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1.
Artigo em Inglês | MEDLINE | ID: mdl-34200176

RESUMO

Prenatal exposure to bisphenol A (BPA) may increase the risk of abnormal birth outcomes, and DNA methylation might mediate these adverse effects. This study aimed to investigate the effects of maternal BPA exposure on maternal and fetal DNA methylation levels and explore whether epigenetic changes are related to the associations between BPA and low birth weight. We collected urine and blood samples originating from 162 mother-infant pairs in a Taiwanese cohort study. We measured DNA methylation using the Illumina Infinium HumanMethylation 450 BeadChip in 34 maternal blood samples with high and low BPA levels based on the 75th percentile level (9.5 µg/g creatinine). Eighty-seven CpGs with the most differentially methylated probes possibly interacting with BPA exposure or birth weight were selected using two multiple regression models. Ingenuity pathway analysis (IPA) was utilized to narrow down 18 candidate CpGs related to disease categories, including developmental disorders, skeletal and muscular disorders, skeletal and muscular system development, metabolic diseases, and lipid metabolism. We then validated these genes by pyrosequencing, and 8 CpGs met the primer design score requirements in 82 cord blood samples. The associations among low birth weight, BPA exposure, and DNA methylation were analyzed. Exposure to BPA was associated with low birth weight. Analysis of the epigenome-wide findings did not show significant associations between BPA and DNA methylation in cord blood of the 8 CpGs. However, the adjusted odds ratio for the dehydrogenase/reductase member 9 (DHRS9) gene, at the 2nd CG site, in the hypermethylated group was significantly associated with low birth weight. These results support a role of BPA, and possibly DHRS9 methylation, in fetal growth. However, additional studies with larger sample sizes are warranted.


Assuntos
Metilação de DNA , Efeitos Tardios da Exposição Pré-Natal , Compostos Benzidrílicos/toxicidade , Peso ao Nascer , Estudos de Coortes , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Exposição Materna/efeitos adversos , Fenóis , Projetos Piloto , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Taiwan/epidemiologia
2.
Sci Total Environ ; 618: 635-644, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29055577

RESUMO

The contamination of a clouding agent with di(2-ethylhexyl) phthalate (DEHP), a substitute emulsifier-containing compound used in a variety of foods was announced on May 23, 2011. The aims of this study were as follows (1) compare the urine phthalates (PAE) metabolites concentration and estimate the daily intake (DI) of PAEs in pregnant women before and after the tainted food scandal and (2) examine the effect of relatively high PAEs exposure on birth outcome. One-hundred twelve pregnant women in Northern Taiwan participated in this study from March to December 2010, i.e., before the tainted food scandal. After the tainted food scandal, we collected 69, 73, and 180 urine specimens (January 2013 to August 2014) from women whom were in their first, second, and third trimesters of pregnancy, respectively. We measure urinary DEHP metabolite concentrations to estimate the DI of DEHP and the hazard quotient (HQ) of subjects. This was the first study to assess the effects of DEHP-tainted food scandal exposure in pregnant women across the three trimesters of pregnancy. After the tainted food report, the concentrations of urine PAE metabolite were significantly decreased, especially those of DEHP metabolites. Based on different reference limit values, the percentages of pregnant women whose HQDEHP value exceeded the limit ranged from 0.53% to 8.93%. Despite this low frequency, the higher ΣPAE exposure during the second trimester may significantly increase the risk of relatively low birth height compared to the lower exposure group (ß=-0.63 (-1.20 to -0.06)). Our results support the hypothesis that exposure to relatively high concentrations of DEHP in pregnant Taiwanese women may have an adverse effect on birth outcomes. The percentage of subjects whose exposure level exceeded the exposure limit was low; however, high PAEs exposure appears to be significantly associated with birth outcomes. Therefore, we suggest that reference dose for PAEs should be revised.


