The choice of amniotic fluid in metabolomics for the monitoring of fetus health

Amniotic fluid (AF) is a biological fluid in which metabolite transport is regulated by the placenta, the permeable skin, fetal lung egress and gastric fluid. During pregnancy, the composition of AF changes from similar to the interstitial fluid of the mother, to a more complex system, influenced by the fetus’s urine. Since AF reflects the mother’s and the fetus’s health status at the same time, it may be an important diagnostic tool for a wider spectrum of clinical conditions. Indeed, the metabolic characterization of AF in relation to pathological occurrences may lead to the discovery of new biomarkers for a better clinical practice. For this reason, metabolomics may be the most suitable strategy for this task. In this review, research works on metabolomic AF analysis are discussed according to the morbidity of interest, being preterm birth/labor, gestational age and diabetes and fetal malformations, along with a number of other important studies.     

对比不同超声估重公式预测巨大胎儿体质量

目的 观察不同超声估重（SFEW）公式预测巨大胎儿的准确率，分析其影响因素。方法 回顾629例巨大儿，根据体质量分为A组和B组；将产前超声所测双顶径（BPD）、头围（HC）、腹围（AC）及股骨长（FL）代入不同公式，比较SFEW预测值与出生后实测值的差异。结果 不同估算公式SFEW测值均明显低于实测值（P均<0.001），其中Hadlock公式预测值与实测值的差异最小；产前超声生物学测值与出生后实测体质量及身长低度相关（r_s<0.50）。B组身长、体质量指数（BMI）及各超声生物学测值均明显大于A组（P均<0.05）；不同公式计算B组误差均明显大于A组（P均<0.05）。结论 SFEW有效可行，但易低估胎儿体质量，各公式参数不能充分体现巨大胎儿躯干外脂肪分布差异对体质量的影响可能是原因之一。     

In vitro fabrication of autologous living tissue‐engineered vascular grafts based on prenatally harvested ovine amniotic fluid‐derived stem cells

Amniotic fluid cells (AFCs) have been proposed as a valuable source for tissue engineering and regenerative medicine. However, before clinical implementation, rigorous evaluation of this cell source in clinically relevant animal models accepted by regulatory authorities is indispensable. Today, the ovine model represents one of the most accepted preclinical animal models, in particular for cardiovascular applications. Here, we investigate the isolation and use of autologous ovine AFCs as cell source for cardiovascular tissue engineering applications. Fetal fluids were aspirated in vivo from pregnant ewes (n = 9) and from explanted uteri post mortem at different gestational ages (n = 91). Amniotic non‐allantoic fluid nature was evaluated biochemically and in vivo samples were compared with post mortem reference samples. Isolated cells revealed an immunohistochemical phenotype similar to ovine bone marrow‐derived mesenchymal stem cells (MSCs) and showed expression of stem cell factors described for embryonic stem cells, such as NANOG and STAT‐3. Isolated ovine amniotic fluid‐derived MSCs were screened for numeric chromosomal aberrations and successfully differentiated into several mesodermal phenotypes. Myofibroblastic ovine AFC lineages were then successfully used for the in vitro fabrication of small‐ and large‐diameter tissue‐engineered vascular grafts (n = 10) and cardiovascular patches (n = 34), laying the foundation for the use of this relevant pre‐clinical in vivo assessment model for future amniotic fluid cell‐based therapeutic applications. Copyright © 2013 John Wiley & Sons, Ltd.     

<Emphasis Type="Italic">For Debate: </Emphasis>Fetal and early postnatal growth restriction lead to diabetes,the metabolic syndrome and renal failure*

We review the progress in testing the thrifty phenotype hypothesis. Many human epidemiological studies both by ourselves and others have confirmed and extended the original observations on which the hypothesis was based. We are not aware of any contradictory findings and we emphasise the strength of the association between birth weight and the subsequent development of the metabolic syndrome. We have worked extensively experimentally to test the hypothesis in a rat model in which pregnant and/or lactating dams are fed a diet moderately restricted in proteins. The range of programming effects that we have discovered in this example of fetal and early postnatal growth restriction is listed and includes changes in hormone receptors, signalling molecules and regulatory enzymes. We have shown the model to develop diabetes, the metabolic syndrome and signs of premature renal failure. We summarise these and other similarities between the phenotype of this model and human Type 2 diabetes and the metabolic syndrome. The number of insults during early development which can lead to a similar outcome is discussed and the suggestion is made that the early life response to stress is limited in its flexibility with outcomes including ageing and decreased longevity. Our preliminary results indicate that some MODY genes could suggest pathways whereby the changes occur and that epigenetic changes during development are involved. We conclude that the way is now clear to discover early human markers of programming by early life growth restriction and to use these to devise strategies for the prevention of Type 2 diabetes.*Based upon the Dorothy Hodgkin Lecture delivered by CNH at the Birmingham Meeting of Diabetes UK, March 2002     

