导致母胎免疫耐受机制的研究进展

胎儿携带二分之一父方基因和二分之一母方基因，因而可看作是移入母体内的半异体移植物，成功妊娠中胎儿之所以不被母体排斥，是由于妊娠期母体存在免疫耐受机制，其包括独特的HLA表面分子、补体调节蛋白的特异表达、系统性及局部的免疫改变等。该文就导致母胎免疫耐受的各种因素作一综述。     

白细胞介素-35的生物学活性及其在妊娠免疫耐受中的作用机制

妊娠是对母体免疫系统的一项重大挑战。从生殖免疫学观点来看,妊娠是一种成功的半同种移植,胚胎的成功种植依靠母体及胎儿的共同作用[1],其有赖于妊娠妇女对妊娠半同种抗原所表现的一种免疫耐受,而正常的妊娠免疫耐受涉及诸多因素的相互影响和相互制约,一旦这种母-胎免疫调节失衡,母体对胚胎产生排斥.     

吲哚胺2，3双加氧酶与妊娠免疫耐受

吲哚胺2,3-双加氧酶(IDO)是一种免疫调节酶,是肝脏以外唯一可催化色氨酸分子中吲哚环氧化裂解、沿犬尿酸途径进行分解代谢的限速酶,介导IDO+细胞对T淋巴细胞增殖抑制效应。IDO是妊娠免疫耐受的重要机制之一,参与调节母胎免疫关系,保护胎儿免受母体T细胞攻击,IDO表达异常或者活性失调导致妊娠免疫耐受失调,与多种妊娠相关疾病的发生与发展关系密切。     

吲哚胺2,3双加氧酶与妊娠免疫耐受

吲哚胺2,3-双加氧酶(IDO)是一种免疫调节酶,是肝脏以外唯一可催化色氨酸分子中吲哚环氧化裂解、沿犬尿酸途径进行分解代谢的限速酶,介导IDO+细胞对T淋巴细胞增殖抑制效应.IDO是妊娠免疫耐受的重要机制之一,参与调节母胎免疫关系,保护胎儿免受母体T细胞攻击,IDO表达异常或者活性失调导致妊娠免疫耐受失调,与多种妊娠相关疾病的发生与发展关系密切.     

妊娠免疫耐受机制的研究进展

<正>自Owen于1945年首先报道了在胚胎期接触同种异型抗原所致免疫耐受的现象,在此基础上1953年Medawar提出胎儿作为异体抗原的载体,为何能在母体子宫内存在、发育而不被排斥,免疫学界虽已经从多方面对免疫耐受机理进行研究,已取得很大进展,但至今妊娠期间诱导产生免疫耐受的详细机制尚未阐明。究竟妊娠的免疫耐受机制如何,笔者对     

人类白细胞抗原G与妊娠

妊娠期,母体免疫系统通过多种途径对带有父源性人类白细胞抗原(HLA)的胎儿形成免疫耐受.其中特异性表达在胎盘绒毛外细胞滋养层上(直接连接子宫蜕膜层与母体血液、子宫组织)的人类白细胞抗原G(HLA-G)在诱导母胎免疫耐受及维持正常妊娠中发挥重要作用,HLA-G通过多种途径诱导母胎耐受.对HLA-G的结构特点、受体、功能及其表达特点进行如下综述.     

母体肠道菌群失调及其子宫内转移对母胎影响的研究进展

子宫内有细菌存在,并且可能对胎儿产生影响。母胎间菌群转移的具体作用机制迄今尚未阐明。胎儿肠道菌群的主要来源除了母体血液、胎盘和羊水外,母体肠道亦可能是胎儿肠道菌群的主要来源之一。母体肠道菌群通过血液等途径转移至子宫内,再经过胎盘血液循环和羊水等途径转移至胎儿肠道和免疫系统。母体孕期肠道菌群的结构与数量,可对孕妇及其子代肥胖、神经系统发育异常和血压调节产生影响。随着基因测序技术的发展,有助于更深入探讨母体肠道菌群失调及其子宫内转移与母胎疾病之间的关系,为胎源性疾病的预防和干预提供理论依据。笔者拟就母体肠道菌群失调及其子宫内转移对母胎影响的研究进展进行综述。     

