Polycystic Ovary Syndrome (PCOS) is the most common reproductive endocrine disorder among women of reproductive age, which is one of the main causes of anovulatory infertility.During the normal follicular development process, granulosa cells (GCs) are the most important cells, which directly affect the development of the oocyte. Several studies have shown that the GCs dysfunction can result in abnormal follicular development in women with PCOS.It is worth noting that aberrant changes in the ovarian microenvironment, such as oxidative stress and inflammation, can impair the physiological state of GCs,which may also be themain cause of subsequent PCOS follicular development disorders.
Chitosan oligosaccharide (COS) is mainly derived from crustaceans and also exists in fungi, insects, cell membranes of algae and cell walls of higher plants.Several studies have reported that COS can act as a potentfree radical scavenger to balance biomoleculesin oxidative and antioxidant processes in cellular systems and inhibit intracellular ROS formation . Additionally, COS inhibits the inflammatory response of macrophages induced by lipopolysaccharide (LPS) and reduces the expression of pro-inflammatory cytokinesTNF-aand IL-6 .More importantly, our team found that COS has a protective effect on hydrogen peroxide- (H2O2-) stimulated oxidative damage in human ovarian granulosa cell line (KGN) , and COS can promote the proliferation of ovarian germ stem cells and reshape the ovarian function by improving the ovarian microenvironment and stimulating the secretion of immune related factors .
In this study，human ovarian granulosa cell line (KGN) cells were used to verify the anti-inflammatory and anti-oxidative stress effects of chitosan oligosaccharide (COS) on GCs, we found that COS can increase the expression of antiinflammatory factors TGF-b1 and IL-10 and decrease the expression of pro-inflammatory factors TNFa and IL-6, as well as promote the proliferation of GCs. COS can reduce the level of reactive oxygen species in GCs under oxidative stress by inhibiting the expression of HIF-1a and VEGFA and suppressing the apoptosis of GCs induced by oxidative stress. Finding COS new pharmacological application in infertility treatment is expected to provide a new therapeutic treatment for clinical PCOS patients by enhancing the GCs proliferative capacity and decreasing their apoptosis level via improving the inflammation and oxidative stress of GCs into a suitable intensity.
Reference:Chitosan oligosaccharide improves ovarian granulosa cells inflammation and oxidative stress in patients with polycystic ovary syndrome