observed in preeclampsia. Little is known about the role of CCN4-6 in the reproductive organs. The ability of CCN1, CCN2 and CCN3 to interact with numerous receptors enables them to adapt their biological function rapidly to the continuous remodelling of the reproductive organs and in the development of the placenta. The CCN proteins mediate their specific cell physiological function through the receptor type of their binding partner followed by a defined signalling cascade. Because of their partly overlapping expression patterns, they could act in a concert synergistically or in an opposite way within the reproductive organs. Imbalances in their expression levels are correlated to different human reproductive diseases, such as endometriosis and preeclampsia.