Assuntos
Exposição Dietética , Dietilexilftalato/análise , Contaminação de Alimentos , Ácidos Ftálicos/urina , Adulto , Feminino , Humanos , Gravidez , Taiwan
3.
Sci Total Environ ; 612: 1373-1379, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-28898944

RESUMO

BACKGROUND: Arsenic exposure is a global health concern. Several studies have focused on chronic arsenic exposure in adults; however, limited data are available regarding the potential adverse effects of prenatal exposure on fetuses and neonates. OBJECTIVES: To assess which time point maternal arsenic exposure may influence the fetus during pregnancy and birth outcomes. METHODS: In this study, total arsenic concentrations were analyzed in urine samples collected from 130 women with singleton pregnancies (22-45years old) in Taiwan from March to December of 2010. All fetal biometric measurements in each trimester period and birth outcomes at delivery were obtained. We applied a generalized estimating equation model and multivariate regression models to evaluate the associations between maternal urinary total arsenic (UtAs) exposure during pregnancy, fetal biometric measurements, and neonatal birth outcomes. RESULTS: We observed statistically significant correlations between maternal UtAs levels and the fetal biparietal diameter over all three trimesters (ß=-1.046mm, p<0.05). Multiple regression analyses showed a negative association between maternal UtAs levels and chest circumference in the first trimester (ß=-0.721cm, p<0.05), and second-trimester UtAs exposure was associated with decreases in birth weight (ß=-173.26g, p<0.01), head circumference (ß=-0.611cm, p<0.05), and chest circumference (ß=-0.654cm, p<0.05). Dose-response relationships were also observed for maternal UtAs exposure and birth outcomes. CONCLUSIONS: We identified a negative relationship between maternal UtAs levels during pregnancy, fetal development, and neonatal birth outcomes. These findings should be confirmed in future studies with large sample sizes.


Assuntos
Arsênio/urina , Desenvolvimento Fetal , Exposição Materna/efeitos adversos , Adulto , Peso ao Nascer , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Pessoa de Meia-Idade , Análise Multivariada , Gravidez , Análise de Regressão , Taiwan , Adulto Jovem
5.
ACS Nano ; 11(8): 8167-8177, 2017 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-28721719

RESUMO

Circulating fetal nucleated cells (CFNCs) in maternal blood offer an ideal source of fetal genomic DNA for noninvasive prenatal diagnostics (NIPD). We developed a class of nanoVelcro microchips to effectively enrich a subcategory of CFNCs, i.e., circulating trophoblasts (cTBs) from maternal blood, which can then be isolated with single-cell resolution by a laser capture microdissection (LCM) technique for downstream genetic testing. We first established a nanoimprinting fabrication process to prepare the LCM-compatible nanoVelcro substrates. Using an optimized cTB-capture condition and an immunocytochemistry protocol, we were able to identify and isolate single cTBs (Hoechst+/CK7+/HLA-G+/CD45-, 20 µm > sizes > 12 µm) on the imprinted nanoVelcro microchips. Three cTBs were polled to ensure reproducible whole genome amplification on the cTB-derived DNA, paving the way for cTB-based array comparative genomic hybridization (aCGH) and short tandem repeats analysis. Using maternal blood samples collected from expectant mothers carrying a single fetus, the cTB-derived aCGH data were able to detect fetal genders and chromosomal aberrations, which had been confirmed by standard clinical practice. Our results support the use of nanoVelcro microchips for cTB-based noninvasive prenatal genetic testing, which holds potential for further development toward future NIPD solution.


Assuntos
Hibridização Genômica Comparativa/métodos , DNA/química , Adolescente , Adulto , Feminino , Testes Genéticos , Humanos , Imuno-Histoquímica , Masculino , Trissomia/genética , Trofoblastos/metabolismo , Adulto Jovem
6.
Sci Total Environ ; 607-608: 1126-1135, 2017 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-28724251

