Preeclampsia is associated with over-activation of the innate immune system in the placenta,in which toll-like receptor 4（TLR4） plays an essential part.With their potent anti-inflammatory effects,statins have been s...Preeclampsia is associated with over-activation of the innate immune system in the placenta,in which toll-like receptor 4（TLR4） plays an essential part.With their potent anti-inflammatory effects,statins have been suggested as potential prevention or treatment of preeclampsia,although evidence remains inadequate.Herewith,we investigated whether pravastatin could ameliorate preeclampsia-like phenotypes in a previously established lipopolysaccharide（LPS）-induced rat preeclampsia model,through targeting the TLR4/NF-κB pathway.The results showed that pravastatin reduced the blood pressure [maximum decline on gestational day（GD） 12,（101.33±2.49） mmHg vs.（118.3±1.37） mmHg,P〈0.05] and urine protein level [maximum decline on GD9,（3,726.23± 1,572.86） μg vs.（1,991.03 ±609.37）μg,P〈 0.05],which were elevated following LPS administration.Pravastatin also significantly reduced the rate of fetal growth restriction in LPS-treated rats（34.10% vs.8.99%,P〈0.05）.Further pathological analyses suggested a restoration of normal spiral artery remodeling in preeclampsia rats by pravastatin treatment.These effects of pravastatin were associated with decreased TLR4/NF-κB protein levels in the placenta and IL-6/MCP-1 levels in serum.Additionally,no obvious abnormalities in fetal liver,brain,and kidney were found after administration of pravastatin.These results provide supportive evidence for use of pravastatin in preventing preeclampsia.展开更多
Amoxicillin,a widely used antibiotic in human and veterinary pharmaceuticals,is now considered as an“emerging contaminant”because it exists widespreadly in the environment and brings a series of adverse outcomes.Cur...Amoxicillin,a widely used antibiotic in human and veterinary pharmaceuticals,is now considered as an“emerging contaminant”because it exists widespreadly in the environment and brings a series of adverse outcomes.Currently,systematic studies about the developmental toxicity of amoxicillin are still lacking.We explored the potential effects of amoxicillin exposure on pregnancy outcomes,maternal/fetal serum phenotypes,and fetal multiple organ development in mice,at different doses(75,150,300 mg/(kg·day))during late-pregnancy,or at a dose of 300 mg/(kg·day)during different stages(mid-/latepregnancy)and courses(single-/multi-course).Results showed that prenatal amoxicillin exposure(PAmE)had no significant infuence on the body weights of dams,but it could inhibit the physical development and reduce the survival rate of fetuses,especially during the midpregnancy.Meanwhile,PAmE altered multiple maternal/fetal serum phenotypes,especially in fetuses.Fetal multi-organ function results showed that PAmE inhibited testicular/adrenal steroid synthesis,long bone/cartilage and hippocampal development,and enhanced ovarian steroid synthesis and hepatic glycogenesis/lipogenesis,and the order of severity might be gonad(testis,ovary)>liver>others.Further analysis found that PAmE-induced multiorgan developmental and functional alterations had differences in stages,courses and fetal gender,and the most obvious changes might be in high-dose,late-pregnancy and multicourse,but there was no typical rule of a dose-response relationship.In conclusion,this study confirmed that PAmE could cause abnormal development and multi-organ function alterations,which deepens our understanding of the risk of PAmE and provides an experimental basis for further exploration of the long-term harm.展开更多
Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders(NDDs)in the offspring,especially in the case of drug exposure.However,little progress has been made to asse...Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders(NDDs)in the offspring,especially in the case of drug exposure.However,little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors.We collected and manually curated sub-pathways and pathways(sub-/pathways)and drug information to propose an analytical framework for predicting drug candidates.This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs.Further,specific and pleiotropic sub-/pathways/drugs were identified using entropy,and sex bias was analyzed in conjunction with logistic regression and random forest models.We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs,showing temporal or spatial changes across fetal development.Moreover,5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels.A user-friendly NDDP visualization website(https://ndd-lab.shinyapps.io/NDDP)was developed to allow researchers and clinicians to access and retrieve data easily.Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories.This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.展开更多
