Origin and fate of fetuin-containing neurons in the developing neocortex of the fetal sheep

Summary The development of the neocortex has previously been extensively studied in carnivores (cat and ferret), rodents (rat and mouse) and primates (monkey and human). In these species, it has been shown that the initial population of cells migrating from the ventricular zone forms the primordial plexiform layer. This is subsequently split into marginal zone and subplate zone by the insertion of later-migrating cells into the primordial plexiform layer, to form the cortical plate proper. Many of the cells derived from the split primordial plexiform layer are transient. The neurons of the subplate zone are found in the deeper part of layer VI, and white matter deep to layer VI in the more mature cortex; most of these neurons disappear by adulthood. [³H]-thymidine labelling in the present study has shown a similar pattern of neocortical development in Artiodactyla (sheep). In addition it has been shown that the previously described staining of subplate and cortical plate cells for the fetal protein fetuin indicates that fetuin is a useful marker for a proportion of this transient population of neurons and defines its extent in neocortical development more clearly. Dividing cells were labelled by a single intra-amniotic injection of [³H]-thymidine at E26 to E35 (birth is at E150). The brains were subsequently examined at E40 or E80 for [³H]-thymidine labelling and fetuin staining by a combination of autoradiography and immunocytochemistry. The earliest generated neocortical cells detected in this study (E26) were found in two layers by E40, the outer marginal zone and inner subplate zone. Neurons of the marginal zone were generated up to E28; those of the early subplate zone were generated up to E31. The cortical plate proper was generated by cells born on E32 and later. This sequence is similar to that described in other species, especially the cat. A proportion of the early-generated neurons in the marginal zone, subplate zone and early cortical plate stained for fetuin. By E80 these earliest-generated, fetuin-positive cells were found in the white matter deep to the forming neocortical layers and in layer VI. In adult brains no fetuin-positive neurons could be identified in the neocortex, and neurons had almost entirely disappeared from the white matter. The fetal glycoprotein fetuin seems to be specifically associated with a population of cells that has the same developmental history as the transient marginal zone and subplate neurons described in other species. However, the distribution of fetuin-containing neurons is more extensive and includes some of the neurons within the cortical plate itself. Thus in addition to being a marker for a proportion of the transient marginal zone and subplate cells, the presence of fetuin in subplate and cortical plate neurons, given the trophic properties attributed to fetuin, may indicate its involvement in early stages of synaptogenesis and connectivity in the developing neocortex.     

细胞外基质受体α-Dystroglycan影响胸腺细胞分化发育的可能机制

目的研究细胞外基质受体alpha-Dystroglycan(α-DG)对胸腺细胞分化的影响及机制。方法摘取15日胚龄鼠胸腺小叶进行体外器官培养。将α-DG抗体、对照抗体或培养液滴加在胸腺小叶上。FACS(Fluorescence-activated cell sorting)分析胸腺细胞表面分子CD4、CD8、CD95和CD69等的表达。结果α-DG中和抗体能明显抑制胸腺细胞分化，显示胸腺双阴性细胞比例从对照组的26．5％增高到实验组的71．6％，双阳性细胞和CD8单阳性细胞比例则显著下降，分别从39．8％和20．7％下降到7．5％和6．8％，CD4单阳性细胞比例则无明显变化；同时胸腺细胞数目明显减少；CD95、CD69的表达水平随α-DG中和抗体的持续存在呈现显著升高。结论α-DG通过参与胸腺细胞的活化和凋亡活动影响胸腺细胞的发育。     

胚胎小鼠肝脏Sca-1+细胞横向分化的研究

目的:研究和探索胚胎小鼠肝脏细胞的横向分化潜能。方法:将2×10³ C57BL/6j雄性胚胎小鼠的肝脏Sca-1⁺细胞从尾静脉注射到受致死性γ射线(10 Gy, ⁶⁰Co)全身照射的同种成年雌性小鼠体内;于移植后2个月, 用荧光原位杂交和免疫组织化学技术, 检测雄性胚胎小鼠肝脏Sca-1⁺细胞在雌性受体小鼠肾脏和脑组织内的分化情况。结果:在雌性受体小鼠的肾脏和脑组织内, 分别检测到Y染色体阳性的供体来源的肾小管上皮组织细胞样和神经组织细胞样的细胞, 其细胞表型分别为RCA⁺/CD^-₄₅F^-_4/80和NueN⁺/CD^-₄₅F^-_4/80。结论:胚胎小鼠肝脏Sca-1⁺细胞具有向肾脏和脑组织细胞横向分化的能力。     