RESUMO

Prenatal exposure to phenols, phthalates (PAEs), and organophosphate (OP) pesticides may increase the risk of abnormal birth outcomes. However, many previous studies have examined exposure to a limited number of chemical classes or exposure profiles limited to a specific stage of pregnancy. This study aims to characterize the concurrent exposure scenario throughout pregnancy by simultaneously monitoring internal doses of several endocrine-disrupting compounds (EDCs), including 2 phenols (nonylphenol (NP) and bisphenol A (BPA)), 9 PAEs, and 6 OP pesticide metabolites and to assess the relationships between concurrent exposure to EDCs and infant birth weight, length, and head and chest circumference. One hundred and sixty two women provided three spot urine samples at approximately 11 and 26weeks gestation and at delivery. We applied multivariable linear regression and ridge regression models to estimate the effects of separate and correlated exposures. Multivariable linear regression models revealed that women with short birth-length infants had significantly higher urinary second-trimester NP levels (50th percentile, 5.03µg/g creatinine) (ß=-0.47cm; 95% CI=-0.93 to -0.01). Similarly significant relationships were observed between second-trimester mono-methyl phthalate (MMP) exposure and short birth length, second-trimester ΣPAEs and short birth length, second-trimester ΣPAEs exposure and reduced head and chest circumference, second-trimester diethylphosphate (DEP) exposure and reduced birth weight and length, and second-trimester ΣDEPs exposure and short birth length. Women with urinary BPA above the 75th percentile or ΣPAEs levels above the 50th percentile in the third trimester had infants with significantly reduced head circumference. These observations suggest that the second trimester may be the critical stage of susceptibility for fetal development. In ridge regression models, for which women with fewer measures for exposure to NP, BPA, MMP, ΣPAEs, DEP and ΣDEPs simultaneously were available, no relationships were found with infant size at birth. Additional studies with larger sample sizes are warranted.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Exposição Materna/efeitos adversos , Organofosfatos/efeitos adversos , Fenóis/efeitos adversos , Ácidos Ftálicos/efeitos adversos , Peso ao Nascer , Estatura , Estudos de Coortes , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Humanos , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Taiwan
8.
Stem Cells Transl Med ; 5(11): 1473-1484, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27405780

RESUMO

: Liver fibrosis represents the end stage of chronic liver inflammatory diseases and is defined by the abnormal accumulation of extracellular matrix in the liver. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension. Liver transplantation has been the most effective treatment for these diseases, but the procedure is limited by the shortage of suitable donors. Mesenchymal stromal cells (MSCs) have shown great potential in the treatment of chronic inflammatory diseases associated with fibrosis. This study aimed to evaluate the therapeutic effect of MSC-based cell transplantation as an alternative treatment for liver fibrosis. A CD34-positive subpopulation of human placental amnion membrane-derived stem/progenitor cells (CD34+ AMSPCs) was isolated through the depletion of CD34-negative stromal fibroblasts (CD34- AMSFCs) facilitated by CD34 fluorescence-activated cell sorting, enriched and expanded ex vivo. These cells express pluripotency markers and demonstrate multidirectional differentiation potentials. Comparative analysis was made between CD34+ AMSPCs and CD34- AMSFCs in terms of the expressions of stemness surface markers, embryonic surface antigens, and multilineage differentiation potentials. A mouse model of liver fibrosis was established by thioacetamide (TAA) administration. When injected into the spleen of TAA-injured mice, human placental amnion membrane-derived MSCs (hAM-MSCs) can engraft into the injury site, ameliorate liver fibrosis, and restore liver function, as shown by pathological and blood biochemical analysis and downregulated gene expressions associated with liver damage. CD34+ AMSPCs represent a more primitive subset of hAM-MSCs and could be a suitable candidate with a potentially better safety profile for cell-based therapy in treatment of liver diseases associated with fibrosis. SIGNIFICANCE: In this study, a CD34+ subpopulation of stem/progenitor cells derived from neonatal placental amnion membrane, denoted as CD34+ AMSPCs, were identified, enriched, and characterized. These cells are highly proliferative, express mesenchymal stromal cells and pluripotent stem cell markers, and demonstrate multidirectional differentiation potentials, indicating their promising application in clinical regenerative therapies. CD34+ AMSPC transplantation ameliorated liver fibrosis in mice with drug-induced liver injury. These cells represent a potential therapeutic agent for treating liver diseases associated with fibrosis.

9.
Sci Rep ; 6: 20725, 2016 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-26869526

RESUMO

Annual influenza vaccination is recommended, but its efficacy in dialysis population is still controversial. Here we aimed to compare the dynamic changes of immune response between various influenza vaccination protocols in hemodialysis patients. A 18-week open label, non-randomized, controlled trial was conducted during 2011-2012. The efficacy between unvaccinated, one- and two-dose regimens were evaluated in 175 hemodialysis patients. Immunogenic profiles were assessed by hemagglutination-inhibition assays. At 3-9 weeks post-vaccination, antibody responses were similar between the one- and two-dose regimens, while the seroprotection rates (antibody titer ≥1:40) for influenza A were 55.6-82.5% in the adult (18-60 years) and 33.3-66.7% in the elderly (>60 years). Meanwhile, the seroprotection rates for influenza B were low (4.0-25.0%). By 18 weeks post-vaccination, the seroprotection rates for influenza A and B declined (0.0-33.3%) in both the adult and elderly receiving one- or two-dose regimens. Of dialysis patients, at most 2.4% developed moderate to severe adverse effects(myalgia and headache) after vaccination. In conclusion, the two-dose regimen could not improve immune responses than the one-dose regimen in hemodialysis patients; meanwhile the induced protective antibodies of both regimens could not be maintained for more than 4 months. Modification of current influenza vaccination strategy in dialysis population should be re-considered.


