Placental function in development and disease

The placenta is an organ that clinicians and embryologists would all agree is important for pregnancy success. Unfortunately, however, they too often ignore it when they are exploring causes for embryonic, fetal and perinatal complications. The core function of the placenta is to mediate the transport of nutrients between the maternal and fetal circulation, but it also has critical endocrine functions that alter different maternal physiological systems in order to sustain pregnancy. Both its development and ongoing functions can be dynamically regulated by environmental factors, including nutrient status and tissue oxygenation. In recent years, mainstream attention has begun to shift onto the placenta and it is now becoming clear that placental pathology is associated with several complications in human and animal pregnancies, including embryonic lethality, fetal growth restriction, pre-eclampsia and the high rates of fetal deaths observed after nuclear transfer (cloning).     

胎盘外泌体与妊娠及其并发症的研究进展

细胞产生的细胞外纳米泡称为外泌体（exosome），在组织微环境间传递信息。外泌体是纳米大小的、直径为30～100 nm的微型囊泡，由细胞以可控的方式释放介导多种细胞外和细胞间活动。外泌体的主要功能包括细胞间通讯、免疫调节、细胞外基质周转、干细胞分裂或分化、新生血管形成和细胞废物清除，从而促进机体正常的生理和病理过程。外泌体可以携带多种生物活性因子（蛋白质、RNA和脂质等），广泛存在于外周血、乳汁、尿液、唾液、腹水和羊水等体液中。母体血浆中胎盘来源外泌体的浓度在妊娠期间逐渐增加，在正常胎盘发育和母体免疫耐受中发挥作用；外泌体的生物学变化与妊娠并发症有关，如子痫前期、胎儿生长受限，有助于研发妊娠并发症风险妇女的早期诊断技术、监测治疗反应或可能研发外泌体靶向治疗。综述外泌体与妊娠及其并发症之间的关系进展。     

子痫前期与宫内死胎的相关性研究进展

子痫前期(preeclampsia,PE)是一种动态进展的妊娠相关性疾病,病因具有异质性,是导致孕产妇和胎儿死亡的主要原因之一.正常胎盘的形成是维持胎儿正常生长发育的关键.不正常的胎盘植入被认为是子痫前期的主要发病机制,以胎盘浅着床为中心环节.宫内死胎是一种由多因素导致的严重的妊娠期并发症,60％的宫内死胎与胎盘有关,...     

前置胎盘高危因素的研究进展

我国近年前置胎盘发病率呈明显上升趋势。前置胎盘可引起贫血、产后出血、失血性休克、早产及新生儿窒息等多种并发症,是导致产妇及新生儿死亡的重要原因。了解前置胎盘的高危因素,有助于预防和降低前置胎盘发生风险。笔者拟就目前对前置胎盘高危因素的研究进展进行综述,旨在为降低前置胎盘发病率提供参考依据。     

Non invasive detection of fetal Rh using real-time PCR method

INTRODUCTION: In the last ten years the detection of fetal origin cells and cell free fetal DNA in maternal circulation opened new horizons in non-invasive prenatal diagnosis. The diagnostic possibilities are based on the differences between the maternal and fetal origin DNA. One of the differences could be the Rh blood group and the genetical background. The Rh incompatibility is the most frequent blood group incompatibilities in the clinical practice, which can cause fetal anemia, hydrops and even fetal death. AIMS: The aim of this study was to detect the fetal DNA in maternal circulation, to determine the Rh status of the fetus, and to compare the reliability of the method with the data found in other studies. METHODS: Blood samples and amnionic fluid samples were collected from 30 pregnant women, with Rh negative status, between 11-22 week of gestation presented for genetic amniocentesis at the 1st. Department of Obstetrics and Gynecology, Semmelweis University. After DNA isolation real-time PCR was performed in order to detect the exon 7 of the RhD gene located on the first chromosome (1p36.11.). RESULTS: In 24 cases the PCR reaction gave same result in case of the DNA isolated from plasma and amniotic fluid, but in six cases there was no PCR product of plasma samples and the product was detectable in amniotic fluid samples. The exon 7 was detectable in 25 cases, and there was no product in 5 cases. CONCLUSIONS: The real-time PCR method seems to be an easy and reliable method to determine the fetal Rh blood group. The sensitivity and specificity of the method in this study is in concordance with international data. The use of more than one probe could increase the sensitivity of the method.     

