Mechanisms underlying the role of endoplasmic reticulum stress in the placental injury and fetal growth restriction in an ovine gestation model

Background Exposure to bisphenol A(BPA),an environmental pollutant known for its endocrine-disrupting properties,during gestation has been reported to increase the risk of fetal growth restriction(FGR)in an ovine model of pregnancy.We hypothesized that the FGR results from the BPA-induced insufficiency and barrier dysfunction of the placenta,oxidative stress,inflammatory responses,autophagy and endoplasmic reticulum stress(ERS).However,precise mechanisms underlying the BPA-induced placental dysfunction,and subsequently,FGR,as well as the potential involvement of placental ERS in these complications,remain to be investigated.Methods In vivo experiment,16 twin-pregnant(from d 40 to 130 of gestation)Hu ewes were randomly distributed into two groups(8 ewes each).One group served as a control and received corn oil once a day,whereas the other group received BPA(5 mg/kg/d as a subcutaneous injection).In vitro study,ovine trophoblast cells(OTCs)were exposed to 4 treatments,6 replicates each.The OTCs were treated with 400μmol/L BPA,400μmol/L BPA+0.5μg/m L tunicamycin(Tm;ERS activator),400μmol/L BPA+1μmol/L 4-phenyl butyric acid(4-PBA;ERS antagonist)and DMEM/F12 complete medium(control),for 24 h.Results In vivo experiments,pregnant Hu ewes receiving the BPA from 40 to 130 days of pregnancy experienced a decrease in placental efficiency,progesterone(P4)level and fetal weight,and an increase in placental estrogen(E2)level,together with barrier dysfunctions,OS,inflammatory responses,autophagy and ERS in type A cotyledons.In vitro experiment,the OTCs exposed to BPA for 24 h showed an increase in the E2 level and related protein and gene expressions of autophagy,ERS,pro-apoptosis and inflammatory response,and a decrease in the P4 level and the related protein and gene expressions of antioxidant,anti-apoptosis and barrier function.Moreover,treating the OTCs with Tm aggravated BPA-induced dysfunction of barrier and endocrine(the increased E2 level and decreased P4 level),OS,inflammatory responses,autophagy,and ERS.However,treating the OTCs with 4-PBA reversed the counteracted effects of Tm mentioned above.Conclusions In general,the results reveal that BPA exposure can cause ERS in the ovine placenta and OTCs,and ERS induction might aggravate BPA-induced dysfunction of the placental barrier and endocrine,OS,inflammatory responses,and autophagy.These data offer novel mechanistic insights into whether ERS is involved in BPA-mediated placental dysfunction and fetal development.

Associations of serum D-dimer and glycosylated hemoglobin levels with third-trimester fetal growth restriction in gestational diabetes mellitus

BACKGROUND Gestational diabetes mellitus(GDM)is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism;GDM is diagnosed for the first time during pregnancy and can affect fetal growth and development.AIM To investigate the associations of serum D-dimer(D-D)and glycosylated hemoglobin(HbA1c)levels with third-trimester fetal growth restriction(FGR)in GDM patients.METHODS The clinical data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetrics and Gynecology Hospital of Fudan University from January 2021 to January 2023 were analyzed retrospectively.Among these women,63 whose fetuses had FGR were included in the FGR group,and 101 women whose fetuses had normal body weights were included in the normal body weight group(normal group).Fasting venous blood samples were collected from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c levels for comparative analysis.The diagnostic value of serum D-D and HbA1c levels for FGR was evaluated by receiver operating characteristic analysis,and the influencing factors of third-trimester FGR in GDM patients were analyzed by logistic regression.RESULTS Serum fasting blood glucose,fasting insulin,D-D and HbA1c levels were significantly greater in the FGR group than in the normal group,while the homeostasis model assessment of insulin resistance values were lower(P<0.05).Regarding the diagnosis of FGR based on serum D-D and HbA1c levels,the areas under the curves(AUCs)were 0.826 and 0.848,the cutoff values were 3.04 mg/L and 5.80%,the sensitivities were 81.0%and 79.4%,and the specificities were 88.1%and 87.1%,respectively.The AUC of serum D-D plus HbA1c levels for diagnosing FGR was 0.928,and the sensitivity and specificity were 84.1%and 91.1%,respectively.High D-D and HbA1c levels were risk factors for third-trimester FGR in GDM patients(P<0.05).CONCLUSION D-D and HbA1c levels can indicate the occurrence of FGR in GDM patients in the third trimester of pregnancy to some extent,and their combination can be used as an important index for the early prediction of FGR.

