多胺的生殖生物学作用及其研究进展

多胺是一类聚阳离子化合物,包括精胺、亚精胺和腐胺等。哺乳动物体内多胺来源于氨基酸合成或从饮食中摄取,多胺能够清除细胞内过多的活性氧簇(ROS),调节其氧化应激水平。多胺在雄性和雌性的生殖过程和胚胎/胎儿发育中起重要作用。研究发现,多胺参与调节细胞生长和基因表达,且与有丝分裂、减数分裂有关。在雄性,多胺与精子生成相关,并调节精子活性;在雌性,多胺与卵泡发育及排卵有关,且参与调节类固醇激素生成。在体外成熟(IVM)中外源性添加多胺,可有效地减少卵母细胞非整倍体率并且改善其胚胎发育。此外,多胺缺乏会导致胚胎发育停滞。多胺参与胎盘发育以及在胎儿发育过程中母婴的物质交换。综述多胺生物学功能及其对配子发生及胎盘发育的作用。     

足月适于胎龄儿胎盘组织中多胺的性别差异

我们观察了43名足月适于胎龄儿孕38至41周脐血及母血中多胺的变化情况。发现在妊娠后期,脐血内多胺在孕40周达到高峰,母血内多胺在孕39周达到高峰,而胎盘组织内多胺在孕40周处于低谷;且发现男性新生儿胎盘组织内精胺及精眯精胺总量高于女性新生儿。结果表明,胎盘在母体与胎儿-胎盘系统之间的多胺平衡过程中起着重要作用,且不同性别胎儿-胎盘系统有其各自的特点。     

足月适于胎龄儿胎盘组织中多胺的性别差异

我们观察了43名足月适于胎龄儿孕38至41周脐血及母血中多胺的变化情况。发现在妊娠后期．脐血内多胺在孕40周达到高峰．母血内多胺在孕39周达到高峰．而胎盘组织内多胺在孕40周处于低谷；且发现男性新生儿胎盘组织内精胺及精眯精胺总量高于女性新生儿。结果表明。胎盘在母体与胎儿胎盘系统之间的多胺平衡过程中起着重要作用．且不同性别胎儿—胎盘系统有其各自的特点。     

IGFs与胎盘发育及IUGR的相关性

胎儿宫内发育迟缓的围产期死亡率和患病率均较高，近年来内分泌与胎儿宫内发育迟缓发病机制的密切关系已被确认。胰岛素样生长因子在胎儿、胎盘的生长发育中起重要作用，妊娠过程中胎盘是母体与胎儿之间联系的枢纽，尽管对内分泌影响胎盘的中间作用环节知之甚少，但母体及胎儿胰岛素样生长因子能够显著地影响胎盘新陈代谢已被证实。本文意在对其研究进展作简要介绍。     

腐胺在生殖中的安全性研究进展

腐胺是一种二胺,广泛存在于动物体内及食品中,与DNA、RNA、各种配体及膜蛋白作用而发挥一系列生理及病理作用。腐胺在孕期生殖器官中含量增加,与精子发生、精子运动能力、卵泡发育以及排卵密切相关,可以降低高龄雌性卵子非整倍体率,促进卵胞质成熟,增强卵母细胞抗氧化功能,还可以促进早期胎盘功能形成及胚胎、胎儿和婴儿的生长发育。腐胺在体内受到动态平衡调节而处于一定的浓度范围,超过某个浓度或平衡失调将对机体产生一定危害。腐胺虽在动物生殖过程扮演重要角色,但其安全性尚不明确,以致限制其在临床中的应用。本文主要概述腐胺在机体靶器官、生殖过程、胚胎发育中安全性、其药代动力学及遗传毒性和致癌性,为腐胺在辅助生殖和自然受孕的应用提供参考。     

IGFs与胎盘发育及IUGR的相关性

胎儿宫内发育迟缓的围产期死亡率和患病率均较高，近年来内分泌与胎儿宫内发育迟缓发病机制的密切关系已被确认。胰岛素样生长因子在胎儿，胎盘的生长发育中起重要作用，妊娠过程中胎盘是母体与胎儿之间联系的枢纽，尽管对内分泌影响胎盘的中间作用环节知之甚少，但母体及胎儿胰岛素样生长因子能够寺影响胎盘新陈代谢已被证实。     

