Development of ovarian hyperstimulation syndrome: interrogation of key proteins and biological processes in human follicular fluid of women undergoing in vitro fertilization

Abstract

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication and potentially life-threatening condition resulting from excessive ovarian stimulation during assisted reproductive technologies. Our aim was to identify candidate proteins in follicular fluid (FF) using various proteomic approaches which may help to identify patients at risk of OHSS. We analysed the proteome alterations in FF from patients suffering from severe forms of OHSS (OHSS+) compared with a control group of women without or with only mild signs of OHSS (OHSS-). The 12 abundant proteins of FF were removed using an immunoaffinity system. Pools of remaining depleted proteins were applied to the two-dimensional (2D) electrophoresis and 2D liquid chromatography and proteins in differentially expressed protein spots/fractions were identified by mass spectrometry. Among a total of 19 candidate proteins differentially expressed (P< 0.05) between OHSS+ and OHSS- FF samples, three proteins, namely ceruloplasmin, complement C3 and kininogen-1, were found using both 2D techniques. Computer modelling highlighted the important role of kininogen-1 as an anchor for mediated interactions with other identified proteins including ferritin light chain and ceruloplasmin, hepatocyte growth factor-like protein, as well as complement C3 and gelsolin, thus linking various biological processes including inflammation and angiogenesis, iron transport and storage, blood coagulation, innate immunity, cell adhesion and actin filament polymerization. The delineation of such processes may allow the development of informed corrective therapeutic intervention in patients at risk of OHSS and a set of key proteins of the FF may be helpful as potential biomarkers for monitoring IVF therapy.

Preliminary proteomic analysis on the alterations in follicular fluid proteins from women undergoing natural cycles or controlled ovarian hyperstimulation

“…The P-value was calculated using the righttailed Fisher's exact test. Bars represent − log (P-value) for significance ovarian stimulation has been demonstrated to induce aberrant expression of FF proteins, such as C3, associated with inflammation, iron transport and storage, blood coagulation, and innate immunity in women who developed ovarian hyperstimulation syndrome [28]. In this study, the increased levels of C3 and ZAG in the COH FF suggest that the patients might have had aberrant immune and inflammatory responses during the cycle.…”

The Use of Proteomics in Assisted Reproduction

“…In a recent study by Bianchi et al in the follicular fluid of six women undergoing IVF after ovarian hyperstimulation, 43 unique proteins were identified, functionally classified in 5 groups (inflammation and regulation of acute-phase, complement and coagulation, response to wounding, protein-lipid complex/lipid metabolism and transport, and cytoskeleton organization) and cross-linked to generate a tightly controlled pathway depicting the initial inflammatory-like phase of ovulation, also described in previous studies (87,88), further accentuated by ART superovulation, followed by tissue remodeling that is crucial for the formation of corpus luteum. A1 antithrypsin was differentially expressed in the follicular fluid and sera of women in this cohort (89).…”

Complement C3 and anti-testosterone antibody in the 150 kDa Bali cattle (Bos sondaicus/javanicus) subordinate follicular fluid peptide observed using MALDI-TOF/TOF-MS

“…The regulation of C3 expression in malignant cells is not well understood, similarly, the involvements of the cascade in the innate immunity of follicular fluids still need to be explored. Jarkovska et al (2011) have shown the role of complement in oocyte maturation. They demonstrated that activation of complement resulted in the deficiency of vascular endothelial growth factor (VEGF), in fact VEGF is needed for oocyte maturation.…”