Long-term implications of fetal growth restriction

Fetal growth restriction(FGR),or intrauterine growth restriction(IUGR),is a complication of pregnancy where the fetus does not achieve its genetic growth potential.FGR is characterized by a pathological retardation of intrauterine growth velocity in the curve of intrauterine growth.However,the FGR definition is still debated,and there is a lack of a uniform definition in the literature.True IUGR,compared to constitutional smallness,is a pathological condition in which the placenta fails to deliver an adequate supply of oxygen and nutrients to the developing fetus.Infants with IUGR,compared to appropriately grown gestational age infants,have a significantly higher risk of mortality and neonatal complications with long-term consequences.Several studies have demonstrated how suboptimal fetal growth leads to long-lasting physiological alterations for the developing fetus as well as for the newborn and adult in the future.The long-term effects of fetal growth retardation may be adaptations to poor oxygen and nutrient supply that are effective in the fetal period but deleterious in the long term through structural or functional alterations.Epidemiologic studies showed that FGR could be a contributing factor for adult chronic diseases including cardiovascular disease,metabolic syndrome,diabetes,respiratory diseases and impaired lung function,and chronic kidney disease.In this review we discussed pathophysiologic mechanisms of FGR-related complications and potential preventive measures for FGR.

超声监测结合BUN、UA水平预测PE并发FGR孕产妇不良结局价值

目的:探讨超声胎儿监测结合血尿素氮(BUN)和尿酸(UA)水平预测子痫前期(PE)并发胎儿生长受限(FGR)患者不良结局价值。方法:回顾性收集2020年1月-2023年5月本院就诊的PE患者,其中并发FGR 106例为观察组,未并发FGR患者106例为对照组,比较两组血BUN、UA水平,超声胎儿静脉导管收缩期峰值速度(PSV)、舒张期峰值速度(EDV)、平均时间最大血流速度(Vmax),统计新生儿及孕妇不良结局。结果:观察组血BUN(5.03±1.22mmol/L)、UA(435.54±52.13mmol/L)高于对照组(4.01±1.30 mmol/L、391.60±60.88 mmol/L),PSV(0.85±0.12cm/s)、EDV(0.78±0.11cm/s)、Vmax(0.81±0.13cm/s)低于对照组(0.89±0.11 cm/s、0.96±0.14 cm/s、0.98±0.12 cm/s),新生儿不良结局总发生率(67.9%)高于对照组(15.1%),孕妇不良妊娠结局总发生率(38.7%)高于对照组(20.8%);观察组发生新生儿不良结局患者血BUN、UA高于未发生新生儿不良结局患者,而超声胎儿静脉血流参数均低于未发生新生儿不良结局患者(均P<0.05)。血BUN、UA、PSV、EDV、Vmax及联合预测新生儿不良结局的曲线下面积分别为0.735、0.760、0.643、0.809、0.670和0.706,联合预测的灵敏性达到100.0%。结论:PE并发FGR患者BUN、UA水平异常升高,超声胎儿静脉血流参数异常降低,上述超声及血指标预测新生儿不良结局有一定临床指导价值。

基于彩色多普勒超声分析胎儿脐血流对FGR的诊断价值

目的:探讨彩色多普勒超声胎儿脐血流参数对FGR的诊断价值。方法:回顾性选取2019年12月~2021年12月收治的100例FGR孕妇(研究组)及100例正常孕妇(对照组),均接受超声检测。分析胎儿超声脐血流参数与FGR的关系,Logistic回归分析FGR发生的影响因素。ROC曲线分析胎儿脐血流参数对FGR的诊断价值。结果:Logistic分析显示年龄、羊水过少、低蛋白血症、RI,PI,S/D均是FGR发病的影响因素。ROC分析显示S/D、RI、PI对FGR诊断价值高。结论:FGR胎儿彩色多普勒RI,PI,S/D异常升高,具有良好诊断价值。

Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction

From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg taurine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neo- natal rats with intrauterine growth restriction undergoing taurine supplement were obtained for fur- ther experiments. The terminal deoxyribonucleotidyl transferase （TdT）-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. Immu- nohistochemical staining revealed that taurine supplement increased glial cell line-derived neuro- trophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.