Programming the offspring through altered uteroplacental hemodynamics: how maternal environment impacts uterine and umbilical blood flow in cattle, sheep and pigs

As placental growth and vascularity precedes exponential fetal growth, not only is proper establishment of the placenta important, but also a continual plasticity of placental function throughout gestation. Inadequate maternal environment, such as nutritional plane, has been documented to alter fetal organogenesis and growth, thus leading to improper postnatal growth and performance in many livestock species. The timing and duration of maternal nutritional restriction appears to influence the capillary vascularity, angiogenic profile and vascular function of the placenta in cattle and sheep. In environments where fetal growth and/or fetal organogenesis are compromised, potential therapeutics may augment placental nutrient transport capacity and improve offspring performance. Supplementation of specific nutrients, including protein, as well as hormone supplements, such as indolamines, during times of nutrient restriction may assist placental function. Current use of Doppler ultrasonography has allowed for repeated measurements of uterine and umbilical blood flow including assessment of uteroplacental hemodynamics in cattle, sheep and swine. Moreover, these variables can be monitored in conjugation with placental capacity and fetal growth at specific time points of gestation. Elucidating the consequences of inadequate maternal intake on the continual plasticity of placental function will allow us to determine the proper timing and duration for intervention.     

妊娠期高血压疾病患者母、胎转化生长因子-β1、血管紧张素Ⅱ及血管内皮生长因子表达水平分析

目的比较妊娠期高血压疾病孕妇与正常孕妇外周血、脐带血和胎盘中转化生长因子（TGF）-β1、血管紧张素（Ang）Ⅱ和血管内皮生长因子（VEGF）的表达差异,为探讨妊娠期高血压疾病的发病机制提供临床依据。方法选择2009年1月至2012年12月在成都市妇女儿童中心医院分娩且合并妊娠期高血压疾病,但无其他妊娠合并症的50例孕妇为研究对象,纳入妊娠期高血压疾病组,选择同期在同一家医院分娩的50例正常孕妇纳入对照组。在孕妇分娩时留取胎盘母、子面胎盘组织,母亲静脉血及新生儿脐静脉血,采用酶联免疫吸附测定（ELISA）法测定TGF—β1、AngⅡ和VEGF的表达水平,并进行统计学分析。两组孕妇年龄、孕龄及体质量比较,差异均无统计学意义（P〉0．05）。本研究遵循的程序符合成都市妇女儿童中心医院人体试验委员会制定的伦理学标准,得到该委员会批准,分组征得受试对象知情同意,并与之签署临床研究知情同意书。结果①妊娠期高血压疾病组母亲静脉血、新生儿脐静脉血、胎盘母面及胎盘子面组织中TGF-β1表达水平均较对照组低,而AngⅡ表达水平均较对照组高,且差异均有统计学意义（P〈0．05）;②妊娠期高血压疾病组新生儿脐静脉血、胎盘母面及胎盘子面组织中VEGF表达水平均较对照组低,且差异有统计学意义（P〈0．05）;但两组母亲静脉血VEGF表达水平比较,差异无统计学意义（t=0．639,P〉0．05）。结论TGF-β1、AngⅡ和VEGF表达水平的改变在妊娠期高血压疾病的发生、发展中有重要作用。     

20例孕晚期植入性凶险型前置胎盘的临床分析

目的探讨晚孕期植入性凶险型前置胎盘的临床特点、母婴结局和终止妊娠的治疗方案,以提高对植入性凶险型前置胎盘的认识。方法回顾性分析了福建医科大学省立临床医学院妇产科2010年1月至2012年12月确诊的20例植入性凶险型前置胎盘患者的临床资料,总结植入性凶险型前置胎盘的处理经验。结果20例患者经术前核磁共振、彩超及术中所见明确为植入性凶险型前置胎盘,均以剖宫产结束妊娠。20例均发生产后出血,术中出血量1000～5000mL,平均2600mL。子宫切除12例,膀胱破裂修补3例,3例行介入治疗。早产儿19例。新生儿窒息6例,其中5例轻度窒息,1例重度窒息。结论植入性凶险型前置胎盘对母儿危害大,应提高认识,及时识别,术前应做好充分准备,以减少母婴并发症,介入治疗值得借鉴。     

82例妊娠晚期死胎的临床分析

目的探讨妊娠晚期导致胎死宫内的主要原因,制定预防措施,降低围生儿死亡率。方法对昌吉市人民医院2005～2009年收治的82例死胎病例资料进行回顾性分析。结果死胎的原因顺位依次为妊娠并发症、脐带和胎盘因素。结论加强对育龄妇女的孕期保健知识的宣传,加强高危妊娠的监测,对降低围生期母儿死亡率有重要意义。     

