基质金属蛋白酶在女性生殖系统中的作用

基质金属蛋白酶（matrix metalloproteinase,MMPs）是一类蛋白水解酶,可高效调节和控制细胞外基质（extra cellular matrix,ECM）的逆转和平衡。MMPs参与多种生物学过程,例如胚胎发育、血管新生、软骨重建、肿瘤发生和角膜修复等[1]。由于女性生殖系统的结构和功能不断发生周期性的变化,其ECM水解和重建与MMPs的关系更密切。本文就其对生殖系统作用作一综述。     

单克隆抗体阻断Le~Y寡糖对小鼠胚泡细胞外基质与基质金属蛋白酶的影响

目的:探讨着床前阶段表达的LeY寡糖对小鼠胚泡细胞外基质(ECM)与基质金属蛋白酶(MMPs)表达的影响。方法:应用半定量RT-PCR及免疫印迹法观察体外培养的着床前表面LeY寡糖被封闭的胚泡ECM主要成分纤维粘连蛋白(FN)、层粘连蛋白(LN)和其水解酶类MMP-2,MMP-9的表达和分泌水平的变化。结果:体外培养表面被封闭胚泡6 h,其FN及LN的分泌明显升高(P<0.01),但随着培养时间延长,其增高水平有下降趋势,而其基因的转录变化不明显。在同一时期内,胚泡MMP-2、MMP-9的分泌明显被抑制,其抑制程度随培养时间延长减弱,其基因表达也被抑制,与其分泌水平的变化趋势一致。结论:LeY寡糖抗原被封闭使MMPs的分泌和基因表达被抑制的同时,FN、LN的分泌增加,提示可能与LeY寡糖封闭引起MMPs的活性下降,使其底物FN、LN分解减少,从而引起含量增加有关。     

基质金属蛋白酶与子宫内膜癌关系的研究

子宫内膜癌是女性生殖道常见的恶性肿瘤之一，倍受妇产科学界关注。目前已经发现金属基质蛋白酶（MMPs）在许多肿瘤的发生和发展中起重要作用，但对子宫内膜癌的研究甚少。本研究拟通过检测MMPs在正常子宫内膜、子宫内膜癌前病变，子宫内膜癌组织中的表达情况，探讨基质金属蛋白酶（MMPs）及钙粘蛋白（E—CAD）在子宫内膜癌发病方面的价值。     

多囊卵巢综合征患者IVF治疗中超促排卵方案的对比研究

目的:探讨不同的超排卵方案对多囊卵巢综合征(PCOS)患者实施IVF-ET治疗过程的影响。方法:回顾分析行IVF治疗、长方案超促排卵的PCOS患者134个移植周期,比较分析不同超促排卵方案、促排卵药物的IVF-ET结局。结果:①递增方案组(n=7,6)总Gn使用量明显大于递减方案组(n=74)、Coasting方案组(n=16)和恒量方案组(n=18)(P<0.05)。②后期添加hMG组(n=61)总Gn使用量明显大于单用FSH组(n=73)(P<0.05),着床率也明显降低(P<0.05),但临床妊娠率无显著性差异(P=0.064);③普丽康组(n=43)与果纳芬+hMG组(n=22)及普丽康+hMG组(n=39)相比,总Gn使用量明显减少(P<0.05),而与果纳芬组(n=30)间无统计学差异;普丽康组与普丽康+hMG组相比,获卵数明显增加(P<0.05)。结论:PCOS患者的长方案超排卵方案中,递增方案增加了Gn使用总量而临床妊娠率有偏低的趋势;添加hMG不能提高着床率和临床妊娠率;单纯普丽康超排卵有减少总Gn使用量,增加获卵数的趋势。     

基质金属蛋白酶及其组织抑制剂在卵巢浆液性肿瘤中的表达及意义

基质金属蛋白酶 (ｍａｔｒｉｘｍｅｔａｌｌｏｐｒｏｔｅｉｎａｓｅｓ,ＭＭＰｓ)家族成员中的ＭＭＰ 2、ＭＭＰ 9降解基底膜的主要成分Ⅳ型胶原 ,而基底膜是肿瘤侵袭的第一道细胞外屏障 ,ＭＭＰ 2、ＭＭＰ 9的过度表达与人类许多恶性肿瘤的侵袭、转移密切相关[1 ,2 ] 。它们的功能活性受其组织抑制剂 (ｔｉｓｓｕｅｉｎｈｉｂｉｔｏｒｓｏｆｍｅｔａｌｌｏｐｒｏｔｅｉｎａｓｅｓ,ＴＩＭＰｓ)的抑制。本研究用免疫组织化学 (组化 )的方法研究ＭＭＰ 2、ＭＭＰ 9和ＴＩＭＰｓ家族中的ＴＩＭＰ 1在卵巢良性、交界性、恶性浆液性肿瘤中的定位及…     