Effect of Bushen Yiqi Huoxue Recipe on Placental Vasculature in Pregnant Rats with Fetal Growth Restriction Induced by Passive Smoking

Interactions of vascular endothelial growth factor （VEGF） with receptors VEGFR1/Fltl and VEGFR2/Flk1, and those of angiopoietins （Ang-1, Ang-2） with receptor Tie2 play important roles in placental angiogenesis. This study investigated vascular morphology and expression of these angiogenic factors in rat placenta on the day 15, 18, 21 of gestation （D 15, D 18 and D21）. The rats were randomly assigned into 3 groups： normal group, model group [fetal growth restriction （FGR） model], and Bushen Tqi Huoxue （BYHR） recipe treatment group （BYHR group, the pregnant rats with FGR were treated with BYHR recipe）. Morphological analysis indicated that during initial villous formation, fetal nucle- ated erythrocytes （FNEs） appeared in maternal blood sinus （MBS）. Subsequently, FNEs were sur- rounded by endothelial cells to form fetal capillary （FC） and then by trophoblast cells to form villi. As pregnancy proceeded, FC density increased progressively with increasing endothelial identification staining （EIS） in normal and BYHR groups. Whereas, villous formation was suppressed, normal in- crease in FC density was impaired and EIS was weakened in model group. Quantitative PCR analysis showed that VEGF and Flkl mRNA increased over gestation in all groups, indicating that VEGF might play a pivotal role in FC growth during late gestation. VEGF mRNA was increased on D15, while de- creased on D21 in model group as compared with normal group and BYHR group. Immunohistochemi- cally, Ang-2 protein was highly expressed in FNEs, gradually disappeared as villi matured, and decreased over gestation in all groups, indicating that Ang-2 might play a pivotal role in villous formation, which was further supported by decreased Ang-2 mRNA and protein expression in model group on D 15. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio increased from D15 to D18 in all groups as placenta matured. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio were decreased on D18 in model group as compared with normal and BYHR groups, indicating delayed maturity of FGR placenta. Alterations in angiogenic factors may result in altered placental vasculature and cause placental insufficiency. BYHR recipe could balance the angiogenic factors to promote the formation and maturation of FGR placental vasculature.

Expression of soluble vascular endothelial growth factor receptor-1 and placental growth factor in fetal growth restriction cases and intervention effect of tetramethylpyrazine

Objective:To investigate the expression of soluble vascular endothelial growth factor receptor-1(sFlt-1) and placental growth factor(PLGF) in the fetal growth restriction(FGR) cases and the intervention mechanism of tetramelhylpyrazine.Methods:A total of 60 fetal growth restriction cases that admitted lo our hospital were randomly divided into ligustrazine intervention group(group A) and nutritional support group(group B).A total of 50 healthy pregnant women were also enrolled as control group(group C).Expression level of maternal serum sFlt1,FLGF and fetal growth parameters including HC,AC,FL,BPD,EFW as well as placenta PLGF,sFlt-1 mRNA expression were recorded and compared among the three groups.A total of 15 SD rats were selected and were divided into lliree groups.TMP group,alcohol and tobacco group and blank control group.Three groups of rats were dissected on the twentieth day of gestation.Result:Expression level of sFlt-1 and PLGF in group A was not significantly different from that of group C(P>0.05):but significant difference in SFlt1 and PLGF expression level was observed between group C and group B(P<0.05).Before treatment.HC,AC,FL,BPD and EFW of group A and group B were significant lower than those of group C.hut after treatment,those parameters in group A were significantly improved(P<0.05).In the animal experiment there was no significant difference in sFlt-1 between treatment group and FGR group without treatment or control group(P>0.05).There was significant difference in PLGF between FGR group with treatment and FGR group without treatment or control group(P<0.01).Conclusions:PLGF level is decreased and sFlt-1 increased in patients suffered from fetal growth restriction,and FGR rats show increased sFlt-1 and decreased PLGF.thus they can be indicator of the fetal growth restriction.Ligustrazinc can effectively improve sFlt-1,PLGF expression level in fetal growth restriction cases,which can be used as treatment for FGR.