Placental transport function

Placental transport provides a means of supplying nutrients to and removing metabolites from the fetus. Transport is based on substrate exchange and net flux from mother to fetus or vice versa and can be a result of a concentration difference or of unidirectional carrier-mediated transport. Blood flow regulates delivery to and removal from the area of placental exchange, and rapidly crossing compounds are dependent on blood flow for their rate of passage. There are substantial species differences in terms of flow rates normalized for fetal weight and also in terms of vascular arrangement. The barrier can be overcome via paracellular water-filled channels or via a transcellular route. Hydrophilic molecules that are not actively transported diffuse through paracellular channels, and the placentae of rodents and primates are much more permeable than the placenta of the sheep. Many different substrates such as glucose, amino acids, electrolytes and vitamins are transported by carrier systems. Transport proteins are located in the microvillous and basal membranes of the trophoblast. Asymmetry in the kinetics of binding results in differences in influx and efflux at the interface with maternal and fetal blood, allowing directional net flux across the placenta. Immunoglobulins are believed to cross by receptor-mediated endocytosis.     

Docosahexaenoic acid sources for the developing brain during intrauterine life

Docosahexaenoic acid (DHA, 22: 6n-3) and arachidonic acid (AA, 20: 4n-6) provision to the developing fetus, with emphasis towards brain and vascular system growth, is a subject of increasing concern particularly under pathological conditions associated with premature birth or in utero growth restriction following obstruction of the maternal-fetal blood flow. Most of DHA, but also AA accretion under physiological conditions, is maternally dependent and requires adequate maternal nutrition and normally functioning placental-fetal circulation. It has been demonstrated that unlike other fatty acids (FA), DHA is preferentially transported across the placenta into the fetal circulation. The selective transplacental DHA transfer is probably mediated by specific carrier proteins. While some of the latter may be acting in fetal organs, the mechanism(s) for the selective accumulation of DHA in brain is still unknown. The fetal brain and also the fetal liver are capable of producing DHA from linolenic (LnA, 18:3 n-3) acid. How effective this local elongation-desaturation mechanism for DHA provision is and to what degree this route is activated in premature births is not clear. Transfer of DHA via the fetal gastrointestinal tract is an additional route to provide DHA to other fetal organs. As indicated by animal model studies, it holds the potential for DHA supply when the maternal pathway is compromised.     

胎盘辅助性T细胞因子IL-4、IL-6和IFN-γ与子痫前期关系的研究

目的:通过研究辅助性T细胞因子IL-4、IL-6及IFN-γ在子痫前期患者及血压正常的晚期妊娠妇女(NLP)胎盘母体面与胎儿面中的表达规律,探讨其在子痫前期发病过程中的病理生理机制。方法:选取子痫前期和正常妊娠孕妇作为研究组和对照组,应用免疫组化方法对两组胎盘的母体面与胎儿面Th1型细胞因子(IFN-γ)和Th2型细胞因子(IL-4、IL-6)进行标记并通过彩色病理图像分析系统对染色结果进行定量检测并作比较。结果:①胎盘母体面滋养细胞IFN-γ表达的平均光密度在子痫前期轻度组、重度组及正常妊娠组分别为0.2034±0.0148、0.2688±0.0278、0.2075±0.0154,子痫前期重度组与正常妊娠组差异有统计学意义(P0.001);IL-6表达的平均光密度在子痫前期轻度组、重度组及正常妊娠组分别为0.1864±0.0009、0.1579±0.0070、0.1862±0.0127,子痫前期重度组与正常妊娠组差异有统计学意义(P0.001);IL-4表达的平均光密度在子痫前期轻度组、重度组及正常妊娠组分别为0.2026±0.0163、0.1994±0.0163、0.2011±0.0124,3组比较差异均无统计学意义(P0.05)。②胎盘胎儿面滋养细胞IFN-γ、IL-6、IL-4在子痫前期轻度组、重度组及正常妊娠组表达的平均光密度均无统计学差异。③子痫前期重度组滋养细胞IFN-γ、IL-6表达的平均光密度在胎盘母体面与胎儿面比较差异有统计学意义(P0.05);IL-4表达的平均光密度在胎盘母体面与胎儿面比较,无统计学差异(P0.05)。结论:在重度子痫前期孕妇胎盘母体面中表现为免疫杀伤的Th1型细胞因子表达增强,表现为免疫保护的Th2型细胞因子则表达减弱,而在胎盘胎儿面则无上述表现,提示胎盘母体面的Th1/Th2细胞因子失衡可能是导致子痫前期发病的病因之一。     