<strong>Objectiv</strong><strong>e</strong><strong>:</strong><span style="font-family:""><span style="font-family:Verdana;"> Children with fetal...<strong>Objectiv</strong><strong>e</strong><strong>:</strong><span style="font-family:""><span style="font-family:Verdana;"> Children with fetal alcohol spectrum disorder (FASD) are overrepresented in early intervention programs, foster care, special education, juvenile corrections, and mental health services. In this study, we examine relationships between FASD and non-FASD controls for adverse childhood experiences (ACEs), and neurodevelopmental disorders. </span><b><span style="font-family:Verdana;">Methods:</span> </b><span style="font-family:Verdana;">A chart review was conducted among patients seen at our clinic from 2010-2017 with data on FASD, ACEs, neurodevelopmental diagnoses, and foster or residential care placement available. </span><b><span style="font-family:Verdana;">Results:</span> </b><span style="font-family:Verdana;">Relative risk for FASD was increased in patients with increased ACE scores (RR = 5.08), increased numbers of neurodevelopmental diagnoses (RR = 2.36), and patients who have been in foster or residential care (RR = 9.53). FASD risk increased as ACE scores or the number of neurodevelopmental diagnoses increased. Patients with any ACEs were 3.96 times more likely to have FASD, and those with eight or more ACEs were 6.31 times more likely to have FASD than those with no ACEs. Patients with three or more neurodevelopmental diagnoses were 6.55 times more likely to have FASD than those with two or fewer diagnoses. Nine or more diagnoses increased the risk for FASD ten-fold (RR = 10.91). Conversely, patients diagnosed with FASD were more likely to have at least three ACEs (RR = 3.71), at least five neurodevelopmental diagnoses (RR = 1.61), and high rates of previous foster or residential care placement (RR = 5.39). </span><b><span style="font-family:Verdana;">Conclusion:</span> </b><span style="font-family:Verdana;">This study demonstrates that all children being considered for placement in foster care or residential should be screened for FASD.</span></span>展开更多
Background: In recent decades, there has been a growing interest in the impact of insults during pregnancy on postnatal health and disease. It is known that changes in placental development can impact fetal growth and...Background: In recent decades, there has been a growing interest in the impact of insults during pregnancy on postnatal health and disease. It is known that changes in placental development can impact fetal growth and subsequent susceptibility to adult onset diseases;however, a method to collect sufficient placental tissues for both histological and gene expression analyses during gestation without compromising the pregnancy has not been described. The ewe is an established biomedical model for the study of fetal development. Due to its cotyledonary placental type, the sheep has potential for surgical removal of materno-fetal exchange tissues, i.e., placentomes. A novel surgical procedure was developed in well-fed control ewes to excise a single placentome at mid-gestation.Results: A follow-up study was performed in a cohort of nutrient-restricted ewes to investigate rapid placental changes in response to undernutrition. The surgery averaged 19 min, and there were no viability differences between control and sham ewes. Nutrient restricted fetuses were smaller than controls(4.7 ± 0.1 kg vs. 5.6 ± 0.2 kg;P < 0.05), with greater dam weight loss(-32.4 ± 1.3 kg vs. 14.2 ± 2.2 kg;P < 0.01), and smaller placentomes at necropsy(5.7 ± 0.3 g vs. 7.2 ± 0.9 g;P < 0.05). Weight of sampled placentomes and placentome numbers did not differ.Conclusions: With this technique, gestational studies in the sheep model will provide insight into the onset and complexity of changes in gene expression in placentomes resulting from undernutrition(as described in our study),overnutrition, alcohol or substance abuse, and environmental or disease factors of relevance and concern regarding the reproductive health and developmental origins of health and disease in humans and in animals.展开更多