Concentrations of Polybrominated Diphenyl Ethers in Maternal Blood,Placental Size,and Risk for Fetal Growth Restriction:A Nested Case-control Study

Objective To explore the effects of prenatal exposure to polybrominated diphenyl ethers(PBDEs)on placental size and birth outcomes.Methods Based on the perspective Wenzhou Birth Cohort,this nested case-control study included 101 fetal growth restriction(FGR)and 101 healthy newborns.Maternal serum samples were collected during the third trimester and measured for PBDEs by gas chromatography tandem mass spectrometry.The basic information of mother-newborn pairs was collected from questionnaires,whereas the placental size and birth outcomes of newborns were obtained from hospital records.Results A total of 19 brominated diphenyle ether(BDE)congeners were detected in maternal serum samples.Higher concentrations of BDE-207,-208,-209,and∑19PBDEs were detected in FGR cases than in controls.Increased BDE-207,-208,-209,and∑19PBDEs levels in maternal serum were related to decreased placental length,breadth,surface area,birth weight,birth length,gestational age,and Quetelet index of newborns.After adjusting for confounders,BDE-207 and∑19PBDE concentrations in maternal serum were significantly associated with an increased risk of FGR.Conclusion A negative association was found between PBDE levels in maternal serum and placental size and birth outcomes.Prenatal PBDE exposure may be associated with elevated risk of the incidence of FGR birth.

Effect of behavior training on learning and memory of young rats with fetal growth restriction

Objective: To investigate the effect of behavior training on the learning and memory of young rats with fetal growth restriction (FGR). Methods: The model of FGR was established by passive smoking method to pregnant rats. The new-born rats were divided into FGR group and normal group, and then randomly subdivided into trained and untrained group respectively. Morris water maze behavior training was performed on postnatal months 2 and 4, then learning and memory abilities of young rats were measured by dark-avoidance testing and step-down testing. Results: In the dark-avoidance and step-down testing, the young rats’ performance of FGR group was worse than that of control group, and the trained group was better than the untrained group significantly. Conclusion: FGR young rats have descended learning and memory abilities. Behavior training could improve the young rats’ learning and memory abilities, especially for the FGR young rats.

Impairments of spatial learning and memory in rat offspring with fetal growth restriction

Objective： Throughout the world, fetal growth restriction（FGR） is one of the most severe complications occurring during pregnancy. It is subsequently associated with neurologic abnormalities in chldren. Our aim was to investigate the spatial learning and memory ability of rat offspring born With FGR. Methods：A rat model of FGR was constructed using the method of passive smoking. Spatial learning and memory were studied in rat offspring born with FGR by assessing the animals＇ performance using the Morris water maze task. Results： At 1- and 2- months of age, both female and male offspring rats showed impairment of performance, while at 4 months of age, only female rats showed impaired performance. The FGR offspring spent a longer time swimming and used inefficient strategies（P〈 0.05, respectively）. However, there were no significant maze performance FGR effects in the 4 month old male rats. In all groups of FGR offspring, irrespective of age or sex, the time spent in the platform quadrant by the rat was significantly less than that in the control group（P〈 0.05）. Conclusion： The Morris water maze performance decreased in rat offspring born with FGR. It is suggested that FGR can cause impairments of spatial learning and memory in young animals.

补肾益气活血方对FGR大鼠小肠上LAT1表达的影响

目的观察补肾益气活血方对宫内生长受限(fetal growth restriction,FGR)大鼠小肠上氨基酸转运蛋白LAT1表达的影响,探讨该方治疗胎儿宫内生长受限的可能机制。方法应用被动吸烟法构建Wistar大鼠FGR模型,将35只孕鼠随机分为空白组、模型组、中药组、西药组及中西药结合组,其中5只孕鼠未获得胎鼠,最终30只孕鼠入组。采用Realtime RT-PCR法、Western Blot法检测胎鼠及孕鼠小肠上氨基酸转运蛋白LAT1(SLC7A5)及其重链4F2hc(SLC3A2)的mRNA及蛋白表达,并比较其表达差异。结果FGR模型组孕鼠小肠上氨基酸转运蛋白LAT1及其对应mRNA SLC7A5表达上调,经补肾益气活血方和(或)精氨酸治疗后出现不同程度的表达下调,且各治疗组胎鼠体重均高于FGR模型组。结论孕鼠小肠上LAT1蛋白及mRNA表达下调可能与补肾益气活血方治疗宫内生长受限的作用机制有关。