Assuntos
Imunização Secundária , Influenza Humana/imunologia , Diálise Renal , Vacinação , Adulto , Relação Dose-Resposta Imunológica , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Resultado do Tratamento , Vacinação/efeitos adversos
10.
Mol Cell Biol ; 36(1): 197-209, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26503785

RESUMO

Human chorionic gonadotropin (hCG) is composed of a common α subunit and a placenta-specific ß subunit. Importantly, hCG is highly expressed in the differentiated and multinucleated syncytiotrophoblast, which is formed via trophoblast cell fusion and stimulated by cyclic AMP (cAMP). Although the ubiquitous activating protein 2 (AP2) transcription factors TFAP2A and TFAP2C may regulate hCGß expression, it remains unclear how cAMP stimulates placenta-specific hCGß gene expression and trophoblastic differentiation. Here we demonstrated that the placental transcription factor glial cells missing 1 (GCM1) binds to a highly conserved promoter region in all six hCGß paralogues by chromatin immunoprecipitation-on-chip (ChIP-chip) analyses. We further showed that cAMP stimulates GCM1 and the CBP coactivator to activate the hCGß promoter through a GCM1-binding site (GBS1), which also constitutes a previously identified AP2 site. Given that TFAP2C may compete with GCM1 for GBS1, cAMP enhances the association between the hCGß promoter and GCM1 but not TFAP2C. Indeed, the hCG-cAMP-protein kinase A (PKA) signaling pathway also stimulates Ser269 and Ser275 phosphorylation of GCM1, which recruits CBP to mediate GCM1 acetylation and stabilization. Consequently, hCG stimulates the expression of GCM1 target genes, including the fusogenic protein syncytin-1, to promote placental cell fusion. Our study reveals a positive feedback loop between GCM1 and hCG regulating placental hCGß expression and cell differentiation.


Assuntos
Diferenciação Celular/fisiologia , Gonadotropina Coriônica Humana Subunidade beta/metabolismo , Gonadotropina Coriônica/metabolismo , Neuropeptídeos/metabolismo , Proteínas Nucleares/metabolismo , Placenta/metabolismo , Fatores de Transcrição/metabolismo , Diferenciação Celular/genética , Linhagem Celular , Gonadotropina Coriônica/genética , Gonadotropina Coriônica Humana Subunidade beta/genética , Proteínas de Ligação a DNA , Feminino , Humanos , Neuroglia/metabolismo , Neuropeptídeos/genética , Proteínas Nucleares/genética , Gravidez , Regiões Promotoras Genéticas/genética , Fatores de Transcrição/genética
11.
Taiwan J Obstet Gynecol ; 54(5): 554-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26522110

RESUMO

OBJECTIVE: To examine the association of antenatal renal pelvic dilatation observed on midtrimester ultrasound screening with the presence of hydronephrosis in newborn infants. MATERIALS AND METHODS: The records of patients who received fetal ultrasound examination at 18-28 weeks' gestation from May 2008 to March 2012 were retrospectively reviewed. A fetal renal pelvic anterior-posterior (AP) diameter > 4 mm was considered abnormal and ≤ 4 mm was considered normal. On postnatal ultrasound, a renal pelvic AP diameter > 3 mm was considered to indicate hydronephrosis and ≤ 3 mm was considered normal. The association of postnatal hydronephrosis with prenatal pelvic AP diameter was determined using binary logistic regression analysis. RESULTS: The study comprised 1310 newborn infants: 684 (52.2%) male and 626 (47.8%) female. Multivariate analysis showed a right or left prenatal AP renal pelvic diameter > 4 mm was associated with a higher risk of postnatal hydronephrosis compared with a right and left prenatal AP renal pelvic diameter ≤ 4 mm. Boys had a higher risk for postnatal hydronephrosis than girls (odds ratio = 2.42, p < 0.05). CONCLUSION: An antenatal renal pelvic AP diameter > 4 mm on midtrimester ultrasound is predictive of postnatal hydronephrosis.