Morphology,molecular phenotypes and distribution of neurons in developing human corpus callosum

The aim of this study was to investigate the morphology, molecular phenotypes, distribution and developmental history of interstitial neurons in the human corpus callosum, here defined as intracallosal neurons. We analysed 26 fetuses, three newborns, five infants and children, and eight adults [age range – 15 weeks postconception (PCW) to 59 years] by means of acetylcholinesterase (AChE) histochemistry and immunohistochemistry for neuron markers (MAP2, NeuN, NPY, calretinin and calbindin). We found a heterogeneous neuron population, positioned within the callosal trunk itself (aside from neurons present in the transient midline structures such as callosal sling, septa or subcallosal zone), which was most numerous during the second half of gestation and early postnatal years. We named these cells intracallosal neurons. At 15 PCW, the intracallosal neuron population consisted of poorly differentiated, small fusiform or bipolar, migratory‐like MAP2‐ or calretinin‐positive neurons which could be observed until mid‐gestation. Later the population comprised morphologically diverse, predominantly well‐differentiated MAP2‐, NPY‐, calbindin‐ and AChE‐positive neurons. The morphological differentiation of intracallosal neurons culminated in the newborns and remained pronounced in infants and children. In the adult brain, the intracallosal neurons were found only sporadically, with small somata and poorly stained dendrites. Thus, intracallosal neurons form part of a transitory neuron population with a developmental peak contemporaneous to the critical period of callosal formation. Therefore, they may be involved in processes such as axon guiding or elongation, withdrawal of exuberant axons, fasciculation, or functional tuning, which occur at that time.     

The tyrosine kinase inhibitor dasatinib dysregulates bone remodeling through inhibition of osteoclasts in vivo

Dasatinib is a potent tyrosine kinase inhibitor that is used to treat chronic myeloid leukemia in patients resistant or intolerant to imatinib mesylate. While designed to inhibit Abl and Src kinases, dasatinib shows multitarget effects, including inhibition of the macrophage colony‐stimulating factor (M‐CSF) receptor c‐fms. We have shown previously that dasatinib abrogates osteoclast formation and activity in vitro owing, in part, to its specificity for c‐fms. In this study we examined whether dasatinib could significantly alter bone volume in a model of physiologic bone turnover. Sprague‐Dawley rats were administered dasatinib (5 mg/kg/day) or vehicle by gavage or zoledronic acid (ZOL; 100 µg/kg/6 weeks) subcutaneously. Following 4, 8, and 12 weeks of treatment, serum biochemical, bone morphometric, and histologic analyses were performed. Whole‐body bone mineral density and tibial cortical thickness where unchanged in the dasatinib‐ or ZOL‐treated animals relative to controls. However, micro–computed tomographic (µCT) analysis of cancellous bone at the proximal tibias showed that trabecular volume (BV/TV) and thickness (Tb.Th) were increased in dasatinib‐treated animals at levels comparable with those of the ZOL‐treated group. These changes were associated with a decrease in osteoclast numbers (N.Oc/B.Pm) and surface (Oc.S/BS) and decreased serum levels of the osteoclast marker c‐terminal collagen crosslinks (CTX‐1). Mineral apposition rate (MAR), bone‐formation rate (BFR), and levels of the serum osteoblast markers osteocalcin and N‐terminal propeptide of type I procollagen (P1NP) were not altered significantly in the dasatinib‐treated animals relative to controls. These studies show that dasatinib increases trabecular bone volume at least in part by inhibiting osteoclast activity, suggesting that dasatinib therapy may result in dysregulated bone remodeling. © 2010 American Society for Bone and Mineral Research     

136例晚期羊水过少胎心监护无应激试验波形与分娩结局的关系

目的：探讨羊水过少孕妇胎心监护无应激试验（NST）异常波形与分娩结局的关系。方法：回顾分析在本院足月单胎头位分娩的3420名孕产妇中,羊水过少136例NST监护的波形,并随机抽查同期住院分娩的140例羊水正常的孕妇作为对照,所有孕妇均在产前1～2d进行NST监护20～40 min,对比分析NST监护波形与羊水量及新生儿结局,所有病例均无其他病理因素。结果：羊水过少组中NST基线变异消失和NST自然减速等异常,剖宫产率增加,新生儿窒息率增加及病死率增高。结论：对羊水过少孕妇NST监护波形分析,可及时发现胎儿窘迫的危险信号,基线变异消失或NST自然减速与新生儿窒息的发生相关。