腐胺在生殖中的安全性研究进展

腐胺是一种二胺,广泛存在于动物体内及食品中,与DNA、RNA、各种配体及膜蛋白作用而发挥一系列生理及病理作用。腐胺在孕期生殖器官中含量增加,与精子发生、精子运动能力、卵泡发育以及排卵密切相关,可以降低高龄雌性卵子非整倍体率,促进卵胞质成熟,增强卵母细胞抗氧化功能,还可以促进早期胎盘功能形成及胚胎、胎儿和婴儿的生长发育。腐胺在体内受到动态平衡调节而处于一定的浓度范围,超过某个浓度或平衡失调将对机体产生一定危害。腐胺虽在动物生殖过程扮演重要角色,但其安全性尚不明确,以致限制其在临床中的应用。本文主要概述腐胺在机体靶器官、生殖过程、胚胎发育中安全性、其药代动力学及遗传毒性和致癌性,为腐胺在辅助生殖和自然受孕的应用提供参考。     

胎盘氨基酸转运体的研究进展

胎盘是母体与胎儿间进行物质交换的器官.胎儿在子宫中发育,依靠胎盘从母体获取营养.氨基酸作为蛋白质的组成成分以及非蛋白物质(例如NO、多胺、核苷酸和神经递质等)合成的重要前体,是一种必需的营养成分,在胎儿的生长发育过程中发挥着至关重要的作用[1].由氨基酸转运体介导的氨基酸跨胎盘转运是供给胎儿能量的重要途径之一,对维持胎儿的存活和胎儿在子宫内的正常生长发育起着关键性的作用.胎盘氨基酸转运体的功能异常可影响胎儿的正常生长发育.近年研究[2]发现:胎盘氨基酸转运体异常可影响胎儿的生长发育,与胎儿宫内发育迟缓等妊娠并发症相关.现对胎盘氨基酸转运体的研究进展作一简要综述.     

血管内皮生长因子参与羊水量调节的作用机制

羊水是维持胎儿生命和发育不可缺少的生活环境,目前尚无理想的方法来准确预测羊水量.羊水量受多种因素的调控,膜内吸收是主要途径,血管内皮生长因子在羊水通过胎儿表面和胎盘到达胎儿血液的过程中起到调节作用,羊膜和绒毛膜中的VEGF基因的高表达与胎儿血液吸收羊水增多相关,可能作用机制是其参与了膜血管增生及体液跨膜转运的调节.     

成纤维细胞生长因子-2与胚胎及胎儿生长发育关系的研究

成纤维细胞生长因子-2(fibroblast growth factors-2,FGF-2)是一种多功能、作用广泛的细胞因子,可以促进细胞有丝分裂的形成。FGF-2参与正常的妊娠过程,调节胎盘的血管形成和舒张,在胎儿发育过程中起重要作用。但关于FGF-2与胎儿生长发育的研究起步较晚,本文主要从FGF-2在胚胎形成及胎儿生长发育方面的机制作一综述。     

Long-term effects of nutritional programming of the embryo and fetus: mechanisms and critical windows

The maternal nutritional and metabolic environment is critical in determining not only reproduction, but also long-term health and viability. In the present review, the effects of maternal nutritional manipulation at defined stages of gestation coinciding with embryogenesis, maximal placental or fetal growth will be discussed. Long-term outcomes from these three developmental windows appear to be very different, with brain and cardiovascular function being most sensitive to influences in the embryonic period, the kidney during placental development and adipose tissue in the fetal phase. In view of the similarities in fetal development, number and maturity at birth, there are close similarities in these outcomes between findings from epidemiological studies in historical human cohorts and nutritional manipulation of large animals, such as sheep. One key nutrient that may modulate the long-term metabolic effects is the supply of glucose from the mother to the fetus, because this is sensitive to both global changes in food intake, maternal glucocorticoid status and an increase in the carbohydrate content of the diet. The extent to which these dietary-induced changes may reflect epigenetic changes remains to be established, especially when considering the very artificial diets used to induce these types of effects. In summary, the maintenance of a balanced and appropriate supply of glucose from the mother to the fetus may be pivotal in ensuring optimal embryonic, placental and fetal growth. Increased or decreased maternal plasma glucose alone, or in conjunction with other macro- or micronutrients, may result in offspring at increased risk of adult diseases.     

