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

Abstract

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.