人类白细胞抗原G与妊娠

妊娠期，母体免疫系统通过多种途径对带有父源性人类白细胞抗原（HLA）的胎儿形成免疫耐受。其中特异性表达在胎盘绒毛外细胞滋养层上（直接连接子宫蜕膜层与母体血液、子宫组织）的人类白细胞抗原G（HLA-G）在诱导母胎免疫耐受及维持正常妊娠中发挥重要作用，HLA-G通过多种途径诱导母胎耐受。对HLA-G的结构特点、受体、功能及其表达特点进行如下综述。     

母体血清学与胎儿游离mRNA检测在产前筛查21三体综合征效能比较

目的:分析母体血清学检测与母体血胎儿游离mRNA检测在21三体综合征产前筛查中的价值。方法:回顾性收集2016年4月—2017年10月本院产前筛查确诊胎儿为21三体综合征的单胎孕妇30例(综合征组)和胎儿正常的单胎孕妇60例(健康组)临床资料,孕妇产前均行母体血清学检测和母体血游离胎儿mRNA检测,分析两种方法在21三体综合征产前筛查效能。结果:综合征组血清甲胎蛋白和游离雌三醇Mom值均低于健康组,绒毛膜促性腺激素Mom值高于健康组(均P0.05);两组均检出HPL基因、β-hCG基因、TFPI2基因和PLAC4基因,两组各基因检出率无差异(P0.05),综合征组HPL基因、β-hCG基因、PLAC4基因mRNA表达量均大于健康组(P0.05),TFPI2基因mRNA表达量与健康组无差异(P0.05)。母体血胎儿游离mRNA检测和外周血胎儿DNA无创筛查21三体综合征的AUC值(0.894、0.927)无差异(P0.05)但均大于母体血清学检测(0.815)(P0.05)。结论:母体血清学检测和母体血胎儿游离mRNA检测在21三体综合征产前筛查中均具有重要价值,但后者筛查效能更高。     

妊娠晚期母体外周血与胎儿脐血淋巴细胞凋亡的对比研究

目的:比较妊娠晚期母体外周血与胎儿脐血间淋巴细胞凋亡及其调控基因的表达,探讨妊娠期母体与胎儿在免疫功能方面的差异。方法:采用流式细胞技术分析ICP及正常妊娠妇女外周血及脐血间淋巴细胞凋亡率;以免疫细胞化学染色技术检测两组孕妇外周血及脐血间淋巴细胞上Fas、FasL、Bcl-2的蛋白表达。结果:正常妊娠组脐血淋巴细胞凋亡率显著高于外周血(P<0.05),脐血淋巴细胞上Fas、FasL的表达显著低于母体外周血淋巴细胞(P<0.05),而Bcl-2在两者间无显著性差异;ICP组脐血淋巴细胞凋亡率亦明显高于外周血(P<0.05),脐血淋巴细胞上Fas、Bcl-2的表达显著低于母体外周血淋巴细胞(P<0.05),FasL在两者间无显著性差异。结论:妊娠晚期外周血与脐血间淋巴细胞的凋亡及其调控基因的表达存在差异,而这种差异可能在维持妊娠期免疫耐受的稳定性及移植物抗宿主的排斥反应方面有重要的作用。     

Nutrient partitioning during pregnancy: adverse gestational outcome in overnourished adolescent dams

Appropriate nutrient partitioning between the maternal body and gravid uterus is essential for optimum fetal growth and neonatal survival, and in adult sheep nutrient partitioning during pregnancy generally favours the conceptus at the expense of the dam. However, recent studies using an overnourished adolescent sheep model demonstrate that the hierarchy of nutrient partitioning during pregnancy can be dramatically altered in young growing females. Overnourishing the adolescent dams to promote rapid maternal growth throughout pregnancy results in a major restriction in placental mass and leads to a significant decrease in birth weight relative to moderately-fed adolescents of equivalent gynaecological age. High maternal feed intakes are also associated with an increased incidence of non-infectious spontaneous abortion, a reduction in gestation length and colostrum production, and a higher incidence of neonatal mortality. The present paper examines the putative role of a variety of endocrine regulators of nutrient partitioning in this unusual model system, where the dam is overnourished while the stunted placenta restricts nutrient supply to the fetus. The central role of nutritionally-mediated alterations in placental growth and development in setting the subsequent pattern of nutrient partitioning between the maternal body, placenta and fetus is examined, and critical periods of sensitivity to alterations in maternal nutritional status are defined. Finally, the consequences of this form of inappropriate nutrient partitioning on the growth and development of the fetus and neonate are described with particular emphasis on the reproductive axis.     