MMP-2、TIMP-1和TIMP-2在胚胎停育绒毛和蜕膜组织中的表达

目的:探讨MMP-2,TIMP-1和TIMP-2与胚胎停育的关系。方法:选取胚胎停止发育妇女为病例组,另设同期正常早孕自愿要求流产的妇女为对照组,分别留取其绒毛和蜕膜组织标本,采用半定量RT-PCR法对标本MMP-2,TIMP-1和TIMP-2 mRNA转录水平进行分析。结果:在绒毛标本中,MMP-2和TIMP-1 mRNA在病例组中表达水平显著低于对照组(P<0.01);而TIMP-2mRNA表达水平组间差异无统计学意义(P>0.05)。在蜕膜标本中,病例组TIMP-1 mRNA的表达水平显著低于对照组(P<0.01)。而MMP-2和TIMP-2 mRNA的表达水平组间差异无统计学意义(P>0.05)。结论:MMP-2,TIMP-1和TIMP-2的差异表达可能参与了胚胎停育的发生发展。     

基质金属蛋白酶在卵巢癌侵袭转移中的研究进展

侵袭和转移是卵巢癌患者死亡的直接原因.基质金属蛋白酶(MMPs)通过降解细胞外基质(ECM)在卵巢癌侵袭转移中发挥重要作用,深入研究MMPs降解ECM的机制,选择针对MMPs的抑制物来治疗卵巢癌的转移是一个很有希望的目标.     

基质金属蛋白酶在卵巢癌侵袭转移中的研究进展

侵袭和转移是卵巢癌患者死亡的直接原因,基质金属蛋白酶（MMPs）通过降解细胞外基质（ECM）在卵巢癌侵袭转移中发挥重要作用,深入研究MMPs降解ECM的机制,选择针对MMPs的抑制物来治疗卵巢癌转移是一个很有希望的目标。     

基质金属蛋白酶与早产的关系

由于早产机制未完全阐明。故早产发生率及早产儿发病率和死亡率一直无明显下降．感染和胎膜早破是早产的主要原因，近来研究认为感染和胎膜早破引起的早产和妊娠妇女体内基质金属蛋白酶（MMPs）的含量变化有关，这两种情况引起的早产发生前，母体血、尿及羊水中的MMPs含量将升高。从而降解妊娠组织的细胞外基质（ECM），引起胎膜破裂及宫颈成熟扩张，而导致早产，且测定妊娠妇女体内MMPs的含量变化可进行早产预测以及应用其抑制剂在动物实验中可降低早产的发生率。     

基质金属蛋白酶与子宫内膜

基质金属蛋白酶是一类依赖Zn2+和Ca2+的可降解细胞外基质的蛋白水解酶类.它在子宫内膜的表达,对内膜重塑、月经发生及胚胎植入起重要的作用,本文就其性质和在子宫内膜中的分布、调节及作用作一综述.     

New insights into the pathophysiology of endometriosis

Endometriosis is a fascinating and complex disease resulting from a dysregulation between exfoliated menstrual endometrium and the intra-abdominal environment. Increased concentrations of activated pelvic macrophages and lymphocytes and elevated levels of specific cytokines and growth factors in the peritoneal fluid support this hypothesis. The precise roles of these soluble factors are currently unknown, but we propose that a complex interplay of these locally produced cytokines, growth factors, steroids and eicosanoids modulates the growth and inflammatory behavior of ectopic endometrial implants via neovascularization. The enhanced secretion of local proangiogenic proteins by endometriosis lesions and associated immune cells (and the concomitant reduction of antiangiogenic principles) promotes the recruitment of capillaries toward the growing lesions. Ultimately, a cascade of effects on the peritoneal microenvironment results in implant proliferation and invasion. Future therapeutic strategies to target these angiogenic stimuli have the potential to block the vascular pathogenesis of endometriosis. This article gives an overview of the different factors involved in the development, growth and progression of endometriosis.     

New insights into the genetics of preeclampsia

Preeclampsia is familial. Pedigree analyses suggest that one or more common alleles may act as "preeclampsia susceptibility genes." The authors speculate that genes involved in blood pressure control, volume regulation, placental health, vascular disease, and vascular remodeling, underlie familial susceptibility to preeclampsia. Several candidate genes have been examined. These data suggest that a common mutation in the angiotensinogen promoter, A(-6), leads to elevated expression of this gene and pleiotropic effects, including abnormal spiral artery remodeling and failed hypervolemia of pregnancy. The factor V Leiden mutation, which predisposes women to thromboembolic disorders during pregnancy, has been implicated as another preeclampsia susceptibility gene. New insights into the genetics of preeclampsia will contribute to the understanding of this disease and should ultimately lead to improved diagnosis and treatment.     

New insights into the management of post-hemorrhagic hydrocephalus

During the last decade, an increasing number of studies have been conducted to improve the outcome of post-hemorrhagic hydrocephalus (PHH), a complication of severe intraventricular hemorrhage (IVH) in preterm infants. Two randomized controlled trials have shown that treatment should be initiated prior to the onset of clinical symptoms. Ventricular access devices and subgaleal shunts are used as temporary neurosurgical interventions whereas ventriculoperitoneal shunts are performed for infants with progressive hydrocephalus. Recently, techniques such as neuro-endoscopic lavage have also been introduced to eliminate toxic blood products and debris from the cerebral ventricles and have shown promise in early clinical studies. The objective of this review is to provide an update on management of PHVD and PHH in the preterm infant.     

New insights into the pelvic organ support framework

Objective

It is important to understand the underlying mechanisms of the physiological framework of the pelvic organ support system to develop more effective interventions. Developing more successful interventions for restoration of defects of the pelvic floor will lead to symptomatic improvement of pelvic floor prolapse and stress incontinence disorders. The purpose of the current study was to investigate the physiological framework related to the pelvic organ support system and propose the underlying mechanisms of pelvic organ support based on the anatomical findings.

Study design

Ten female soft embalmed cadavers were dissected after a colorectal hands-on workshop to visualize components of the pelvic organ support system.

Results

The puborectalis attached at the superior pubic ramus above the arcus tendineus fasciae pelvis. The anterior half of the iliococcygeus originated at the level of the arcus tendineus fasciae pelvis but descended from the arcus tendineus fasciae pelvis before it reached the ischial spine. The fibrous visceral sheath of the endopelvic fascia covered both the bladder and the upper vagina and bound these structures together. The levator ani muscle was separated into a horizontal and a vertical part at the medial attachment of the fibrous visceral sheath. A well-circumscribed adipose cushion pillow, in the ischioanal fossa and its anterior recess, supported the horizontal part of the levator ani muscle and pressed the vertical part against the pelvic viscera. Perivascular sheaths and pelvic nerve plexuses were reinforced by condensed endopelvic fascia, they suspended the pelvic organs posterolaterally.

Conclusion

The pelvic organ support framework consists of two mechanical structures: (1) the supporting system of the levator ani muscle, the arcus tendineus fasciae pelvis and the adipose cushion pillow, and (2) the suspension system of the neurovascular structures and the associated endopelvic fascia condensation.     

New insights into human pre-implantation metabolism in vivo and in vitro

The metabolism of pre-implantation embryos is far from being understood. In human embryos, the two major obstacles are the scarcity of material, for obvious ethical reasons, and complete absence of a relevant in vivo control model. Over-extrapolation from animal species to human systems adds to the complexity of the problem. Removal of some metabolites from media has been proposed, such as glucose and essential amino acids, on the basis of their pseudo “toxicity”. In contrast, addition of some compounds such as growth factors has been proposed in order to decrease apoptosis, which is a natural physiologic process. These suggestions reflect the absence of global knowledge, and in consequence mask reality. Some aspects of metabolism have been ignored, such as lipid metabolism. Others are seriously underestimated, such as oxidative stress and its relationship to imprinting/methylation, of paramount importance for genetic regulation and chromosomal stability. It has become increasingly obvious that more studies are essential, especially in view of the major extension of ART activities worldwide.     

New insights into possible factors contributing to male subfertility

Male subfertility contributes significantly to fertility problems in couples. Although semen analysis may identify abnormalities in sperm numbers, morphology and/or motility that might contribute to subfertility, in other instances the semen parameters may appear to be normal, but the spermatozoa might be dysfunctional. A number of endogenous and exogenous factors have now been identified that can significantly affect sperm function in vitro and it is possible that they may have similar effects in vivo . Some endogenous factors maintain the spermatozoa in a non-fertilizing state, to avoid them 'burning out' and losing fertility before they reach an oocyte, while others stimulate spermatozoa to become fertile and then hold them in a state of readiness to fertilize. Exogenous environmental molecules, referred to as xenobiotics, have been shown to continuously stimulate spermatozoa so that they become fertile quickly, but then 'burn out'. Defects relating to the endogenous molecules could result in spermatozoa either never becoming fertile or becoming fertile too quickly and so losing fertilizing potential. By understanding the mechanisms involved in promoting sperm fertilizing ability, it may be possible to develop new therapeutic treatments to overcome such defects. (Reprod Med Biol 2005; 4 : 45–53)     

New insights into the pathophysiology of sickle cell disease-associated priapism

IntroductionPriapism is defined as an erectile disorder, in which erection persists uncontrollably without sexual purpose. The precise mechanisms involved in the development of sickle cell disease‐associated priapism are ill defined.AimTo summarize the recent developments that increase our understanding of the molecular mechanisms of priapism.MethodsThis article reviews the literature (Medline search 2000–2010) that relates the key molecular signaling pathways that contribute to the development of priapism associated with sickle‐cell disease. It focuses on basic science investigations using multiple animal models.Main Outcome MeasuresThe reader will be informed of the most current research regarding the role of endothelial nitric oxide synthase, phosphodiesterase type 5 (PDE5), adenosine, RhoA/Rho‐kinase (ROCK), and opiorphins in the pathophysiology of priapism.ResultsNew concepts in the field of priapism research suggest that priapism often results from altered vascular homeostatic actions in the penis and is associated with deficient erection control mechanisms on a molecular level. A leading proposal in this regard is the notion of aberrant signaling of the endothelium‐derived nitric oxide and PDE5 signal transduction pathway in the penis. Additionally, dysfunctional regulatory control of signal transduction systems which interact with this pathway such as adenosine and RhoA/Rho‐kinase may contribute to the development of priapism. Recent investigations of opiorphins also demonstrate a role in regulating corporal smooth muscle tone and thereby dysregulation of erection physiology in priapism. These advances have paved the way for understanding this disorder as having a molecular pathogenesis.ConclusionsAs the science underlying priapism further emerges, increasingly effective therapeutics for sickle cell disease‐associated priapism is certain to follow. Bivalacqua TJ, Musicki B, Kutlu O, and Burnett AL. New insights into the pathophysiology of sickle cell disease‐associated priapism. J Sex Med 2012;9:79–87.     

New insights into fatigue and health-related quality of life after delivery

BACKGROUND: A delivery has a major impact on the health-related quality of life (HRQoL) of the new mother, especially on fatigue. A common complication during delivery that might have a relationship with maternal morbidity is blood loss. The objectives were to investigate fatigue and HRQoL in women after vaginal delivery (VD), elective caesarean section (CS) and emergency CS, and its relationship with postpartum hemoglobin (Hb) levels during the first 6 weeks postpartum. METHODS: Some 141 patients (71 after VD, 36 after elective CS and 34 after emergency CS) completed the HRQoL questionnaires MFI and EQ-5D between 12 and 24 h after VD and 24-48 h after CS (t=0). At 1, 3 and 6 weeks postpartum these questionnaires were repeated, together with the SF36. RESULTS: Patients after VD had higher mean physical HRQoL scores than after CS. The average period to reach full physical recovery was 3 weeks after VD, 6 weeks after elective CS, and >6 weeks after emergency CS. Mean mental HRQoL scores of the study groups were similar or even better compared to reference values. The significant correlation between Hb level and mean physical HRQoL scores found at t=0 had disappeared at 1 week postpartum. CONCLUSIONS: Results of this study provided insights into the natural course of fatigue and HRQoL postpartum. Important differences in fatigue and HRQoL scores were observed between the 3 modes of delivery. These HRQoL measures can be used in future clinical trials to assess the effects of interventions postpartum.