Prenatal Choline Supplementation Alters One Carbon Metabolites in a Rat Model of Periconceptional Alcohol Exposure

Prenatal alcohol exposure disturbs fetal and placental growth and can alter DNA methylation (DNAm). Supplementation with the methyl donor choline can increase fetal and placental growth and restore DNAm, suggesting converging effects on one-carbon metabolism (1CM). We investigated the impact of periconceptional ethanol (PCE) exposure and prenatal choline supplementation on 1CM in maternal, placental, and fetal compartments. Female Sprague Dawley rats were given a liquid diet containing 12.5% ethanol (PCE) or 0% ethanol (control) for 4 days before and 4 days after conception. Dams were then placed on chow with different concentrations of choline (1.6 g, 2.6 g, or 7.2 g choline/kg chow). Plasma and tissues were collected in late gestation for the analysis of 1CM components by means of mass spectrometry and real-time PCR. PCE reduced placental components of 1CM, particularly those relating to folate metabolism, resulting in a 3–7.5-fold reduction in the ratio of s-adenosylmethionine:s-adenosylhomocysteine (SAM:SAH) (p < 0.0001). Choline supplementation increased placental 1CM components and the SAM:SAH ratio (3.5–14.5-fold, p < 0.0001). In the maternal and fetal compartments, PCE had little effect, whereas choline increased components of 1CM. This suggests that PCE impairs fetal development via altered placental 1CM, highlighting its role in modulating nutritional inputs to optimize fetal development.     

Environmental regulation of placental phenotype: implications for fetal growth

Environmental conditions during pregnancy determine birthweight, neonatal viability and adult phenotype in human and other animals. In part, these effects may be mediated by the placenta, the principal source of nutrients for fetal development. However, little is known about the environmental regulation of placental phenotype. Generally, placental weight is reduced during suboptimal conditions like maternal malnutrition or hypoxaemia but compensatory adaptations can occur in placental nutrient transport capacity to help maintain fetal growth. In vivo studies show that transplacental glucose and amino acid transfer adapt to the prevailing conditions induced by manipulating maternal calorie intake, dietary composition and hormone exposure. These adaptations are due to changes in placental morphology, metabolism and/or abundance of specific nutrient transporters. This review examines environmental programming of placental phenotype with particular emphasis on placental nutrient transport capacity and its implications for fetal growth, mainly in rodents. It also considers the systemic, cellular and molecular mechanisms involved in signalling environmental cues to the placenta. Ultimately, the ability of the placenta to balance the competing interests of mother and fetus in resource allocation may determine not only the success of pregnancy in producing viable neonates but also the long-term health of the offspring.     

多胺对人及哺乳动物生殖调控作用

多胺(polyamines)是带有正电荷的脂肪族化合物,通过结合DNA、RNA和蛋白质等,参与人及哺乳动物的基因表达调控、细胞信号传导等。多胺可影响下丘脑-垂体-性腺轴激素的分泌,进而影响生殖细胞质量、黄体形成及胚胎发育,对人及哺乳动物生殖过程发挥调控作用,但是其具体作用机制,迄今尚未阐明。笔者拟就多胺的生物合成,人及哺乳动物体内分布及其来源,对精子发生、卵子形成、囊胚着床及发育作用的最新研究进展进行综述,旨在为多胺用于辅助生殖技术(ART)中,改善妊娠结局提供依据。     

胎儿生长受限胎盘组织中细胞凋亡与增殖

目的:通过对胎儿生长受限患者的胎盘组织细胞凋亡和增殖指数的测定,从细胞增殖与凋亡的角度阐述导致胎儿生长受限发生、发展的病理机制。方法:研究对象来自于2007年2月~2009年2月在该院分娩的胎儿生长受限患者31例(FGR组)和正常足月分娩30例(对照组)的胎盘组织。应用TUNEL法及SP法定量测定各种细胞的凋亡指数及增殖指数。结果:两组胎盘各细胞成分均有凋亡发生,细胞凋亡在两组中均以蜕膜细胞和合体滋养细胞为主。胎儿生长受限组〔合体滋养细胞凋亡指数(36.4±9.2)%,蜕膜细胞凋亡指数(40.2±7.5)%〕与对照组相比〔合体滋养细胞凋亡指数(23.3±5.0)%,蜕膜细胞凋亡指数(28.4±8.2)%〕凋亡明显增多,差异有统计学意义(P0.01)。在胎儿生长受限组细胞滋养细胞内有一定量的增殖细胞核抗原表达〔细胞滋养细胞增殖指数(25.1±5.9)%〕,和对照组相比〔细胞滋养细胞增殖指数(17.2±5.8)%〕细胞增殖明显,差异有统计学意义(P0.01)。结论:在胎儿生长受限及正常晚孕的胎盘中均存在凋亡现象。胎儿生长受限患者胎盘中合体滋养细胞及蜕膜细胞凋亡较正常晚孕明显增多,且细胞滋养细胞表现为明显增生,这可能是引起FGR发生、发展的重要病理过程。     

Maternal nutrition and fetal development

Nutrition is the major intrauterine environmental factor that alters expression of the fetal genome and may have lifelong consequences. This phenomenon, termed "fetal programming," has led to the recent theory of "fetal origins of adult disease." Namely, alterations in fetal nutrition and endocrine status may result in developmental adaptations that permanently change the structure, physiology, and metabolism of the offspring, thereby predisposing individuals to metabolic, endocrine, and cardiovascular diseases in adult life. Animal studies show that both maternal undernutrition and overnutrition reduce placental-fetal blood flows and stunt fetal growth. Impaired placental syntheses of nitric oxide (a major vasodilator and angiogenesis factor) and polyamines (key regulators of DNA and protein synthesis) may provide a unified explanation for intrauterine growth retardation in response to the 2 extremes of nutritional problems with the same pregnancy outcome. There is growing evidence that maternal nutritional status can alter the epigenetic state (stable alterations of gene expression through DNA methylation and histone modifications) of the fetal genome. This may provide a molecular mechanism for the impact of maternal nutrition on both fetal programming and genomic imprinting. Promoting optimal nutrition will not only ensure optimal fetal development, but will also reduce the risk of chronic diseases in adults.     

Influences on fetal and placental weights during mid to late gestation in prolific ewes well nourished throughout pregnancy

This study investigated associations between fetal and placental weights from 85 to 130 days gestation in 49 fetuses from 21 ewes of a prolific genotype used as an experimental model of intrauterine growth retardation. The proportion of variation in fetal weight explained by placental weight increased from zero at 85 days to 91% (residual standard deviation (RSD) = 260 g) at 130 days. Overall, stage of pregnancy plus placental weight accounted for 96% of fetal weight variation (RSD = 212 g). Litter size and number of fetuses per uterine horn also influenced individual fetal weights. Gestational age, litter size, placental weight per ewe, and liveweight and condition score of ewes during early to mid gestation (initial LW and CS) explained 99.5% of the variation in fetal weight per ewe (RSD = 236 g). Most variation (86%) in placental weight was explained by stage of pregnancy, litter size, number of placentomes, and initial LW and CS (RSD = 53 g). Placental weight per ewe was influenced by stage of pregnancy, litter size and initial ewe LW and CS (R2 = 0.97; RSD = 89 g). The association of fetal and placental weights with initial ewe LW was positive, and with initial CS was negative. The results show that in the absence of overt nutritional restriction of pregnant ewes, fetal and placental weights are tightly coupled during late gestation and ewe fatness during early pregnancy is inversely related to placental and fetal weights. They demonstrate that placental weight explains most of the variation in fetal weight in the present intrauterine growth retardation model.     

The influence of maternal nutrient restriction in early to mid-pregnancy on placental and fetal development in sheep.

