Exploring proteomic pathways linked to infertility within endometriosis patients through Mass Spectrometry

Endometriosis, a chronic gynecological disorder affecting over 10% of women of reproductive age globally, causes endometrial tissues to spread outside the uterus, leaving scarring, adhesions, and cysts. Furthermore, studies have shown that 25-50% of women living with endometriosis also experience infertility. Most studies done on the relation between endometriosis and fertility have focused on anatomical irregularities and hormonal imbalances interrupting the ovum and sperm from uniting. However, this raises the question if the cause of infertility within this demographic may also lie within the follicular fluid (fluid produced by the antral follicles that protects a developing egg). In this study, we performed DIA mass spectrometry to identify potentially dysregulated proteins in the follicular fluid affecting ovum viability in 9 endometriosis patients and 5 patients seeking IVF treatment (set as a control). We used nanoparticles to ensure deeper proteome coverage and the ability to quantify low abundance proteins within the follicular fluid. We found 50 unique endometriosis proteins, 353 shared proteins, 437 control specific proteins between our two groups. To identify the key biological processes that are different between the upregulated and downregulated proteins, we used WebGestalt over- representation analysis. In the downregulated protein group, the biological processes included humoral immune response, cell killing, and protein maturation. The upregulated protein group biological processes were acute inflammation, metal ion transport, and tissue migration. Our results suggest that the follicular fluid proteome may be used to identify biomarkers related to infertility and endometriosis.