title: Hypocoagulable state of human preovulatory ovarian follicular fluid: role of sulfated proteoglycan and tissue factor pathway inhibitor in the fluid.
abstract: Ovulation accompanied by tissue damage can cause an increase in the level of tissue factor (TF) in the follicular fluid, triggering the extrinsic coagulation pathway. However, follicular fluid must block fibrin formation and maintain fluidity until the release of the oocyte at ovulation. The combination of sulfated proteoglycan, antithrombin, and TF pathway inhibitor (TFPI) appears to play a critical role in the hypocoagulability of human follicular fluid. When compared with plasma, folicular fluid differs markedly in the levels of a number of important coagulation proteins. Principal among these are 15-fold, 13-fold, and 3.7-fold increases in free TFPI, thrombin-antithrombin complex, and TF, respectively. The excessively prolonged activated partial thromboplastin time (APTT) and prothrombin time (PT) of human ovarian follicular fluid appear to be primarily due to high concentrations of sulfated proteoglycans, which accelerate the inactivation of thrombin and the anti-Xa activity of TFPI. Thus, heparitinase treatment shortened the clotting times of follicular fluid and reduced the inhibition of thrombin by the proteoglycan fraction combined with a fraction containing antithrombin. The remaining prolongation of APTT and PT may be caused by high levels of free TFPI in follicular fluid, which were confirmed by Northern blotting analysis, demonstrating TFPI mRNA expression by granulosa cells.
authors.affiliation: Department of Obstetrics, Kobe City General Hospital, Kobe 650, Japan. shimada8810@hkg.odn.ne.jp
authors.forename: H
authors.initials: H
authors.lastname: Shimada
authors.forename: S
authors.initials: S
authors.lastname: Kasakura
authors.forename: M
authors.initials: M
authors.lastname: Shiotani
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Ikeuchi
authors.forename: T
authors.initials: T
authors.lastname: Hoshino
authors.forename: T
authors.initials: T
authors.lastname: Komatsu
authors.forename: Y
authors.initials: Y
authors.lastname: Ihara
authors.forename: M
authors.initials: M
authors.lastname: Sohma
authors.forename: Y
authors.initials: Y
authors.lastname: Maeda
authors.forename: R
authors.initials: R
authors.lastname: Matsuura
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.forename: C
authors.initials: C
authors.lastname: Hine
authors.forename: N
authors.initials: N
authors.lastname: Ohkura
authors.forename: H
authors.initials: H
authors.lastname: Kato
mesh_terms: D000990:Antithrombin III / Q000032:analysis; D000991:Antithrombins / Q000032:analysis / Q000494:pharmacology; D015152:Blotting, Northern; D002850:Chromatography, Gel; D015951:Factor Xa / Q000378:metabolism; D005260:Female; D015571:Follicular Fluid / Q000737:chemistry / Q000502:physiology*; D006107:Granulosa Cells / Q000737:chemistry; D006801:Humans; D008074:Lipoproteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D010060:Ovulation; D010314:Partial Thromboplastin Time; D010447:Peptide Hydrolases / Q000032:analysis; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D011509:Proteoglycans / Q000494:pharmacology / Q000502:physiology*; D011517:Prothrombin Time; D012333:RNA, Messenger / Q000032:analysis; D013431:Sulfates / Q000378:metabolism*; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism; D013925:Thromboplastin / Q000032:analysis
chemical_list: D000991:Antithrombins; D008074:Lipoproteins; D011509:Proteoglycans; D012333:RNA, Messenger; D013431:Sulfates; C046193:antithrombin III-protease complex; C051928:lipoprotein-associated coagulation inhibitor; D000990:Antithrombin III; D013925:Thromboplastin; D010447:Peptide Hydrolases; D013917:Thrombin; D015951:Factor Xa; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase