妊娠期母体／胎儿皮质醇的代谢及调节

皮质醇是妊娠期母体代谢与胎儿发育代谢不可缺少的物质。母体内与胎体内的皮质醇浓度梯度提示,胎盘是阻止母体皮质醇到达胎儿的屏障,11β-羟基类固醇脱氢酶（11β—HSD）在这个屏障中起主导作用。在妊娠不同阶段,皮质醇代谢与调节存在差异。母体的皮质醇能在妊娠中晚期通过胎盘。多种因素会影响11β—HSD的活性,进而影响皮质醇在母体与胎儿问的代谢调节。     

胎盘11β-羟基类固醇脱氢酶和促肾上腺皮质激素释放激素与胎儿发育和分娩发动的关系

胎盘是妊娠期间重要的内分泌器官,胎盘除合成一些经典的类固醇激素和蛋白质类激素外,还分泌下丘脑激素,如促肾上腺皮质激素释放激素(corticotropin-releasing hormone, CRH)和存在大量的糖皮质激素的代谢酶--11β-羟基类固醇脱氢酶(11β-hydroxysteroid dehydrogenase,11β-HSD).近来的研究提示,胎盘分泌的CRH可能起分娩发动的生物钟作用,它决定着分娩何时发动[1,2];胎盘表达的11β-HSD调节着糖皮质激素对胎盘和胎膜的作用;胎盘的11β-HSD还是妊娠期母体和胎儿之间的糖皮质激素的屏障,防止过多的糖皮质激素导致胎儿生长受限和编码一些与疾病相关的基因[3,4].本文将近年来胎盘CRH和11β-HSD与胎儿发育和分娩发动的关系的研究进展综述如下.     

胎盘11β-HSD2在子代成年后高血压病发生中的作用

胎盘是介导母体与胎儿血氧、营养物质及代谢物传递的一个重要器官。根据DOHaD理论,胎儿宫内生长环境的变化会影响胎儿的发育,导致子代成年后罹患高血压病等风险增加。大量研究显示,胎盘11β-羟类固醇脱氢酶(11β-HSD2)能有效地将母体糖皮质激素在通往胎儿的过程中灭活,使胎儿免受糖皮质暴露。因此,胎盘11β-HSD2水平降低会引起胎儿宫内糖皮质激素过度暴露,导致子代成年后发生高血压病的风险显著增高。本文拟阐述胎盘11β-HSD2在胎盘中的结构和功能及其在子代成年后高血压病发生机制中的作用。深入了解胎盘11β-HSD2的变化与子代高血压病之间的关系对研究胎盘功能及代谢、产前诊断、胎源性成人疾病防治等具有重要意义。     

胎盘11β-HSD表达调节与糖皮质激素治疗

糖皮质激索(GC)可对胎儿生长发育产生复杂的效应.胎盘11β-羟基类固醇脱氢酶(11β-HSD)作为糖皮质激素代谢限速酶调节母胎间经胎盘转运糖皮质激素量,其分为11β-HSD1和11β-HSD2两种亚型.11β-HSD在不同物种胎盘之间表达具有种属差异,同一物种的胎盘不同部位表达也不完全一样.胎盘部位11β-HSD表达还随孕龄发生改变.胎盘部位11β-HSD表达调节机制复杂,尚未完全明确.雌激素、孕激素、某些金属离子、缺氧和细胞因子等参与11β-HSD表达调节.产前不同物种给予糖皮质激素后,胎盘11β-HSD表达具有差异,主要表现为灵长类动物胎盘11β-HSD2表达上调,而绵羊等动物11β-HSD2表达下调.胎盘11β-HSD与糖皮质激素的关系研究,将有助于阐明11β-HSD在糖皮质激素治疗中所起的作用以及指导临床用药.     

胎盘11β-HSD表达调节与糖皮质激素治疗

糖皮质激素（GC）可对胎儿生长发育产生复杂的效应。胎盘11β-羟基类固醇脱氢酶（11β-HSD）作为糖皮质激素代谢限速酶调节母胎间经胎盘转运糖皮质激素量,其分为11β-HSD1和11β-HSD2两种亚型。11β-HSD在不同物种胎盘之间表达具有种属差异,同一物种的胎盘不同部位表达也不完全一样。胎盘部位11β-HSD表达还随孕龄发生改变。胎盘部位11β-HSD表达调节机制复杂,尚未完全明确。雌激素、孕激素、某些金属离子、缺氧和细胞因子等参与11β-HSD表达调节。产前不同物种给予糖皮质激素后,胎盘11β-HSD表达具有差异,主要表现为灵长类动物胎盘11β-HSD2表达上调,而绵羊等动物11β-HSD2表达下调。胎盘11β-HSD与糖皮质激素的关系研究,将有助于阐明11β-HSD在糖皮质激素治疗中所起的作用以及指导临床用药。     

重度子痫前期孕妇脂氧素A4及11β羟基类固醇脱氢酶2的表达及意义

目的:检测重度子痫前期孕妇外周血中脂氧素A4(LXA4)水平以及胎盘组织中11β羟基类固醇脱氢酶2(11β-HSD2)表达,探讨LXA4和11β-HSD2参与重度子痫前期发生的机制。方法:选择在本院产前检查并分娩的妊娠妇女共45例,其中正常妊娠组20例,重度子痫前期组25例。ELISA法测定孕妇外周血血浆中LXA4水平;酶化学发光分析法检测孕妇血清中游离皮质醇浓度;免疫组织化学染色法检测胎盘组织11β-HSD2蛋白表达;实时荧光定量RT-PCR法测定胎盘组织11β-HSD2 mRNA的表达;分析LXA4与11β-HSD2蛋白或mRNA、皮质醇与平均动脉压之间的相关性。结果:重度子痫前期组与正常妊娠组相比,LXA4水平明显降低(P<0.05),皮质醇浓度虽有升高,但无显著性差异(P>0.05);胎盘组织中11β-HSD2蛋白及mRNA表达均显著低于正常妊娠组(P<0.05);两组孕妇的LXA4水平与11β-HSD2蛋白表达量、LXA4水平与11β-HSD2 mRNA表达量、皮质醇与平均动脉压均无相关性(P均>0.05)。结论:LXA4和11β-HSD2参与重度子痫前期的发生。     

地塞米松对人类胎盘糖皮质激素代谢酶11β-HSD2的调节

目的:研究地塞米松对人类胎盘糖皮质激素受体前代谢酶11β-HSD2活性的调节作用,探讨产前应用地塞米松对妊娠和胎儿的影响,为临床防治早产和合理应用糖皮质激素提供理论依据。方法:利用改良的Kliman法分离提纯胎盘滋养细胞,原代培养3天后药物处理,用放射性酶活性结合薄层层析法(TLC)测定地塞米松对11β-HSD2氧化酶活性的调节作用。结果:体外实验条件下,培养的胎盘滋养层细胞具有11β-HSD2氧化酶活性,且与时间呈依赖关系。地塞米松作用于细胞4h、8h后,胎盘合体滋养细胞11β-HSD2的氧化酶活性明显降低,但孵育24h后,酶活性无明显变化。结论:地塞米松可显著降低胎盘合体滋养细胞11β-HSD2的氧化酶活性,可能是地塞米松、对胎儿有不良影响的重要机制之一,因此产前应用地塞米松必须慎重。     

妊娠病理状态下胎儿血氧代谢的变化及其临床管理

正成人氧代谢通过肺部直接与外界进行氧气交换,而胎儿血氧代谢通过胎盘屏障实现氧气交换。胎儿氧供依赖于充足的母体含氧量、子宫-胎盘及胎盘-胎儿血流以及富氧血的正常分布。胎盘血流、母体-胎儿间的氧分压差以及氧含量(母体的携氧能力)、胎盘血氧弥散面面积及弥散膜的厚度是胎儿氧代谢的决定因素。影响母体携氧及胎盘-胎儿血氧交换等的妊娠病理状况均可影响胎儿血氧代谢。1胎儿氧代谢生理生理条件下,胎儿静脉血(富氧血)氧分压不     