Expression of Lung Surfactant Proteins SP-B and SP-C and Their Modulating Factors in Fetal Lung of FGR Rats

This study investigated the expression of lung surfactant proteins SP-B and SP-C, and their modulating factors TTF-1 and PLAGL2 in the fetal lung of rats with fetal growth restriction（FGR）. The rat FGR model was established by prenatal hypoxia in the first stage of pregnancy, 180 rats for experiment served as hypoxia group, and 197 healthy rats served as normal control group. The FGR incidence in hypoxia was compared with that in normal control group. The histological changes in the fetal lung were observed under the light microscope and electronic microscope in two groups. The SP-B, SP-C, TTF-1 and PLAGL2 proteins were determined in the fetal lung of two groups immunohistochemically. The expression levels of SP-B, SP-C, TTF-1 and PLAGL2 protein and m RNA in the fetal lung of two groups were detected by using Western blotting and RT-PCR respectively. The FGR rat model was successfully established by using hypoxia. Pathologically the fetal lung developed slowly, and the expression levels of SP-B, SP-C, TTF-1 and PLAGL2 protein and mR NA in the fetal lung were significantly reduced in hypoxia group as compared with those in normal control group. It was suggested that maternal hypoxia in the first stage of pregnancy could induce FGR, and reduce the expression of SP-B and SP-C, resulting in the disorder of fetal lung development and maturation.

Different Fetal and Neonatal Growth between Early- and Late-Onset Preeclampsia

Preeclampsia is a heterogeneous disease, and there are major differences in severity, fetal growth and poor placentation between early- and late-onset preeclampsia. Here, we examined the effect of onset period on fetal and neonatal growth in preeclampsia with a cross-sectional study including 102 pregnant women with preeclampsia visited Okayama University Hospital from 2009 to 2013. The subjects were retrospectively compared in terms of body mass index (BMI), weight gain during pregnancy, complications, weeks of delivery, neonatal body weight and BMI at birth, fetal growth restriction (FGR), small for gestational age (SGA), pathological findings in the placenta, and infant’s weight at 1 month after birth. Neonatal body weight and BMI at birth were significantly lower and the extent of FGR and the frequency of SGA were higher in early-onset group compared with late-onset group. Mean daily weight gain during the neonatal period was significantly lower in the early-onset group compared with the late-onset group, however the weight gain rate during the neonatal period in the early-onset group was higher than that in late-onset group. In conclusions, there are significant differences in fetal and neonatal growth between early- and late-onset preeclampsia and the catch up for growth might start during neonatal period.

胎盘血流状态及胎儿大脑中动脉血流和脑胎盘率预测晚发型FGR的超声研究

目的研究胎盘血流状态及胎儿大脑中动脉血流和脑胎盘率预测晚发型胎儿生长受限。方法选择在本院分娩胎儿受限的产妇120例为病例组,同时选择同期产检、分娩正常胎儿的60例产妇为对照组。三维多普勒超声检测胎盘血流状态、脑胎盘率、大脑中动脉血流参数等,单因素分析临床基线资料,Logistic回归分析确定胎儿生长发生的影响因素,通过受试者工作特征曲线分析各指标及回归分析诊断效能。结果病例组孕妇血流指数(blood flow index,FI)、血管化指数(vascularization index,VI)和血管化-血流指数(vascularization-blood flow index,VFI)等胎盘血流状态参数明显低于对照组。病例组孕妇搏动指数(pulsatility index,PI)、阻力指数(resistance index,RI)和脑胎盘率(cerebroplacental ratio,CPR)明显低于对照组,病例组孕妇EDV明显高于对照组。CPR与FI、VI、VFI、PI和RI成正相关(r=0.185,0.594,0.854,0.696,0.701,P<0.05);CPR与EDV成负相关(r=-0.452,P<0.05)。Logistic回归分析结果表明,FI、VI、VFI、PI、RI、EDV和CPR是胎儿生长受限的影响因素。结论脑胎盘率、胎盘血流状态及大脑中动脉血流参数在胎儿生长受限孕妇中异常表达,且CPR、FI、VI、VFI、PI、RI及EDV等参数单独和Logistic回归分析可应用于胎儿生长受限的预测和诊断。