Changes of enzyme activities in ovine fetal fluids and maternal blood serum with gestational age

Our objectives were threefold: (1) to assess the activities of tissue enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and creatine kinase (CK) in the fetal fluids (amniotic and allantoic) collected from the gravid sheep uteri obtained from the abattoir and also in the maternal blood serum at various stages of pregnancy, (2) to compare the enzyme activities of fetal fluids relative to the maternal serum, and (3) to compare the enzyme activities in serum of pregnant ewes to nonpregnant ones. The stages of gestation, viz., stage I (30–60 days), stage II (61–90 days), and stage III (91–120 days) were identified based on the crown anus length of the fetus. As the gestational ages increased, AST significantly (p < 0.01) increased in the amniotic fluid and maternal blood serum but decreased in allantoic fluid; ALT had no changes in fetal fluids and the maternal blood serum; ALP decreased significantly (p < 0.01) in allantoic fluid but had no changes in the amniotic fluid and maternal serum; LDH increased significantly (p < 0.01) in amniotic and allantoic fluids but decreased in maternal serum; CK decreased significantly (p < 0.01) in fetal fluids and maternal serum. The enzyme activities were significantly higher in maternal sera than fetal fluids but were successively less in allantoic and amniotic fluids (p < 0.01). The activity of enzymes in maternal sera of pregnant and nonpregnant ewes were nearly the same. Except for LDH and CK, the greatest activities were found in the maternal serum in stage I and for AST in stage III of pregnancy (p < 0.01). These findings may have appreciable diagnostic significance in prenatal detection of disease status in both the dam and the fetus.     

Changes in thymic export of L-selectin+ γδ and αβ T cells during fetal and postnatal development

We have used the technique of in situ intrathymic injection of fluorescein isothiocyanate to examine L-selectin expression on γδ and αβ T cells immediately after emigrating from the thymus of fetal and postnatal animals. We found that the percentage of L-selectin⁺ thymocytes exported per day decreased by half after birth and that the export of T cells from the thymus does not rely on expression of the peripheral lymph node homing receptor, L-selectin. Analysis of L-selectin on emigrant and mature T cell subsets revealed a remarkable heterogeneity of expression, both in terms of the numbers of cells expressing this molecule as well as the level of expression. γδ T cells, reportedly not having a propensity for homing to lymph nodes, not only contained the highest proportion of L-selectin⁺ cells, but also expressed far more of this molecule than either CD4⁺CD8^? or CD4^?CD8⁺ αβ T cells. Furthermore, those emigrant T cells expressing L-selectin are somewhat immature in their expression of this molecule. Subsequent maturation resulted in up-regulation of L-selectin on mature peripheral blood T cells, maturation that was clearly independent of extrinsic antigen. This antigen-independent post-thymic maturation appeared to occur as part of the normal progression from immature thymocyte to mature peripheral T cell in both fetal and postnatal animals.     

根据孕妇参数预测胎儿体重的神经网络方法

本文采用反向传播神经网络算法,根据孕妇身高、体重、宫高及腹围预测胎儿体重。建立了一个预测胎儿体重的网络模型,讨论了确定网络拓扑结构的方法。采用该方法预测了１４０例胎儿体重,预测符合率高达８５％,相对误≤１０％者占预测总数的９４．２８％。采用神经网络分析输入对于输出的贡献的结果表明孕妇宫高对于胎儿体重影响最大。     

Chemical Characterization of Macrophage Cytotoxicity Factor,Macrophage Migration Inhibitory Factor,T-Helper Cell-Replacing Factor and Colony-Stimulating Factor from Culture Supernatants of Concanavalin A-Stimulated Murine Spleen Cells

Supernatants from Concanavalin A-stimulated murine spleen cells were subjected to hydrophobic interaction chromatography on phenyl-Sepharose. Macrophage cytotoxicity factor (MCF), macrophage migration inhibitory factor (MIF), T-helper cell-replacing factor (TRF) and colony-stimulating factor (CSF) were bound at high ionic strength and were released stepwise at low ionic strength. CSF thus could be separated from MCF, MIF and TRF and the bulk of other proteins. Chromatography of pools containing MCF, MIF and TRF on Sephadex did not lead to a separation of the three activities which were all found in a molecular weight range of 25.000-55.000. Isoelectric focusing of these pools in pH range from 4 to 9 gave two peaks for MCF at pH 8.2 and 7.2, whereas MIF activity focused from pH 4.5 to 5.5. TRF activity was found in a single sharp peak at pH 5.3. The results demonstrate that the four biological activities can be distinguished on a chemical basis and are accessible for purification and chemical characterization.     