早孕期绒毛和蜕膜的组织化学观察

111例正常早孕人工流产的胎盘组织作绒毛蜕膜组织化学观察。蜕膜细胞,富于糖元,碱性磷酸酶多呈阳性或弱阳性,酸性磷酸酶多数阴性或弱阳性,少数阳性。3β-HSD弱阳性,蜕膜腺体弯曲呈锯齿状,腺体壁呈扇形,有时细胞向内突出如鞋钉状,腔内充满分泌物,糖元强阳性,对维持早期妊娠是一个重要营养条件。早期妊娠绒毛具有完整两层滋养层,即合体滋养层及细胞滋养层,60天后则细胞滋养层逐步消失,绒毛大小不等,胎儿血管扩大并移向绒毛表面,从而使胎儿-母体胎盘屏障变薄,有利于胎儿-母体的物质交换,是适应胚胎发育的一个重要条件。早孕期绒毛组织化学检查显示绒毛两层细胞糖元和碱性磷酸酶活性都很强,反映代谢机能活跃,细胞滋养层胞浆酸性磷酸酶活性60—90天逐渐加强,这应与此时期细胞滋养层退化有关。3β-HSD 在甾体生物合成过程中起重要作用,绒毛滋养层细胞3β-HSD皆为阳性,表明具有甾体生物合成机能。着床、早孕过程中,绒毛、蜕膜是母体-胚胎直接接触和相互联系的两种组织,从计划生育角度,在发展抗着床、抗早孕药物研究工作中,对于蜕膜、绒毛形态和机能的研究应当受到重视。     

一氧化氮和血管内皮生长因子对胎盘功能及胎儿生长发育的调控

胎盘是联系胎儿与母体的重要器官,是胚胎与母体组织的结合体。胎盘通过调节胎儿与母体之间物质交换、合成多种激素和酶类,影响胎儿的生长发育和代谢。已发现胎盘的重量及大小与胎儿体重呈正相关［１］。慢性胎盘功能不良常导致胎儿宫内生长迟缓（ＩＵＧＲ）,甚至胎死宫...     

Anonymous and non-anonymous gamete and embryo donations: pros and cons

Consequences of legal restrictions concerning gamete and embryo donation have been increasingly discussed during the last three decades, partly dependent upon the fact that assisted reproductive technologies have opened up new medico-technical possibilities. In the present communication we want to elucidate some of the problems and consequences of a Swedish law from 1985 requiring that all sperm donors should be non-anonymous. A similar law was passed in 2003 for oocyte donation. Such legal restrictions do not seem to be in the interest of the infertile couple who, to a large extent, seek treatment abroad where the laws are more liberal or non-restrictive (reproductive tourism). Whether or not the Swedish law is in the best interest for the offspring remains to be seen.     

Adiposity and Endometriosis Severity and Typology

Study ObjectivePrior research has collectively shown that endometriosis is inversely related to women's adiposity. The aim of this study was to assess whether this inverse relationship holds true by disease severity and typology.DesignCross-sectional study among women with no prior diagnosis of endometriosis.SettingFourteen clinical centers in Salt Lake City, UT, and San Francisco, CA.PatientsA total of 495 women (of which 473 were analyzed), aged 18–44 years, were enrolled in the operative cohort of the Endometriosis, Natural History, Diagnosis, and Outcomes (ENDO) Study.InterventionsGynecologic laparoscopy/laparotomy regardless of clinical indication.Measurements and Main ResultsParticipants underwent anthropometric assessments, body composition measurements, and evaluations of body fat distribution ratios before surgery. Surgeons completed a standardized operative report immediately after surgery to capture revised American Society for Reproductive Medicine staging (I–IV) and typology of disease (superficial endometriosis [SE], ovarian endometrioma [OE], and deep infiltrating endometriosis [DIE]). Linear mixed models, taking into account within-clinical-center correlation, were used to generate least square means (95% confidence intervals) to assess differences in adiposity measures by endometriosis stage (no endometriosis, I–IV) and typology (no endometriosis, SE, DIE, OE, OE + DIE) adjusting for age, race/ethnicity, and parity. Although most confidence intervals were wide and overlapping, 3 general impressions emerged: (1) women with incident endometriosis had the lowest anthropometric/body composition indicators compared with those without incident endometriosis, (2) women with stage I or IV endometriosis had lower indicators compared with women with stage II or III, and (3) women with OE and/or DIE tended to have the lowest indicators, whereas women with SE had the highest indicators.ConclusionOur research highlights that the relationship between women's adiposity and endometriosis severity and typology may be more complicated than prior research indicates.     