FGR母体胎盘血管灌注不良的影响因素分析

目的探讨与分析胎儿生长受限(fetal growth restriction,FGR)母体胎盘血管灌注不良的影响因素。方法选择2022年1月—2023年1月在北大医院宁夏妇儿医院、宁夏回族自治区妇幼保健院及银川市妇幼保健院住院分娩并诊断为胎儿生长受限的87例产妇作为研究对象,所有产妇都给予超声检查,记录脐动脉血流动力学参数。同时所有产妇都给予胎盘病理检查,判定母体胎盘血管灌注不良发生情况,调查产妇的一般资料并进行相关性分析。结果在87例产妇中,判断为母体胎盘血管灌注不良27例,占31.0%(灌注不良组),其中绒毛梗死14例、远端绒毛发育不良6例、绒毛成熟加速4例、蜕膜动脉病3例。灌注不良组产妇的子痫前期史、胎盘早剥史等占比高于非灌注不良组,差异有统计学意义(P<0.05)。两组胎儿脐动脉收缩期峰值流速对比,差异无统计学意义(P>0.05);灌注不良组的舒张末期血流速度低于非灌注不良组,搏动指数、阻力指数高于非灌注不良组,差异有统计学意义(P<0.05)。在87例产妇中,Spearman分析显示母体胎盘血管灌注不良与脐动脉舒张末期血流速度、搏动指数、阻力指数等存在相关性,差异有统计学意义(P<0.05)。二元Logistics回归分析显示,脐动脉舒张末期血流速度、搏动指数、阻力指数为导致母体胎盘血管灌注不良发生的重要因素,差异有统计学意义(P<0.05)。结论胎儿生长受限产妇的母体胎盘血管灌注不良发生率比较高,脐动脉舒张末期血流速度、搏动指数、阻力指数为导致母体胎盘血管灌注不良发生的重要因素,胎盘母体血管灌注情况能够为治疗改善胎儿生长受限预后提供依据。

低分子肝素治疗胎盘脐带因素FGR的临床研究

目的 探讨低分子肝素治疗胎盘脐带因素胎儿宫内生长受限(FGR)的临床效果。方法 选取2021年1月至2023年4月我院收治的胎盘脐带因素FGR孕妇92例,根据入院顺序将其分为两组,对照组予以补钙补铁及加强营养治疗,观察组予以低分子肝素联合阿司匹林、补钙补铁及加强营养治疗。比较两组的治疗效果、胎儿生长发育情况、血流参数情况、孕妇瘦素(Lep)、血清胰岛素样生长因子-1(IGF-1)、新生儿不良结局。结果 观察组治疗效果高于对照组(P <0.05);观察组胎儿头围、双顶径、宫高大于对照组(P <0.05);观察组RI、PI、S/D大于对照组(P <0.05);观察组孕妇Lep、IGF-1水平高于对照组(P <0.05);观察组新生儿不良结局少于对照组(P <0.05)。结论 低分子肝素治疗胎盘脐带因素FGR临床效果较好,可对母婴结局进行改善,应用价值较高。

miR-34c-5p靶向poFUT1对胎盘血管形成的影响

目的:探讨miR-34c-5p与poFUT1的靶向关系及对胎盘血管形成的影响。方法:利用ENCORI数据库预测miR-34c-5p与poFUT1的结合位点,采用双荧光素酶报告实验验证。随机选取2023年4至10月在郑州大学第三附属医院住院的胎儿生长受限(FGR)孕妇20例(FGR组),选择同期正常孕妇20例为对照。采用实时荧光定量PCR法检测两组胎盘组织中miR-34c-5p和poFUT1 mRNA的表达。取脐静脉内皮细胞,分组转染miR-34c-5p模拟物及其对照(NC)、miR-34c-5p抑制物及其NC、si-poFUT1 NC、si-poFUT1、si-poFUT1+miR-34c-5p抑制物,采用CCK-8法、Transwell实验以及成管实验检测细胞转染24、48、72、96 h后的增殖能力,转染48 h后的侵袭能力和成管能力。结果:FGR组和对照组胎盘组织中miR-34c-5p表达水平分别为(1.57±0.39)、(1.09±0.18),poFUT1 mRNA表达水平分别为(0.51±0.17)、(1.06±0.13),FGR组胎盘组织中miR-34c-5p表达水平高于对照组,poFUT1 mRNA表达水平低于对照组(P<0.05)。与miR-34c-5p模拟物NC组比较,模拟物组侵袭细胞数和管腔节点数减少,细胞增殖活性降低(P<0.05)。与miR-34c-5p抑制物NC组比较,抑制物组侵袭细胞数和管腔节点数增加,细胞增殖活性升高(P<0.05)。与si-poFUT1 NC组相比,si-poFUT1组侵袭细胞数和管腔节点数减少,细胞增殖活性降低(P<0.05),而si-poFUT1+miR-34c-5p抑制物组上述变化较si-poFUT1组部分逆转(P<0.05)。结论:miR-34c-5p可能通过调控poFUT1影响血管内皮细胞功能,从而影响胎盘的血管形成,参与FGR的发生。

