Preeclampsia (PE) is a serious complication of pregnancy, causing irreversible damage to multiple systems and organs of both mother and baby, and can even be life-threatening. Early diagnosis and intervention are key to improving maternal and fetal outcomes. Traditional diagnostic methods primarily rely on clinical symptoms and relatively single laboratory indicators, suffering from issues such as low sensitivity and insufficient specificity. Treatment is limited to symptomatic drug therapy for hypertension, and apart from terminating the pregnancy, there is a lack of effective treatment options. In recent years, Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) has shown great potential in disease biomarker screening due to its advantages of high sensitivity, high throughput, and rapid analysis. This study utilized MALDI-TOF MS technology based on novel inorganic nanosilica material, combined with high-throughput multi-omics(proteomics, peptidomics and metabolomics) analysis, to perform machine learning modeling and optimization analysis on 159 samples from the First People’s Hospital of Yunnan Province. Testing on the validation cohort showed an AUC value as high as 0.93 for preeclampsia detection, with the model’s efficiency and accuracy surpassing traditional diagnostic methods. Furthermore, the machine learning model analysis identified 20 potential biomarkers associated with preeclampsia. By constructing a diagnostic model for preeclampsia onset, this study can provide a basis for exploring the pathological mechanisms of preeclampsia. Simultaneously, it offers a novel technical approach for the screening and prediction of preeclampsia, holding significant clinical application value.
Purpose:To detect the levels of cadmium (Cd) and zinc (Zn) in maternal blood, umbilical blood, and placenta of preeclampsia (PE) patients, elucidating their relationship with FOXO3a transcription factors and oxidative stress. Patients and Methods:A total of 100 pregnant women admitted for childbirth at the obstetrics department of the First People's Hospital of Yunnan Province from September 2023 to September 2024 were included (normal group: 40 cases, PE group: 60 cases). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure Cd and Zn levels in maternal blood, umbilical cord blood, and placental tissues. Enzyme-linked immunosorbent assay (ELISA) was applied to detect Forkhead box O3a (FOXO3a) levels. Statistical analysis was performed using SPSS 27.0 software and RStudio to compare differences and correlations among groups. Perform post hoc statistical efficacy analysis on sample size using G*Power software. Results:Compared with the normal group, placental Cd levels were significantly higher in the PE group (P<0.05) and the maternal blood and placental Zn levels were significantly lower in the PE group (P<0.05). In the PE group, the levels of Zn and Cd in maternal blood and placenta were positively correlated (r=0.50, P<0.001; r=0.567, P<0.001). Placental FOXO3a levels were significantly elevated in the PE group (P<0.001), while maternal and umbilical cord blood FOXO3a levels were reduced (P<0.001). The levels of FOXO3a in the placenta were negatively correlated with the levels of Zn (r=-0.277, P<0.05), and the levels of FOXO3a in umbilical cord blood were negatively correlated with the levels of Cd (r=-0.326, P<0.05). Conclusion:The exposure and accumulation of Cd in the maternal-fetal system can affect the transport and metabolism of Zn in placenta, leading to increased expression of FOXO3a under oxidative stress, causing the occurrence and development of PE.
Purpose: As two of the most severe and common medical disorders during pregnancy, gestational diabetes mellitus (GDM) and hypertensive disorder complicating pregnancy (HDCP) cause adverse effects on placental barrier function and thus may lead to a high risk of intrauterine exposure to toxic metals from mother to fetus. This study investigates the impact of the placental barrier on the transfer of cadmium (Cd) from mother to fetus and the relationship between pregnancy complications. Methods: A total of 107 pairs of samples were collected in Kunming, China; 29 were from healthy pregnant women, and 78 were from patients with pregnancy complications. Cd was measured in each mother's placenta and maternal and umbilical cord blood. The expressions of MT and Cd-MT complex in blood and placental tissue samples were determined by enzyme-linked immunosorbent assay (ELISA). Results: The cesarean section rate in the whole pathological group (60.7%) was higher than that in the normal group (20.7%), and the ratio of the effective barrier (ratio of maternal blood to umbilical cord blood>1) in the pathological group (74%) was lower than that in the normal group (79%). In addition, the proportion of practical placental barriers in women aged 20-25 years was 83.3%, 76.3% in women aged 26-30 years, 74.3% in women aged 31-35 years, 70% in women aged 36-40 years, and 71% in women aged 40-45 years. The Cd content in the placenta of the three pathological groups was significantly higher than that in maternal and umbilical cord blood (P<0.05), and the distribution of Cd was the same as that in the normal group. However, there was no significant difference between maternal and umbilical cord blood Cd concentrations in the pathological group. The Cd concentration in the normal group's maternal blood was significantly higher than that in cord blood (P<0.05). In addition, the expression levels of both metallothionein (MT) and Cd-MT complex in placenta is much higher than in maternal and umbilical blood, and which in normal group are significantly higher than those in pathological group. Conclusion: Both mothers and fetuses are at increased health risk for pregnancy disorders when maternal age, BMI, or body weight increases. Increased maternal age increases the likelihood of Cd transfer from the mother to the fetus. Pregnancy complications may induce lower expression of MT, thus reducing the Cd-MT complex in the placenta, weakening the placental barrier, and increasing the risk of Cd transfer and exposure to the fetus.
