title: 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.
authors.affiliation: Department of Reproductive and Developmental Biology,  Institute of Animal Physiology and Genetics AS CR, v.v.i., 277 21 Libechov,  Czech Republic.
authors.forename: Karla
authors.initials: K
authors.lastname: Jarkovska
authors.forename: Helena
authors.initials: H
authors.lastname: Kupcova Skalnikova
authors.forename: Petr
authors.initials: P
authors.lastname: Halada
authors.forename: Rita
authors.initials: R
authors.lastname: Hrabakova
authors.forename: Jiri
authors.initials: J
authors.lastname: Moos
authors.forename: Karel
authors.initials: K
authors.lastname: Rezabek
authors.forename: Suresh Jivan
authors.initials: SJ
authors.lastname: Gadher
authors.forename: Hana
authors.initials: H
authors.lastname: Kovarova
mesh_terms: D003198:Computer Simulation; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects*; D015571:Follicular Fluid / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007704:Kininogens / Q000737:chemistry / Q000378:metabolism; D016471:Ovarian Hyperstimulation Syndrome / Q000209:etiology*; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D007704:Kininogens