Increased platelet factor 4 and aberrant permeability of follicular fluid in PCOS

Increased platelet factor 4 and aberrant permeability of follicular fluid in PCOS
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DOI:
10.1016/j.jfma.2018.05.002
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发表时间:
2019-01-01
影响因子:
3.2
通讯作者:
Chen, Mei-Jou
Chen, Mei-Jou
中科院分区:
医学3区
文献类型:
--
作者:
Huang, Chu-Chun;Chou, Chia-Hung;Chen, Mei-Jou

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背景/目的:卵泡发生异常是多囊卵巢综合征(PCOS)的主要表现之一,卵泡壁的通透性被认为与卵泡的正常生长有关。然而,卵泡内通透性是否发生改变是多囊卵巢综合征的基础尚不清楚。2014-2015年间,13例接受体外受精-胚胎移植(IVF-ET)的多囊卵巢综合征患者。11例因男性因素和/或输卵管因素不孕而行IVF-ET的排卵正常患者作为对照组。采用人脐静脉内皮细胞单层通透性实验评价卵泡液对内皮细胞通透性的影响。结果:多囊卵巢综合征患者卵泡内皮细胞通透性明显低于对照组(46%+/-12%vs.58%+/-9%,P=0.023)。在55个血管生成相关蛋白中,多囊卵巢综合征组卵泡内血小板第4因子(Pf4)和Pf4/IL-8复合体水平显著高于对照组(p=0.004)。PF4的抗通透性作用与减少细胞间隙和拮抗与IL-8的结合有关。结论:本研究首次证实了著名的血管抑制蛋白PF4对人类生殖生物学的病理生理贡献。卵泡内PF4的增加及其抗通透性作用可能影响多囊卵巢综合征卵泡的形成和卵泡的发生。版权所有(C)2018,台湾医学会。爱思唯尔台湾有限责任公司出版。
Background/Purpose: Abnormal folliculogenesis is one of the cardinal presentations of polycystic ovarian syndrome (PCOS) and permeability of follicular wall has been proposed to be involved in the normal follicular growth. However, whether or not there is a change in intrafollicular permeability underlies PCOS is unknown.Methods: This was a tertiary center-based case-control study. From 2014 to 2015, thirteen patients with PCOS who underwent in vitro fertilization-embryo transfer (IVF-ET) were enrolled. Eleven normo-ovulatory patients who underwent IVF-ET due to male factor and/or tubal factor infertility were enrolled as the control group. The influence of ovarian follicular fluid (FF) on endothelial cell permeability was evaluated using a human umbilical vein endothelial cell monolayer permeability assay. The intrafollicular expression profiles of angiogenesis-related proteins were analyzed using a Human Angiogenesis Protein Array Kit.Results: The FF from PCOS patients caused significantly poorer endothelial cell permeability comparing with the effect of FF from the control group (46% +/- 12% vs. 58% +/- 9%, P = 0.023). Among the 55 angiogenesis-related proteins tested, there was a significantly higher level of intrafollicular platelet factor 4 (PF4) and PF4/IL-8 complex in the PCOS group (p = 0.004). The anti-permeability effect of PF4 was related to the decrease in the intercellular gaps and antagonistic binding with IL-8.Conclusion: Our study provides the first evidence of the pathophysiologic contribution of the well-known angiostatic protein, PF4, on human reproductive biology. The increase of the intrafollicular PF4 and its anti-permeability effect might affect the formation of FF and folliculogenesis in PCOS. Copyright (C) 2018, Formosan Medical Association. Published by Elsevier Taiwan LLC.