Background Hypertensive disorders complicating pregnancy (HDCP) and gestational diabetes mellitus (GDM) can affect the placental barrier function to varying degrees. However, current studies show that the transfer and distribution characteristics of trace elements in the maternal-fetal system are still unclear. This study investigated the effect of the placental barrier on the transfer of trace elements from mother to fetus and its relationship with HDCP and GDM. Methods A case-control method was used in this study. 140 pairs of samples were collected; 60 were from healthy pregnant women, and 80 were from patients with pregnancy complications. The contents of trace elements in paired samples were determined by inductively coupled plasma–mass spectrometry (ICP-MS). SPSS software was used to analyze the differences in trace element levels in matched samples of each group. The correlations were analyzed based on Pearson’s correlation factor (r). Results The distribution characteristics of Fe content in the pathological group (HDCP group and GDM group) were the same as those in the normal group (umbilical cord blood > maternal blood > placenta), but there was no significant difference in the iron content in maternal blood and cord blood of pathological group. The distribution characteristics of Mn content in the pathological group (placenta > umbilical cord blood > maternal blood) were changed compared with those in the normal group (placenta > maternal blood > umbilical cord blood). In addition, the placental Cr content and cord blood Cr and Ni content of the pathological group were higher than those of the normal group. HDCP placental Cr and GDM placental Fe levels were significantly correlated with the Apgar score. Conclusions The transfer of Fe and Mn and the placental barrier function of Cr and Ni in the maternal-fetal system of HDCP and GDM are significantly altered, which directly or indirectly increases the maternal and fetal health risk.
目的 探讨云南省昆明市妊娠期高血压疾病(HDCP)和妊娠期糖尿病(GDM)母胎体系中铜(Cu)和铬(Cr)的分布及转运特征.方法 选取2015年1月—2019年12月在云南省第一人民医院产科住院分娩的产妇72例为研究对象,采用电感耦合等离子质谱法(ICP-MS)测定其配对样本(母血、胎盘及脐血)中Cu和Cr的含量,采用SPSS软件进行数据分析.结果 正常组母胎体系中Cu分布特征胎盘[(43.96±11.13)ng/kg]>母血[(31.22±9.10)ng/kg]>脐血[(8.28±4.21)ng/kg],差异均具有统计学意义(t=-4.772、12.318及16.145,均P<0.05),而GDM组与HDCP合并GDM组Cu分布不同:母血>胎盘>脐血.GDM组胎盘Cu[(31.96±12.54)μg/kg]显著低于正常组胎盘[(43.96±11.13)μg/kg],差异具有统计学意义(t=3.181,P<0.05),HDCP组脐血 Cu[(21.58±24.42)μg/kg]显著高于正常组脐血[(8.28±4.21)μg/kg],差异具有统计学意义(t=-2.882,P<0.05).正常组与各个疾病组Cr分布特征相同:脐血>母血>胎盘.GDM组[(0.32±0.24)μg/kg]与HDCP合并GDM组[(0.30±0.18)μg/kg]胎盘Cr含量显著低于正常组胎盘[(0.50±0.27)μg/kg],差异均有统计学意义(t=2.197、2.665,均P<0.05),HDCP 组[(3.49±1.37)μg/kg]与 HDCP 合并 GDM 组[(2.79±0.49)μg/kg]脐血 Cr 含量显著高于正常组脐血[(1.15±1.68)μg/kg],差异均有统计学意义(t=-4.524、-2.843,均P<0.05).结论 GDM和HDCP合并GDM的发生改变了 Cu在母胎体系中的分布特征,HDCP和GDM影响了 Cu和Cr的胎盘代谢和转运,从而可能增加胎儿的健康风险.