Placental weight is a primary factor determining size at birth in many species. In sheep, placental weight peaks at approximately mid-gestation, with structural remodelling occurring over the second half of pregnancy to meet the increasing nutritional demands of the growing fetus. Numerous factors influence placental growth and development in sheep, and many workers (see Kelly, 1992) have investigated the role of maternal nutrition as a regulator of placental and fetal size. We have studied the effects of feeding ewes approximately 50% of their recommended energy requirements during early to mid-pregnancy on fetal and placental indices measured at mid-gestation (i.e. 80 d) and close to term (i.e. 145 d). Maternal nutrient restriction is associated with a reduction in placental weight at 80 d, but an increase in placental weight at 145 d of gestation, compared with ewes fed adequately in early pregnancy. No significant effect on fetal weight was observed at either 80 or 145 d gestation, although differences in body dimensions and the insulin-like growth factor-1 axis were found in lambs from nutrient-restricted ewes delivered close to term. Maternal nutrition during pregnancy plays a pivotal role in the regulation of fetal and placental development in sheep, and therefore has the potential to influence both short- and longer-term health outcomes.     

77例宫内死胎的相关危险因素分析

目的探讨77例宫内死胎的相关危险因素。方法回顾性分析2004~2013年清华大学第一附属医院收治的宫内死胎产妇的临床病历资料(病例组),并随机选取同期200例单胎活产分娩产妇病历资料(对照组),采用多因素Logistic回归分析宫内死胎的危险因素。结果单因素结果显示,高龄(30岁)、妊娠期高血压疾病、胎盘早剥、前置胎盘、脐带异常、无规律产检、羊水异常、胎儿发育异常的孕妇更易出现宫内死胎(P0.05);不同孕次、产次、流产史、妊娠期糖尿病的孕妇宫内死胎的发生率比较差异无统计学意义(P0.05);不同性别胎儿宫内死胎率比较差异无统计学意义(P0.05)。多因素Logistic回归分析结果显示,高龄(30岁)、妊娠期高血压疾病、胎盘早剥、前置胎盘、脐带异常、羊水异常、胎儿发育异常是宫内死胎的独立危险因素(OR分别为1.675、1.956、1.863、1.985、1.677、1.945、1.954,P均0.05);规律产检是保护因素(OR=0.542,P0.05)。结论高龄(30岁)、妊娠期高血压疾病、胎盘早剥、前置胎盘、脐带异常、羊水异常、胎儿发育异常是宫内死胎的独立危险因素,临床应重点关注高危人群,采取针对性措施进行干预。     

Beneficial effects of dietary fibre supplementation of a high-fat diet on fetal development in rats

The objective of the present study was to investigate the effects of the addition of fibre and the antioxidant N-acetylcysteine (NAC) to fat-rich diets on fetal intrauterine development in rats. A total of eighty virgin female Sprague-Dawley rats were fed a control diet, a high-fat diet (HF), a high-fat and high-fibre diet (HFF) or a high-fat NAC diet until day 19·5 of gestation. Maternal HFF consumption resulted in a significantly higher mean fetal number and placental weight than in the other groups (P < 0·05). The HFF diet significantly abrogated HF-induced decreases in maternal serum and placental superoxide anion and hydroxyl radical scavenging capacities (P < 0·05); partially abrogated HF-induced increases in maternal serum and placental malondialdehyde (MDA) and protein carbonyl concentrations (maternal serum MDA and placental protein carbonyl, P < 0·05); resulted in significantly higher fetal liver total superoxide dismutase (SOD), Cu- and Zn-containing SOD and Mn-containing SOD (Mn-SOD) activities than in the HF group (P < 0·05). Furthermore, mRNA expressions of hypoxia-inducible factor 1-α, thioredoxin 2 and Mn-SOD in fetal liver and Mn-SOD in fetal heart and placental GLUT3 in the HFF group were higher than those in the other groups (P < 0·05). The inclusion of dietary fibre in the HF diet was more effective than NAC supplementation in maintaining maternal serum and placental superoxide anion and hydroxyl radical scavenging capacities close to those of the control. These results suggest that maternal fibre intake during pregnancy is beneficial for fetal intrauterine development possibly through the improvement of maternal, placental and fetal antioxidant capacities and placental nutrient transfer capacity.