Assuntos
Hidronefrose/epidemiologia , Pelve Renal/diagnóstico por imagem , Rim/diagnóstico por imagem , Segundo Trimestre da Gravidez , Ultrassonografia Pré-Natal/métodos , Feminino , Seguimentos , Idade Gestacional , Humanos , Hidronefrose/diagnóstico por imagem , Incidência , Recém-Nascido , Rim/embriologia , Pelve Renal/embriologia , Masculino , Tamanho do Órgão , Gravidez , Estudos Retrospectivos , Taiwan/epidemiologia
12.
PLoS One ; 10(9): e0138145, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26367380

RESUMO

OBJECTIVE: Fetal nuchal translucency (NT) thickness is an important marker for prenatal screening; however, studies focusing on the correlation between maternal trace element levels and NT thickness are limited. The aim of this study was to evaluate maternal trace element levels during the first trimester and to investigate the association between maternal trace element levels and fetal NT thickness. METHODS: In total, 113 samples were obtained from singleton pregnant women. Maternal plasma samples were collected in the first trimester of gestation. Plasma trace element levels were measured using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Nuchal translucency thickness was measured using ultrasonography at 10-14 weeks of gestation. RESULTS: We found that maternal plasma potassium (K) levels had a significant negative correlation with both NT (r = -0.230, p < 0.05) and NT Multiples of the Median (NT MoM) (r = -0.206, p < 0.05). After adjustment for potential confounders, log-transformed maternal plasma potassium levels in the first trimester were significantly associated with fetal NT (NT MoM: ß = -0.68, p < 0.05; NT: ß = -1.20, p < 0.01). Although not statistically significant, the As, Hg and Pb levels in maternal plasma were positively correlated with NT, and the Mg, Cu, Zn, Na and Ca levels were negatively correlated with NT. CONCLUSION: Maternal plasma K levels during the first trimester appeared to be associated with NT thickness. The essential elements tended to decrease NT thickness, and non-essential elements tended to increase it.


Assuntos
Medição da Translucência Nucal , Primeiro Trimestre da Gravidez/sangue , Gravidez/sangue , Oligoelementos/sangue , Feminino , Humanos
13.
Hepatology ; 62(2): 375-86, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25851052

RESUMO

UNLABELLED: The efficacy and safety of maternal tenofovir disoproxil fumarate (TDF) in reducing mother-to-infant hepatitis B virus (HBV) transmissions is not clearly understood. We conducted a prospective, multicenter trial and enrolled 118 hepatitis B surface antigen (HBsAg)- and hepatitis B e antigen-positive pregnant women with HBV DNA ≥7.5 log10 IU/mL. The mothers received no medication (control group, n = 56, HBV DNA 8.22 ± 0.39 log10 IU/mL) or TDF 300 mg daily (TDF group, n = 62, HBV DNA 8.18 ± 0.47 log10 IU/mL) from 30-32 weeks of gestation until 1 month postpartum. Primary outcome was infant HBsAg at 6 months old. At delivery, the TDF group had lower maternal HBV DNA levels (4.29 ± 0.93 versus 8.10 ± 0.56 log10 IU/mL, P < 0.0001). Of the 121/123 newborns, the TDF group had lower rates of HBV DNA positivity at birth (6.15% versus 31.48%, P = 0.0003) and HBsAg positivity at 6 months old (1.54% versus 10.71%, P = 0.0481). Multivariate analysis revealed that the TDF group had lower risk (odds ratio = 0.10, P = 0.0434) and amniocentesis was associated with higher risk (odds ratio 6.82, P = 0.0220) of infant HBsAg positivity. The TDF group had less incidence of maternal alanine aminotransferase (ALT) levels above two times the upper limit of normal for ≥3 months (3.23% versus 14.29%, P = 0.0455), a lesser extent of postpartum elevations of ALT (P = 0.007), and a lower rate of ALT over five times the upper limit of normal (1.64% versus 14.29%, P = 0.0135) at 2 months postpartum. Maternal creatinine and creatinine kinase levels, rates of congenital anomaly, premature birth, and growth parameters in infants were comparable in both groups. At 12 months, one TDF-group child newly developed HBsAg positivity, presumably due to postnatal infection and inefficient humoral responses to vaccines. CONCLUSIONS: Treatment with TDF for highly viremic mothers decreased infant HBV DNA at birth and infant HBsAg positivity at 6 months and ameliorated maternal ALT elevations. (Hepatology 2015;62:375-386.


