Proteome Mining of Human Follicular Fluid Reveals a Crucial Role of Complement Cascade and Key Biological Pathways in Women Undergoing in Vitro Fertilization

Abstract

In vitro fertilization (IVF) is fraught with problems and currently proteomics approaches are being tried out to examine the microenvironment of the follicle in order to assess biological and immunological parameters that may affect its development. Additionally, better understanding of reproductive process may help increase IVF birth rate per embryo transfer and at the same time avoid spontaneous miscarriages or life threatening conditions such as ovarian hyperstimulation syndrome. The primary aim of this study was to search for specific differences in protein composition of human follicular fluid (HFF) and plasma in order to identify proteins that accumulate or are absent in HFF. Depletion of abundant proteins combined with multidimensional protein fractionation allowed the study of middle- and lower-abundance proteins. Paired comparison study examining HFF with plasma/serum from women undergoing successful IVF revealed important differences in the protein composition which may improve our knowledge of the follicular microenvironment and its biological role. This study showed involvement of innate immune function of complement cascade in HFF. Complement inhibition and the presence of C-terminal fragment of perlecan suggested possible links to angiogenesis which is a vital process in folliculogenesis and placental development. Differences in proteins associated with blood coagulation were also found in the follicular milieu. Several specific proteins were observed, many of which have not yet been associated with follicle/oocyte maturation. These proteins together with their regulatory pathways may play a vital role in the reproductive process.

A Proteomic Analysis of Human Follicular Fluid: Comparison between Younger and Older Women with Normal FSH Levels

“…Based on previous studies in ART, the success rate declines with age. There is a lack of assessment of oocyte quality or ability to predict the success of IVF treatment [46]. Because clinical outcomes of IVF are highly dependent on age, we sought to identify the differences in the total number of retrieved mature oocytes.…”

Oocyte environment: follicular fluid and cumulus cells are critical for oocyte health

“…Removal of plasma proteins from the follicular fluid of women undergoing successful IVF, however, shows the remaining proteome to contain proteins with specific biological processes, involving complement and lipid metabolism (143). Further evaluation of the follicular fluid proteome relative to IVF outcome shows a greater number of proteins involving biosynthetic pathways that correspond with oocytes yielding clinical pregnancies versus negative pregnancy outcomes (144).…”

A proteomic analysis of human follicular fluid: comparison between fertilized oocytes and non-fertilized oocytes in the same patient

“…Proteomics is helpful not only for identifying new disease-related biomarkers, but also for improving understanding of the pathophysiology of diseases. The application of proteomic analyses in medical research is intended to enrich a targetsetofdisease-relatedproteins.Inthegynecologicfield,this technique has been applied in the analysis of amniotic [5,10] and follicular fluid [3,11,18].…”