目的 研究不同妊娠期合并症对胎盘屏障功能的影响.方法 选取2021年5月至2022年5月云南省第一人民医院产科住院分娩的62例孕妇为研究对象,根据孕妇健康状况分为妊娠期糖尿病组(n=16),妊娠期高血压疾病组(n=16)和正常孕产妇组(n=30),采用电感耦合等离子质谱法(ICP-MS)测定并比较各组母血、脐血和胎盘中铅水平.结果 正常孕产妇组和妊娠期糖尿病组铅的分布为胎盘最高、母血次之、脐血最低,妊娠期高血压疾病组铅分布为胎盘最高、脐血次之、母血最低.与正常孕产妇组比较,妊娠期糖尿病组母血、胎盘及脐血铅水平更高,妊娠期高血压疾病组母血、脐血铅水平更高,差异有统计学意义(P<0.05).妊娠期糖尿病组(75.0%)和妊娠期高血压疾病组(62.5%)铅胎盘屏障率低于正常孕产妇组(76.6%).结论 妊娠期合并症可使胎盘屏障功能降低.
Abstract Purpose To evaluate the levels and differences of trace elements (Zn, Cu, Fe, Mn, Ni, Cr) in maternal-fetal systems (maternal blood, placenta, umbilical cord blood) of different healthy states. To analyze the influence of pregnancy disease on the distribution of trace elements between the mother and fetus. Methods Maternal, placental and umbilical blood samples were collected from 140 parturients (60 in the normal group, 40 in the HDCP group and 40 in the GDM group). The contents of trace elements in paired samples were determined by inductively coupled plasma–mass spectrometry (ICP–MS). SPSS software was used to analyze the differences in trace element levels in matched samples of each group. Results The distribution of Fe content in the normal group was as follows: umbilical cord blood > maternal blood > placenta (p < 0.001). Although the distribution characteristics of Fe in the HDCP group and GDM group were the same as those in the normal group, there was no significant difference in Fe content between maternal and umbilical cord blood (p > 0.05). In addition, the levels of Fe in maternal blood, placental blood and umbilical cord blood in the HDCP group were higher than those in the normal control group (p < 0.05). The distribution characteristics of Mn content in the HDCP group and GDM group were placenta > umbilical cord blood > maternal blood. There were significant differences in Mn content between the placenta and maternal and umbilical cord blood (p < 0.001). The distribution characteristics of Mn content in the HDCP group and GDM group were placenta > umbilical cord blood > maternal blood. There were significant differences in the Mn content between the placenta, maternal blood and umbilical blood in the HDCP group (p < 0.05). Only the Mn content between the placenta and maternal blood was significantly different in the GDM group (p < 0.001). In addition, the content of Cr in the placenta and umbilical blood of the HDCP group was higher than that of the normal group (p < 0.05). The content of Ni in the cord blood of the HDCP group and GDM group was higher than that of the normal group (p < 0.05). Conclusion HDCP and GDM affect the transport of Fe, Ni and Cr from the placenta to the fetus. In addition, the occurrence of GDM also changes the distribution of Fe and Mn in the maternal-fetal system (maternal blood, placenta and umbilical cord blood).
SUMMARY Extraembryonic endoderm stem (XEN) cell lines can be derived and maintained in vitro and reflect the primitive endoderm cell lineage. SOX17 is thought to be required for the derivation and maintenance of mouse XEN cell lines. Here we have re-evaluated this requirement for SOX17. We derived multiple SOX17-deficient XEN cell lines from preimplantation embryos of a SOX17-Cre knockout strain and chemically converted multiple SOX17-deficient embryonic stem cell lines into XEN cell lines by transient culturing with retinoic acid and Activin A. We confirmed the XEN profile of SOX17-deficient cell lines by immunofluorescence with various markers, by NanoString gene expression analyses, and by their contribution to the extraembryonic endoderm of chimeric embryos produced by injecting these cells into blastocysts. Thus, SOX17 is not required for the derivation and maintenance of XEN cell lines.