肿瘤坏死因子-α对胎儿生长受限胎盘Bcl-2、Bax基因表达调节的探讨

目的:探讨胎儿生长受限(FGR)肿瘤坏死因子α(TNF-α)与胎盘组织凋亡相关基因Bcl-2、Bax表达的关系。方法:用放射免疫分析法(RIA)测定25例足月正常体重儿(对照组)和20例FGR组母血、脐血TNF-α浓度;用免疫组化SP法检测胎盘组织中Bcl-2、Bax基因表达;采用图像分析系统进行Bcl-2、Bax阳性细胞率、平均吸光度(A)值测定,量化基因表达。结果:FGR组母血、脐血TNF-α浓度与对照组比较均明显增高(P均<0.05)。FGR组与对照组比较,胎盘Bcl-2阳性细胞率明显降低(P<0.01),A值明显增加(P<0.01);而Bax阳性细胞率明显增高(P<0.01),A值明显降低(P<0.01)。FGR组母血、脐血TNF-α浓度与胎盘Bcl-2阳性细胞率均呈负相关(P均<0.01),与A值均呈正相关(P均<0.01);与Bax表达无关。结论:母血、脐血TNF-α增高是引起FGR的原因之一;FGR组胎盘组织Bcl-2表达下降,Bax表达增高;在FGR中TNF-α可通过对Bcl-2表达的负调节促进胎盘细胞凋亡,抑制胎儿生长发育。     

肿瘤坏死因子受体相关因子6、核转录因子-κB在未足月胎膜早破合并绒毛膜羊膜炎患者外周血和胎盘组织中的表达及意义

目的探讨未足月胎膜早破(PPROM)合并绒毛膜羊膜炎(HCA)患者外周血和胎盘中肿瘤坏死因子受体相关因子6(TRAF6)、核转录因子-κB(NF-κB)表达及意义。方法选取2017年9月-2018年12月于扬州大学临床医院产科住院分娩的74例PPROM孕妇为研究对象。根据胎膜病理结果将PPROM分为对照组(PPROM未合并HCA)和病例组(PPROM合并HCA),采用ELISA和Western blot法检测母血和胎盘中TRAF6和NF-κB的表达水平,比较两种因子在母血、胎盘中的表达和相关性。结果病例组母血、胎盘中TRAF6和NF-κB表达均高于对照组,差异有统计学意义(P<0.05)。病例组TRAF6、NF-κB在母血与胎盘中的表达分别呈正相关;母血、胎盘中TRAF6与NF-κB的表达分别呈正相关。病例组产褥感染率和新生儿肺炎发生率高于对照组。结论TRAF6和NF-κB可能参与PPROM合并HCA的发生。     

An analysis of anemia and pregnancy-related maternal mortality

The relationship of anemia as a risk factor for maternal mortality was analyzed by using cross-sectional, longitudinal and case-control studies because randomized trials were not available for analysis. The following six methods of estimation of mortality risk were adopted: 1) the correlation of maternal mortality rates with maternal anemia prevalence derived from national statistics; 2) the proportion of maternal deaths attributable to anemia; 3) the proportion of anemic women who die; 4) population-attributable risk of maternal mortality due to anemia; 5) adolescence as a risk factor for anemia-related mortality; and 6) causes of anemia associated with maternal mortality. The average estimates for all-cause anemia attributable mortality (both direct and indirect) were 6.37, 7.26 and 3.0% for Africa, Asia and Latin America, respectively. Case fatality rates, mainly for hospital studies, varied from <1% to >50%. The relative risk of mortality associated with moderate anemia (hemoglobin 40-80 g/L) was 1.35 [95% confidence interval (CI): 0.92-2.00] and for severe anemia (<47 g/L) was 3.51 (95% CI: 2.05-6.00). Population-attributable risk estimates can be defended on the basis of the strong association between severe anemia and maternal mortality but not for mild or moderate anemia. In holoendemic malarious areas with a 5% severe anemia prevalence (hemoglobin <70 g/L), it was estimated that in primigravidae, there would be 9 severe-malaria anemia-related deaths and 41 nonmalarial anemia-related deaths (mostly nutritional) per 100,000 live births. The iron deficiency component of these is unknown.     

Intrauterine Transmission of SARS-CoV-2

We documented fetal death associated with intrauterine transmission of severe acute respiratory syndrome coronavirus 2. We found chronic histiocytic intervillositis, maternal and fetal vascular malperfusion, microglial hyperplasia, and lymphocytic infiltrate in muscle in the placenta and fetal tissue. Placenta and umbilical cord blood tested positive for the virus by PCR, confirming transplacental transmission.     