Ultrasonic vocalizations and maternal-infant interactions in a rat model of fetal alcohol syndrome

When isolated from their dams and littermates, rat pups emit ultrasonic vocalizations to elicit attention and retrieval from their dams. This study examined the effects of perinatal alcohol exposure on ultrasonic vocalizations and maternal-infant interactions. Alcohol was administered throughout gestation to the dams and during the early postnatal period to the pups. Control groups consisted of a nontreated control and an intubated, pair-fed control. Ultrasonic vocalizations were measured on postnatal day (PD) 5 under varying conditions of isolation. Maternal behaviors were examined on PD2, 4, 6, 8, and 10. Maternal behaviors were not significantly affected by prior alcohol administration to either the dams or the pups. However, ethanol-exposed rat pups vocalized more on PD5 than controls regardless of condition. The heightened vocalization response of the ethanol-exposed pups might be an underlying factor in the persistent effects of perinatal ethanol exposure on social behavior.     

Microproteins in amniotic fluid as an index of changes in fetal renal function during development

Protein content and protein composition were studied in amniotic fluid obtained from 171 healthy pregnant women between the 16th and 38th week of gestation, using microgradient gel electrophoresis to separate proteins according to their molecular size into albumin (68 KD), proteins of low molecular weight (LMW proteins, <68 KD), and proteins of high molecular weight (HMW proteins, >68 KD). Additionally -1-microglobulin (-1-MG, 33 KD) and -2-microglobulin (-2-MG, 11,8 KD) were analysed as micromolecular marker proteins. Concentrations of LMW proteins were 0.15–0.22 g/l, of -1-MG 28.4–34.5 mg/l, and of -2-MG 7.2–11.6 mg/l during the second trimester of gestation, and thereafter decreased progressively to 0.03 g/l, 14.1 mg/l and 2.4 mg/l respectively near term. The same developmental trends were confirmed by calculating the protein/creatinine ratios in amniotic fluid. The concentrations of LMW proteins found in the first postnatal urine of 73 healthy infants born prematurely or at term were similar to those in amniotic fluid of corresponding fetal age. Concentrations of albumin and HMW proteins in postnatal urine were about 5% and 15% respectively when compared with amniotic fluid concentrations. No strong correlation existed between gestational age and either of the analysed proteins which would allow accurate assessment of fetal maturation by protein analysis in amniotic fluid. It is concluded that fetal urinary excretion is the major determinant of the microprotein content of amniotic fluid. Microproteins seem to reflect an increasing tubular reabsorption capacity, which accelerates rapidly after the second trimester of gestation.     

Impact of maternal pre-pregnancy body mass index on maternal,fetal and neonatal adverse outcomes in the worldwide populations: A systematic review and meta-analysis

ObjectiveSystematic review and meta-analysis conducted to investigate the effect of stratified pre-pregnancy maternal body mass index on twenty maternal and fetal/neonatal adverse outcomes.MethodsPubMed, Google Scholar, Medline, Embase, Web of Science databases were searched from inception till July 11, 2020. Cohort studies were included. The pooled odds ratio with 95% confidence interval was reported considering the random effect and the quality effect model. The sub-group analysis and meta-regression were conducted for BMI cut-offs, geographical region, source of BMI, and sample size.ResultsOverall, 86 studies representing 20,328,777 pregnant women were included in this meta-analysis. Our study reveals that overweight and obese mothers are at increased odds of cesarean delivery, elective cesarean delivery, emergency cesarean delivery, gestational diabetes, gestational hypertension, induction of labor, postpartum hemorrhage, pre-eclampsia, pre-term premature rupture of membrane, and the fetuses/neonates of overweight and obese mothers are at increased risk of admission in the newborn intensive care unit, APGAR scores less than 7 at 5 min, large for gestational age, macrosomia, extreme pre-term birth in pregnant mothers compared with standard BMI mothers. However, the underweight mothers showed increased odds for small for gestational age infant and pre-term birth, whereas obese mothers were at higher risk for post-term birth and stillbirths. The subgroup and meta-regression analyses have shown the impact of BMI cut-offs, geographical region, source of BMI, and sample size on several maternal, fetal/neonatal adverse outcomes.ConclusionThe meta-analysis confirmed the association of elevated pre-pregnancy maternal BMI with higher odds of adverse maternal and fetal/neonatal outcomes.