BACKGROUND:Nickel (Ni) may accumulate in the human body and has biological toxicity and carcinogenicity. Ni has an extensive impact on the health of pregnant women and fetuses during gestation.AIM:To evaluate Ni exposure in pregnant women in Kunming, Yunnan Province, China; to describe the distribution of Ni in the maternal-fetal system and placental barrier function; and to investigate the effect of Ni exposure on fetal health in mothers with pregnancy complications.METHODS:Seventy-two pregnant women were selected using a case-control design. The women were divided into two groups: The control group (no disease; n = 29) and the disease group [gestational diabetes (GDM), hypertensive disorder complicating pregnancy (HDCP), or both; n = 43]. The pregnant women in the disease group were further divided as follows: 14 cases with GDM (GDM group), 13 cases with HDCP (HDCP group) and 16 cases with both GDM and HDCP (disease combination group). Basic information on the pregnant women was collected by questionnaire survey. Maternal blood, placenta blood and cord blood were collected immediately after delivery. The Ni content in paired samples was determined using inductively coupled plasma mass spectrometry.RESULTS:Compared to the control group, age was higher and body mass index was greater in pregnant women in the disease groups (28.14 ± 2.54 vs 28.42 ± 13.89, P < 0.05; 25.90 ± 3.86 vs 31.49 ± 5.30, P < 0.05). The birth weights of newborns in the HDCP group and the control group were significantly different (2.52 ± 0.74 vs 3.18 ± 0.41, P < 0.05). The content of Ni in umbilical cord blood in the entire disease group was higher than that in the control group (0.10 ± 0.16 vs 0.05 ± 0.07, P < 0.05).CONCLUSION:In the maternal-fetal system of women with pregnancy complications, the barrier effect of the placenta against Ni is weakened, thus affecting healthy growth of the fetus in the uterus.
目的 分析镍对孕妇妊娠期疾病发病和妊娠结局的影响.方法 选取2015年1月-2018年12月在云南省第一人民医院产科住院分娩的71例孕妇,根据孕妇健康状况分为对照组(28例)和疾病组(43例),疾病组孕妇又分为妊娠期糖尿病组(14例,妊娠期糖尿病)、妊娠期高血压疾病组(14例,妊娠期高血压疾病)及妊娠期疾病合并组(15例,妊娠期糖尿病合并妊娠期高血压疾病).收集孕妇基本特征和新生儿出生信息,分娩后立即采集母血、胎盘及脐血样本,检测镍水平.结果 对照组母血、胎盘及脐血镍水平分别为(0.08±0.13) μg/L、(0.04±0.06) μg/L及(0.05±0.07) μg/L.疾病组母血、胎盘及脐血镍水平分别为(0.05±0.07) μg/L、(0.06±0.07) μg/L及(0.11±0.20)μg/L.两组母血、胎盘及脐血镍水平比较差异均无统计学意义(t=0.889,P=0.380;t=1.334,P=0.187;t=-1.633,P=0.108).妊娠期糖尿病组母血、胎盘及脐血镍水平分别为(0.03±0.04) μg/L、(0.04±0.07) μg/L及(0.11±0.29) μg/L.妊娠期高血压疾病组母血、胎盘及脐血镍水平分别为(0.06±0.06)μg/L、(0.06±0.05) μg/L及(0.15±0.20) μg/L.妊娠期疾病合并组母血、胎盘及脐血镍水平分别为(0.07±0.09) μg/L、(0.08±0.07) μg/L及(0.06±0.05) μg/L.妊娠期高血压疾病组和对照组脐血镍水平比较差异有统计学意义(t=-2.490,P=0.017).对照组、疾病组母血镍水平/脐血镍水平>1的比例分别为85.7%和60.5%.妊娠期糖尿病组、妊娠期高血压疾病组及妊娠期疾病合并组母血镍水平/脐血镍水平>1的比例分别为71.4%、50.0%及60.0%.结论 镍可通过胎盘转移至胎儿,有破坏胎盘组织的潜力.孕妇长期暴露于镍是发生妊娠期疾病和胎儿宫内生长受限的风险因素.
目的 分析砷(As)从母体转运到新生儿的规律及胎盘屏障与妊娠期糖尿病(GDM)和妊娠期高血压(HDCP)的关系.方法 选取正常妊娠的产妇作为对照组(n=29),合并有妊娠期疾病的产妇作为观察组(n=78),并根据疾病类型将观察组再分为GDM组(n=27)、HDCP组(n=32)及GDM合并HDCP(GDM+HDCP)组(n=19).收集每组产妇的外周血 、胎盘及脐血,检测并比较各样品间As水平,比较观察组与对照组各样品间As水平.以每个产妇母血As/脐血As>1来衡量胎盘屏障功能,以每组母血As/脐血As>1的产妇比例来衡量疾病对胎盘屏障功能的影响.结果 对照组孕妇母血As水平高于脐血,差异有统计学意义(P<0.01);对照组母血As水平高于GDM组 、HDCP组及GDM+HDCP组,差异均有统计学意义(P<0.01);对照组胎盘As水平明显高于GDM组 、HDCP组及GDM&HDCP组(P<0.05);母血As/脐血As>1的孕妇比例:对照组82.76% 、观察组50.00% 、GDM组48.15% 、HDCP组53.12% 、GDM&HDCP组47.37%.结论 健康孕妇胎盘屏障功能较好,可阻止As向胎儿转运,母血中低As水平可能促进了母体GDM和HDCP的发生 、发展.