Ex vivo human placenta models: transport of immunoglobulin G and its subclasses

The comparison between fetal and maternal levels of immunoglobulins indicate that the human placenta during pregnancy develops a specific transport mechanism for IgG in the maternal to fetal direction. There are differences for the four subclasses, with preferential transfer of IgG(1) while the slowest transfer is seen for IgG(2).Under in vitro perfusion conditions of human term placenta IgG, when compared to other proteins, showed a significantly higher transfer rate of its subclasses from the maternal to the fetal side, indicating a specific transport mechanism. There is a preferential transfer rate, highest for IgG(1) and lowest for IgG(2), similar to those observed under in vivo conditions. The similarity in transfer of anti-TT-IgG and tetanus antigen, which was observed under in vivo and in vitro conditions, may suggest the transport as antibody-antigen complex.     

Maternal zinc deprivation and interleukin-1 influence metallothionein gene expression and zinc metabolism of rats

The influence of maternal dietary zinc intake and recombinant human interleukin-1 alpha (rhIL-1 alpha) administration on metallothionein gene expression and the distribution of 65Zn were investigated. Pregnant rats were fed diets containing 1, 5, 30 or 180 mg Zn/kg diet in an equalized regime from d 13-20 of gestation. Metallothionein gene expression was examined by Northern blot and dot blot hybridization using combined 60-mer oligonucleotides specific for rat metallothionein-1 and -2 genes. Expression was progressively depressed in the fetal livers and livers and kidneys of dams fed diets marginal (5 mg/kg) and deficient (1 mg/kg) in zinc content. Administration of rhIL-1 alpha increased expression in maternal liver, placenta and in fetal liver of dams fed adequate or deficient diets. Kinetics of intravenously administered 65Zn showed that in response to rhIL-1 alpha, there was a higher uptake by the maternal liver and bone marrow with less 65Zn uptake by bone, intestine and plasma activity compared to controls. No change was observed in 65Zn taken up by the placenta or transferred to the fetus. Alteration of metallothionein gene expression could represent, in part, the mechanism whereby altered effects of zinc metabolism and function are mediated during fetal development.     

Comparison of the effects of dietary glucose versus galactose on porcine feto-placental glucose metabolism

The present study was conducted to determine whether dietary galactose can be used to improve glycogen and lipid accretion in fetal pigs. Pregnant gilts were fed diets containing either 24% glucose (control) or 24% galactose from d 98 to 110 of gestation. Gilts underwent abdominohysterotomy on d 110 of gestation. Slices of fetal subcutaneous adipose tissue and placenta were examined for metabolic capacity for glucose and for galactose utilization. No effects of maternal diet were evident upon glycogen content or enzyme activity of fetal semitendinosus muscle and liver. Maternal dietary galactose had no direct effects upon placental glucose oxidation or use for lipid synthesis. However, galactose supplementation of the incubation medium caused reductions in glucose oxidation (15%) and total lipid synthesis (24%) by the maternal placenta. Maternal dietary galactose caused an increase in total lipid (50%) and fatty acid synthesis (200%) from glucose in fetal subcutaneous adipose tissue; direct supplementation of galactose to the incubation medium had no effect on these parameters. The results of the present study suggest that feeding galactose to the pregnant gilt does not have direct effects upon placental metabolism or fetal glycogen storage. However, these data indicate that use of galactose in the maternal diet can result in an increase in the utilization of glucose for lipogenesis by fetal adipose tissue in swine. This effect is not a direct effect of galactose because transport across the placenta was not apparent.     

Organochlorine compounds in mother and fetus during labor.

Some features of the storage of organochlorine compounds in mother and fetus as assessed during labor are reported in this paper. Organochlorine insecticides (DDT and metabolites, dieldrin, y-BHC, and heptachlor expoxide) and polychlorinated biphenyls were assessed in maternal adipose tissue, maternal blood, fetal blood, maternal uterine muscle, placenta, and amniotic fluid. The concentration of total DDT, y-BHC, and PCBs was greater in extracted lipids of fetal blood than in maternal blood and still higher in the uterine muscle. The concentration of dieldrin and heptachlor expoxide was higher in extracted lipids of fetal blood and placenta than in maternal blood and uterine muscle. The metabolites of DDT were found in different ratios in mother and fetus. The ratios for individual polychlorinated biphenyl compounds were similar for maternal and fetal plasma on the one hand and placenta and uterine muscle on the other. These facts suggest quantitative differences in the ability of these tissues to metabolize and/or store organochlorine compounds. These data emphasize the importance of the maternal organism in protection of the fetus against environmental hazards.