胎儿生长受限患者胎盘组织中VEGFA、HIF-1α表达及临床意义

目的:探究胎儿生长受限(FGR)患者胎盘组织中血管内皮生长因子A(VEGFA)、缺氧诱导因子(HIF)-1α表达及临床意义。方法:选择2020年5月-2022年9月在本院确诊FGR并住院分娩的孕妇116例(FGR组)、分娩正常孕妇(新生儿正常)116例为对照组临床资料。qRT-PCR检测胎盘组织中VEGFA、HIF-1α的mRNA表达情况,免疫组化法检测VEGFA、HIF-1α的蛋白表达情况。Pearson相关性分析VEGFA与HIF-1α的相关性以及与FGR患者临床资料相关性;多因素logistic回归分析影响FGR发生的因素。结果:FGR组VEGFA蛋白阳性表达率(25.9%)低于对照组(64.7%),HIF-1α蛋白阳性表达率(67.2%)高于对照组(24.1%);FGR组胎盘组织中VEGFA mRNA表达水平(0.75±0.20)低于对照组(1.00±0.23),HIF-1α mRNA表达水平(1.26±0.25)高于对照组(1.01±0.19)(均P<0.05)。FGR患者胎盘组织中VEGFA mRNA与HIF-1α mRNA呈负相关(P<0.05)。FGR患者新生儿出生1 min Apgar评分、胎盘重量、胎盘体积、新生儿体重与VEGFA表达水平呈正相关,与HIF-1α表达水平呈负相关;HIF-1α升高为影响FGR发生的危险因素,VEGFA升高为保护因素(均P<0.05)。结论:FGR患者胎盘组织中VEGFA低表达、HIF-1α高表达,二者影响FGR的发生及新生儿出生质量。

三维能量多普勒超声参数联合胎盘生长因子对早发型胎儿生长受限的预测价值

目的探讨三维能量多普勒超声参数联合胎盘生长因子(PLGF)对早发型胎儿生长受限(FGR)的预测价值。方法选取早发型FGR孕妇80例为FGR组,另选取同期产检健康孕妇50例为对照组。在孕11~13周+6对所有研究对象进行三维能量多普勒超声检查,收集胎盘容积(PV)、血管化指数(VI)、血流指数(FI)、血管化-血流指数(VFI)等指标。在孕14~16周+6检测所有研究对象血清PLGF水平。结果FGR组的PV、VI、FI、VFI以及血清PLGF水平均低于对照组,差异有统计学意义(P<0.05)。多元Logistic回归方程分析显示,PV、VI、FI、VFI以及血清PLGF水平过低是早发型FGR的危险因素(P<0.05)。受试者工作特征(ROC)曲线分析显示,PV、VI、VFI以及血清PLGF均对早发型FGR有一定的预测价值,曲线下面积分别为0.723(95%CI:0.629~0.817)、0.776(95%CI:0.693~0.860)、0746(95%CI:0.653~0.839)、0.799(95%CI:0.713~0.884),FI对早发型FGR的预测价值一般,曲线下面积为0.625(95%CI:0.524~0.725)。经分析显示,PLGF联合VI以及PLGF联合VFI对早发型FGR的预测价值较好,PLGF联合VI的敏感度、特异度和约登指数分别为86.25%、76.00%、0.623,PLGF联合VFI的敏感度、特异度和约登指数分别为81.25%、80.00%、0.613。结论三维能量多普勒超声参数联合PLGF对早发型FGR有一定的预测价值,可用于临床筛查早发型FGR高风险人群。