Effect of placental function on fatty acid requirements during pregnancy

The fetus has an absolute requirement for the n-3/n-6 fatty acids and docosahexaenoic acid (22:6 n-3; DHA) in particular is essential for the development of the brain and retina. Most of the fat deposition in the fetus occurs in the last 10 weeks of pregnancy. The likely rate of DHA utilisation during late pregnancy cannot be met from dietary sources alone in a significant proportion of mothers. De novo synthesis makes up some of the shortfall but the available evidence suggests that the maternal adipose tissue makes a significant contribution to placental transport to the fetus. The placenta plays a crucial role in mobilising the maternal adipose tissue and actively concentrating and channelling the important n-3/n-6 fatty acids to the fetus via multiple mechanisms including selective uptake by the syncytiotrophoblast, intracellular metabolic channelling, and selective export to the fetal circulation. These mechanisms protect the fetus against low long-chain polyunsaturated fatty acid (LCPUFA) intakes in the last trimester of pregnancy and have the effect of reducing the maternal dietary requirement for preformed DHA at this time. As a result of these adaptations, small changes in the composition of the habitual maternal diet before pregnancy are likely to be more effective in improving LCPUFA delivery to the fetus than large dietary changes in late pregnancy. There is little evidence that DHA intake/status in the second half of pregnancy affects visual and cognitive function in the offspring, but more studies are needed, particularly in children born to vegetarian and vegan and mothers who may have very low intakes of DHA.     

Iodine deficiency in pregnancy: the effect on neurodevelopment in the child

Iodine is an integral part of the thyroid hormones, thyroxine (T(4)) and tri-iodothyronine (T(3)), necessary for normal growth and development. An adequate supply of cerebral T(3), generated in the fetal brain from maternal free T(4) (fT(4)), is needed by the fetus for thyroid hormone dependent neurodevelopment, which begins in the second half of the first trimester of pregnancy. Around the beginning of the second trimester the fetal thyroid also begins to produce hormones but the reserves of the fetal gland are low, thus maternal thyroid hormones contribute to total fetal thyroid hormone concentrations until birth. In order for pregnant women to produce enough thyroid hormones to meet both her own and her baby's requirements, a 50% increase in iodine intake is recommended. A lack of iodine in the diet may result in the mother becoming iodine deficient, and subsequently the fetus. In iodine deficiency, hypothyroxinemia (i.e., low maternal fT(4)) results in damage to the developing brain, which is further aggravated by hypothyroidism in the fetus. The most serious consequence of iodine deficiency is cretinism, characterised by profound mental retardation. There is unequivocal evidence that severe iodine deficiency in pregnancy impairs brain development in the child. However, only two intervention trials have assessed neurodevelopment in children of moderately iodine deficient mothers finding improved neurodevelopment in children of mothers supplemented earlier rather than later in pregnancy; both studies were not randomised and were uncontrolled. Thus, there is a need for well-designed trials to determine the effect of iodine supplementation in moderate to mildly iodine deficient pregnant women on neurodevelopment in the child.     

表观遗传学DNA甲基化与非创伤性产前诊断

表观遗传学研究与DNA序列改变无关,仅发生表现型改变的过程,DNA甲基化是表观遗传学最具特征的标志之一,DNA甲基化技术的进展将其应用领域扩大到非创伤性产前诊断。甲基化特异性PCR可快速、灵敏地根据胎儿和母亲之间DNA甲基化的差异从母血浆中检测胎儿DNA。     

Intergenerational exchange and perinatal risks: a note on interpretation of generational recurrence risks

Population-based data that cover reproductive health outcomes across two complete generations have recently become available in the Nordic countries. Such data enable estimation of recurrence risks from one generation to the next of different conditions such as birth defects or pre-eclampsia. Risks related to a singleton pregnancy involve the contribution of three individuals: the mother, the father and the fetus. A paternal contribution is mainly through the father's contribution of half of the alleles of the fetus. A maternal contribution may occur in three fundamentally different ways. First, the mother provides half of the genomic alleles to the fetus, with contribution of paternal alleles completing the whole genome. Second, the mother provides the fetal environment and possible susceptibility to complications during pregnancy which she may have inherited from her mother. Finally, she provides the fetal mitochondria. Because of these different contributions, recurrence from mother to offspring is fundamentally different from recurrence from father to offspring. How recurrence risks reflect and shape the underlying contributions to overall perinatal risk is illustrated through a review of published data from Norway on gestational age, pre-eclampsia and birth defects.     

