Major tissue remodelling occurs in hormone responsive tissues of the female genital tract, at ovulation and during gestation, involving proteolysis and inflammation. Disorders of tissue remodelling events are associated with infertility in women with luteinized unruptured follicle syndrome and with gestational pathologies as preeclampsia. Ovulation impairment is an important factor of infertility and a major concern in reproductive medicine. The gonadotrophin discharge inducing ovulation triggers proteolytic activities involved in the breakdown of the follicular wall and elicits an acute inflammatory reaction in the ovary. Tight control of these reactions is required to allow successful ovulation while avoiding excessive tissue damage. Anticoagulant heparan sulfate proteoglycans (aHSPG), like heparin, possess a pentasaccharide sequence which binds and activates antithrombin III. These proteoglycans are produced by endothelial cells and are thought to endow the vascular wall with antithrombotic properties. aHSPG are also present in the reproductive tract; in the ovary they are strongly expressed in granulosa cells of preovulatory follicles and they are co-localised with serine protease inhibitors involved in the control of proteolytic activities at ovulation. The presence of aHSPG in the oviduct, in the uterus and in human follicular fluid, suggests that they could play additional distal roles in gestation. The females exhibited impaired ovarian function as well as intrauterine growth restriction linked to delayed placenta development. In these mice, the placenta is challenged by inflammation at mid-gestation, occasionally resulting in miscarriage and maternal death. Collectively, these observations suggest that aHSPG are involved in the control of inflammatory events occurring during tissue remodelling in hormone-responsive tissues. Further studies are needed to identify the inflammation mediators involved in this process.

译文

主要组织重塑发生在女性生殖道的激素反应性组织中,在排卵和妊娠期间,涉及蛋白水解和炎症。组织重塑事件的障碍与黄体化未破裂卵泡综合征和妊娠病理为先兆子痫的女性的不育有关。排卵障碍是不孕症的重要因素,也是生殖医学的主要关注点。促性腺激素释放诱导排卵会触发参与卵泡壁破裂的蛋白水解活动,并在卵巢中引起急性炎症反应。需要严格控制这些反应,以使排卵成功,同时避免过度的组织损伤。抗凝血硫酸乙酰肝素蛋白聚糖 (aHSPG) 与肝素一样,具有结合并激活抗凝血酶III的五糖序列。这些蛋白聚糖是由内皮细胞产生的,被认为赋予血管壁抗血栓形成特性。aHSPG也存在于生殖道中; 在卵巢中,它们在排卵前卵泡的颗粒细胞中强烈表达,并且与参与控制排卵时蛋白水解活性的丝氨酸蛋白酶抑制剂共定位。输卵管,子宫和人卵泡液中aHSPG的存在表明它们可能在妊娠中起其他远端作用。女性表现出卵巢功能受损以及与胎盘发育延迟有关的宫内生长受限。在这些小鼠中,胎盘在妊娠中期受到炎症的挑战,偶尔会导致流产和孕产妇死亡。总的来说,这些观察结果表明,aHSPG参与了激素反应性组织中组织重塑过程中发生的炎症事件的控制。需要进一步的研究来确定参与此过程的炎症介质。

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