Blood lead and cadmium and birth weight among sub-arctic and arctic populations of Norway and Russia

BACKGROUND: Delivering women and their newborns in the Kola Peninsula of Russia and the neighboring arctic area of Norway were studied to explore relationships between maternal cadmium and lead status and birth weight as a pregnancy outcome. METHODS: Life-style information, maternal blood and cord blood specimens were collected from 50 consecutive mother-infant pairs from hospital delivery departments in three Russian and three Norwegian communities. Pregnancy outcomes were verified by consulting medical records. Lead and cadmium were determined in the blood samples by electrothermal atomic absorption spectrometry. RESULTS: The median blood-cadmium concentration for the Russian mothers was 2.2 nmol/L (n = 148) versus 1.8 nmol/L in the Norwegian group (n = 114, p = 0.55). A weak association was observed between maternal cadmium and amount smoked (r = 0.30, p<0.001); no correlation was found between maternal blood cadmium and birth weight. The corresponding maternal lead values were 0.14 (Russia) and 0.06 micromol/L (Norway), p<0.001. The latter lead concentration constitutes one of the lowest adult population values reported to date. Maternal and cord blood lead levels were strongly correlated (r = 0.88, p<0.001). In a multivariate linear regression model, maternal blood lead was recognized as a negative explanatory variable (p<0.05) for birth weight and child's body mass index (BMIC), with or without adjustment for gestational age. A similar association was suggested by ANOVA-analysis of maternal blood lead by quartiles. CONCLUSION: Maternal blood-lead level as an environmental factor is an apparent predictor of low birth weight and BMIC. It reduced substantially the contribution of a country factor in explaining the observed differences in birth weight.     

Reproductive and menstrual factors and risk of peritoneal and ovarian endometriosis

OBJECTIVE: Between 1987 and 1989 data were collected to evaluate risk factors for pelvic endometriosis. DESIGN: A case-control study was conducted on 241 cases with laparoscopically or laparotomically confirmed peritoneal or ovarian endometriosis consecutively admitted to three teaching hospitals in Northern Italy. The control group consisted of 437 women admitted to hospitals for acute conditions covering similar catchment areas. RESULTS: Compared with nulliparous women, the risk of endometriosis decreased with increasing number of births: the point estimates were 0.4 and 0.3, respectively, for those with one and two or more births (X2(1) trend = 50.3, P less than 0.001). No relation emerged with age at first birth and spontaneous miscarriages. Relative to women whose menarche occurred at age 11 or younger, the risk of endometriosis was slightly lower in those who experienced later menarche, but the trend in risk was not significant. Women with irregular menstrual cycles showed a lower frequency of the disease (relative risk, 0.3; 95% confidence interval, 0.2 to 0.5). The role of various factors was largely similar for different disease locations (ovary, peritoneum, and both) and indication for diagnostic surgery (sterility, pelvic pain, and other reasons). CONCLUSIONS: This study found that parity and irregular/long menses lower the risk of endometriosis. These findings were similar in different subgroups of disease location and indication for surgery, giving strong evidence of the consistency of the general results.