Iron endowment at birth: maternal iron status and other influences

The iron endowment at birth depends, in large part, on the newborn's birth weight and gestational age. These are determined by many factors, some of which are maternal characteristics, including the following: maternal iron stores at her own birth and during her own early life, maternal growth and development, maternal age at conception, intergenesic intervals, maternal body characteristics and iron status at conception and during early pregnancy, gestational body weight gain, and iron status throughout gestation, particularly at conception and early pregnancy, and gestational body weight gain. Although less studied, paternal influences on the initiation and progression of pregnancy and on maternal environmental exposures are also important. Even though tools for the quantitative evaluation of women's iron status are very well developed, the quantitative estimation of body iron in the newborn and young infant remains a challenge. This article describes the crucial role played by the placenta in protecting the embryo and the fetus. In addition, neonatal health, particularly early in pregnancy, is briefly addressed, as are some important aspects of antenatal nutritional interventions that include iron.     

手术室对娩出胎盘的管理

胎盘是胚胎与母体的结合体,它作为母体与胎儿间进行物质交换的器官。其实胎盘本身并不可以为胎儿提供所需要的营养物质,在母体内需要进行母胎间物质交换。所以母体存在的病毒也会影响到胎儿的健康发育,比如一些严重的风疹、肝炎以及艾滋病等。可见胎盘中的营养成分与病毒因素并存,所以在手术室必须加强娩出胎盘的管理。本文主要为了使胎盘的管理更加规范,不断地健全相关管理措施,具体的方案如下文所述。     

母亲DHA摄入与胎儿、婴儿DHA营养状况及发育的关系

二十二碳六烯酸 (DHA)对胎儿、婴儿发育的重要生理作用已经引起了营养学界的广泛关注。孕妇和乳母作为胎儿、婴儿营养的主要提供者 ,其DHA营养状况对胎、婴儿DHA营养和发育具有重要影响。在孕期和 (或 )哺乳期补充DHA的母亲 ,其婴儿具有较高的血DHA水平和较好的体格、视力和智力发育水平。本文对国内外有关母亲DHA摄入与胎儿、婴儿DHA营养状况及发育关系的近期研究资料进行了综述。     

Breed differences in fetal and placental development and feto-maternal amino acid status following nutrient restriction during early and mid pregnancy in Scottish Blackface and Suffolk sheep

This study assessed the effect of feeding 0.75 energy requirements between Days 1 and 90 of pregnancy on placental development and feto-placental amino acid status on Day 125 of pregnancy in Scottish Blackface and Suffolk ewes carrying a single fetus. Such moderate nutrient restriction did not affect placental size, placentome number or the distribution of placentome types. Although fetal weight was unaffected by maternal nutrition, fetuses carried by nutrient restricted mothers had relatively lighter brains and gastrocnemius muscles. Suffolk fetuses were heavier and longer with a greater abdominal circumference, relatively lighter brains, hearts and kidneys, but heavier spleens, livers and gastrocnemius muscles than Blackface fetuses. Total placentome weight was greater in Suffolk than Blackface ewes. Ewe breed had a greater effect on amino acid concentrations than nutrition. Ratios of maternal to fetal amino acid concentrations were greater in Suffolk ewes than Blackface ewes, particularly for some essential amino acids. The heavier liver and muscles in Suffolk fetuses may suggest increased amino acid transport across the Suffolk placenta in the absence of breed differences in gross placental efficiency. These data provide evidence of differences in nutrient handling and partitioning between the maternal body and the fetus in the two breeds studied.     

Distribution of radioactivity from 14C-formaldehyde in pregnant mice and their fetuses.

The distribution of 14C after the administration of 14C-formaldehyde was studied in pregnant mice by a whole body low temperature autoradiographic technique. The concentrations of formaldehyde and its metabolites in maternal and fetal blood and tissues were determined in unsectioned tissues by liquid scintillation spectrophotometry. The binding of 14C from 14C-formaldehyde to cells and DNA in maternal and fetal mouse liver was also measured. Radioactivity of 14C deriving from 14C-formaldehyde was found immediately after injection, and showed strong accumulation and retention three hours after injection. The organs that had high concentrations at all studied survival intervals were maternal liver, intestinal mucosa, bone marrow, kidneys, and salivary glands. Considerable amounts of radioactivity were found in the fetuses at six hours after injection, and the concentrations were almost the same as in the maternal tissues. The elimination of 14C-formaldehyde and metabolites from the placenta and fetus occurred more slowly than from maternal tissue.