Assuntos
Adenina/análogos & derivados , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Organofosfonatos/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Resultado da Gravidez , Adenina/uso terapêutico , Adulto , DNA Viral/análise , Feminino , Seguimentos , Idade Gestacional , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/transmissão , Humanos , Recém-Nascido , Masculino , Idade Materna , Análise Multivariada , Seleção de Pacientes , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , Estudos Prospectivos , Valores de Referência , Medição de Risco , Taiwan , Tenofovir , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Adulto Jovem
14.
Stem Cells Dev ; 24(15): 1740-50, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-25923707

RESUMO

Human neural stem cells (NSCs) are particularly valuable for the study of neurogenesis process and have a therapeutic potential in treating neurodegenerative disorders. However, current progress in the use of human NSCs is limited due to the available NSC sources and the complicated isolation and culture techniques. In this study, we describe an efficient method to isolate and propagate human NSCs from the amniotic fluid with diagnosed neural tube defects (NTDs), specifically, anencephaly. These amniotic fluid-derived NSCs (AF-NSCs) formed neurospheres and underwent long-term expansion in vitro. In addition, these cells showed normal karyotypes and telomerase activity and expressed NSC-specific markers, including Nestin, Sox2, Musashi-1, and the ATP-binding cassette G2 (ABCG2). AF-NSCs displayed typical morphological patterns and expressed specific markers that were consistent with neurons, astrocytes, oligodendrocytes, and dopaminergic neurons after proper induction conditions. Furthermore, grafted AF-NSCs improved the physiological functions in a rat stroke model. The ability to isolate and bank human NSCs from this novel source provides a unique opportunity for translational studies of neurological disorders.


Assuntos
Líquido Amniótico/metabolismo , Células-Tronco Neurais/metabolismo , Defeitos do Tubo Neural/metabolismo , Adulto , Animais , Antígenos de Diferenciação/metabolismo , Feminino , Xenoenxertos , Humanos , Células-Tronco Neurais/patologia , Células-Tronco Neurais/transplante , Defeitos do Tubo Neural/diagnóstico , Defeitos do Tubo Neural/patologia , Gravidez , Ratos , Ratos Sprague-Dawley , Transplante de Células-Tronco , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/terapia
15.
Environ Res ; 137: 215-21, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25575372

RESUMO

Prenatal exposure and the health effects of that exposure have been intensively studied for a variety of environmental pollutants and trace elements. However, few studies have compared susceptibilities among the three trimesters of gestation. Manganese (Mn) is a naturally occurring and abundant trace element in the environment. Although the effects of Mn on animals are well documented, knowledge of the effects of Mn exposure on pregnant women and fetuses remains limited. A longitudinal study was conducted by collecting blood samples during all three trimesters, and Mn exposure was completely characterized during gestation. The aims of this study were to examine the effects of maternal Mn exposure on neonatal birth outcomes and to explore the critical stage of these effects. In total, 38, 76 and 76 samples were obtained from singleton pregnant women in their first, second and third trimesters, respectively. The cohort of pregnant women was selected at a medical center in northern Taiwan. Erythrocyte samples were collected during the first, second and third trimesters of gestation. Erythrocyte Mn concentrations were measured by inductively coupled plasma mass spectrometry. Neonatal birth outcomes were evaluated immediately after delivery. A multivariate regression model was used to determine the associations between maternal Mn levels in erythrocytes in each trimester and neonatal birth outcomes. The geometric mean concentrations of Mn were 2.93 µg/dL, 3.96 µg/dL and 4.41 µg/dL in the first, second and third trimesters, respectively. After adjusting for potential confounders, a consistently negative association was found between maternal Mn levels throughout the three trimesters and birth outcomes. Log-transformed Mn levels in maternal erythrocytes in the second trimester were significantly associated with neonatal birth weight, head and chest circumferences, respectively (ß=-556.98 g, p=0.038; ß=-1.87 cm, p=0.045; ß=-2.74 cm, p=0.024). Despite the limited sample size in the first trimester, negative effects of maternal Mn levels on birth weight (ß=-1108.95 g, p<0.01) and chest circumference (ß=-4.40 cm, p=0.019) were also observed.


Assuntos
Poluentes Ambientais/sangue , Feto/metabolismo , Manganês/sangue , Exposição Materna , Resultado da Gravidez/epidemiologia , Adulto , Antropometria , Índice de Apgar , Eritrócitos/química , Feminino , Humanos , Recém-Nascido , Estudos Longitudinais , Masculino , Espectrometria de Massas , Gravidez , Trimestres da Gravidez , Análise de Regressão , Taiwan/epidemiologia
16.
Stem Cells Transl Med ; 3(10): 1138-47, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25154783

RESUMO

Preclinical studies of amniotic fluid-derived cell therapy have been successful in the research of neurodegenerative diseases, peripheral nerve injury, spinal cord injury, and brain ischemia. Transplantation of human amniotic fluid stem cells (AFSCs) into rat brain ventricles has shown improvement in symptoms of Parkinson's disease and also highlighted the minimal immune rejection risk of AFSCs, even between species. Although AFSCs appeared to be a promising resource for cell-based regenerative therapy, AFSCs contain a heterogeneous pool of distinct cell types, rendering each preparation of AFSCs unique. Identification of predictive markers for neuron-prone AFSCs is necessary before such stem cell-based therapeutics can become a reality. In an attempt to identify markers of AFSCs to predict their ability for neurogenesis, we performed a two-phase study. In the discovery phase of 23 AFSCs, we tested ZNF521/Zfp521, OCT6, SOX1, SOX2, SOX3, and SOX9 as predictive markers of AFSCs for neural differentiation. In the validation phase, the efficacy of these predictive markers was tested in independent sets of 18 AFSCs and 14 dental pulp stem cells (DPSCs). We found that high expression of SOX9 in AFSCs is associated with good neurogenetic ability, and these positive correlations were confirmed in independent sets of AFSCs and DPSCs. Furthermore, knockdown of SOX9 in AFSCs inhibited their neuronal differentiation. In conclusion, the discovery of SOX9 as a predictive marker for neuron-prone AFSCs could expedite the selection of useful clones for regenerative medicine, in particular, in neurological diseases and injuries.


Assuntos
Líquido Amniótico/citologia , Biomarcadores/análise , Células-Tronco Embrionárias/citologia , Células-Tronco Neurais/citologia , Fatores de Transcrição SOX9/análise , Acetilcisteína , Western Blotting , Diferenciação Celular/fisiologia , Humanos , Neurogênese/fisiologia , Reação em Cadeia da Polimerase em Tempo Real , Transfecção
17.
PLoS One ; 9(8): e104245, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25148048

RESUMO

BACKGROUND: Nonylphenol (NP) has been proven as an endocrine disrupter and had the ability to interfere with the endocrine system. Though the health effects of NP on pregnant women and their fetuses are sustained, these negative associations related to the mechanisms of regulation for estrogen during pregnancy need to be further clarified. The objective of this study is to explore the association between maternal NP and hormonal levels, such as estradiol, testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH), and progesterone. METHODS: A pregnant women cohort was established in North Taiwan between March and December 2010. Maternal urine and blood samples from the first, second, and third trimesters of gestation were collected. Urinary NP concentration was measured by high-performance liquid chromatography coupled with fluorescent detection. A mixed-effects model using a generalised estimating equation (GEE) was applied to assess the associations between maternal NP concentration and plasma hormones throughout the three trimesters. RESULTS: In total, 162 singleton pregnant women completed this study through delivery. The geometric mean of creatinine-adjusted urinary NP concentrations were 4.27, 4.21, and 4.10 µg/g cre. in the first, second, and third trimesters respectively. A natural log-transformation of urinary NP concentrations were significantly associated with LH in the GEE model (ß = -0.23 mIU/ml, p<0.01). CONCLUSION: This perspective cohort study demonstrates that negative association occurs between maternal NP exposure and plasma LH levels. The estrogen-mimic effect of NP might influence the negative feedback on LH during pregnancy.


Assuntos
Disruptores Endócrinos/efeitos adversos , Hormônios Esteroides Gonadais/sangue , Exposição Materna/efeitos adversos , Fenóis/efeitos adversos , Adulto , Estudos de Coortes , Disruptores Endócrinos/urina , Feminino , Humanos , Pessoa de Meia-Idade , Fenóis/urina , Gravidez , Fatores de Risco , Taiwan , Adulto Jovem
19.
PLoS One ; 8(9): e76118, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24098771

RESUMO

Amniotic fluid stem cells (AFSCs) are multipotent stem cells that may be used in transplantation medicine. In this study, AFSCs established from amniocentesis were characterized on the basis of surface marker expression and differentiation potential. To further investigate the properties of AFSCs for translational applications, we examined the cell surface expression of human leukocyte antigens (HLA) of these cells and estimated the therapeutic effect of AFSCs in parkinsonian rats. The expression profiles of HLA-II and transcription factors were compared between AFSCs and bone marrow-derived mesenchymal stem cells (BMMSCs) following treatment with γ-IFN. We found that stimulation of AFSCs with γ-IFN prompted only a slight increase in the expression of HLA-Ia and HLA-E, and the rare HLA-II expression could also be observed in most AFSCs samples. Consequently, the expression of CIITA and RFX5 was weakly induced by γ-IFN stimulation of AFSCs compared to that of BMMSCs. In the transplantation test, Sprague Dawley rats with 6-hydroxydopamine lesioning of the substantia nigra were used as a parkinsonian-animal model. Following the negative γ-IFN response AFSCs injection, apomorphine-induced rotation was reduced by 75% in AFSCs engrafted parkinsonian rats but was increased by 53% in the control group after 12-weeks post-transplantation. The implanted AFSCs were viable, and were able to migrate into the brain's circuitry and express specific proteins of dopamine neurons, such as tyrosine hydroxylase and dopamine transporter. In conclusion, the relative insensitivity AFSCs to γ-IFN implies that AFSCs might have immune-tolerance in γ-IFN inflammatory conditions. Furthermore, the effective improvement of AFSCs transplantation for apomorphine-induced rotation paves the way for the clinical application in parkinsonian therapy.


Assuntos
Líquido Amniótico/citologia , Regulação da Expressão Gênica/genética , Antígenos HLA/metabolismo , Células-Tronco Multipotentes/metabolismo , Transtornos Parkinsonianos/terapia , Transplante de Células-Tronco/métodos , Animais , Primers do DNA/genética , Imunofluorescência , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Interferon gama/farmacologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Multipotentes/imunologia , Compostos Orgânicos , Oxidopamina/efeitos adversos , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/imunologia , Reação em Cadeia da Polimerase , Ratos , Ratos Sprague-Dawley , Substância Negra/efeitos dos fármacos , Substância Negra/patologia , Fatores de Transcrição/metabolismo
20.
Chemosphere ; 93(6): 1145-52, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23871597

RESUMO

BACKGROUND: The aim of this study was to explore the association between NP exposure and parity and their effect on neonatal birth weight. METHODS: A cohort of pregnant women was established in a medical center in North Taiwan. Urinary NP concentration was determined by high-performance liquid chromatography coupled with fluorescent detection and adjusted using creatinine. A multivariable regression model was fit to determine the association between the maternal NP level in each trimester and neonatal birth weight. The odds ratios (ORs) of infant birth weight below the 10th, 25th, and 50th percentiles, comparing pregnant women with the different NP exposure levels, was estimated using a logistic regression. RESULTS: Of the 162 pregnant women in the study, 99 were multiparas and 63 were primiparas. After adjusting for other covariates, the NP level in the second trimester had a significant association with birth weight in the primiparas (ß = -182.49 g, p value = 0.02). The OR of low infant birth weight, comparing pregnant women with different NP levels, was increased by decreasing the cutoff percentile for birth weight (OR = 1.18 for the 50th percentile, 2.12 for the 25th percentile, and 7.81 for the 10th percentile). The odds of primiparas with high NP level having a low neonatal birth weight increased to 3.87, 11.77, and 9.40 for the three different percentiles (p value < 0.05). CONCLUSION: Maternal NP exposure level is associated with an increased risk of low neonatal weight. Primiparas are especially at risk, and the second trimester of pregnancy may be the critical stage of exposure.


Assuntos
Peso ao Nascer , Poluentes Ambientais/sangue , Exposição Materna/estatística & dados numéricos , Paridade , Fenóis/sangue , Adulto , Estudos de Coortes , Feminino , Humanos , Lactente , Modelos Logísticos , Razão de Chances , Gravidez , Taiwan
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