To investigate the effect of placental isoferritin （PLF） on mouse embryo development in vitro, mice 2-cell embryos were co-cultured with human first trimester decidual cells at different concentrations of PLF in vit...To investigate the effect of placental isoferritin （PLF） on mouse embryo development in vitro, mice 2-cell embryos were co-cultured with human first trimester decidual cells at different concentrations of PLF in vitro. The following changes of the above system were observed under an invert microscope and the number of embryos were recorded and the embryos were classified. The results showed there was no significant difference in the percentage of embryos development to 4-cell 8-cell and morula （P〉0.05）. PLF at the doses of 10 and 100 U/mL significantly enhanced more embryos development to the blastocyst and hatching blastocyst （P〈0.05）. PLF at the dose of 1000 U/mL depressed more embryos development from 2-cell to hatching blastocyst, meanwhile such phenomena as cell degeneration and irregular cleavage were observed in part of embryos, but there was no significant difference in statistics （P〉0.05）. It was concluded that PLF at the concentration of 10-- 100 U/mL had no significant effects on the early development of mice embryos, however, PLF could promote the growth, differentiation, and hatching of preimplantion blastocysts.展开更多
There is consistent epidemiological evidence linking low birth weight, preterm birth and adverse fetal growth to an elevated risk of the metabolic syndrome (obesity, raised blood pressure, raised serum triglycerides, ...There is consistent epidemiological evidence linking low birth weight, preterm birth and adverse fetal growth to an elevated risk of the metabolic syndrome (obesity, raised blood pressure, raised serum triglycerides, lowered serum high-density lipoprotein cholesterol and impaired glucose tolerance or insulin resistance) and related disorders. This "fetal or developmental origins/programming of disease" concept is now well accepted but the "programming" mechanisms remain poorly understood. We reviewed the major evidence, implications and limitations of current hypotheses in interpreting developmental programming and discuss future research directions. Major current hypotheses to interpret developmental programming include: (1)thrifty phenotype; (2) postnatal accelerated or catchup growth; (3) glucocorticoid effects; (4) epigenetic changes; (5) oxidative stress; (6) prenatal hypoxia; (7) placental dysfunction; and (8) reduced stem cell number. Some hypothetical mechanisms (2, 4 and 8) could be driven by other upstream "driver" mechanisms. There is a lack of animal studies addressing multiple mechanisms simultaneously and a lack of strong evidence linking clinical outcomes to biomarkers of the proposed programming mechanisms in humans. There are needs for (1) experimental studies addressing multiple hypothetical mechanisms simultaneously; and (2) prospective pregnancy cohort studies linking biomarkers of the proposed mechanisms to clinical outcomes or surrogate biomarker endpoints. A better understanding of the programming mechanisms is a prerequisite for developing early life interventions to arrest the increasing epidemic of the metabolic syndrome, type 2 diabetes and other related disorders.展开更多
Purpose: To investigate the relationship between preterm delivery and developmental outcomes in children born at 34 - 36 weeks of gestation (late preterm period). Methods: This study reviewed the cases of singleton la...Purpose: To investigate the relationship between preterm delivery and developmental outcomes in children born at 34 - 36 weeks of gestation (late preterm period). Methods: This study reviewed the cases of singleton late preterm children and full-term (38 - 40 weeks of gestation) children born at Showa University Hospital. The developmental outcomes at 3 years of age were assessed based on the results of questionnaires sent to the families by mail. In addition, the incidence of developmental delays was compared between the late preterm and full-term children. In the full-term control group, perinatal characteristics (neonatal gender, Apgar score, Cesarean delivery, birth weight < 10th percentile, birth weight < 3rd percentile) were matched with those of the late preterm cases. We compared categorical variables using Fisher’s exact test. For variables with a non-normal distribution, Welch’s t-test was applied. A p-value of <0.05 was considered to be statistically significant. Results: The rate of return of the questionnaires was 25.9% (121) among the cases and 25.8% (163) among the controls. The frequency of developmental delays was 6.6% among the cases, compared with 4.3% among the controls. Conclusions: Matching the perinatal characteristics of the subjects, the frequency of developmental delays was similar between the two groups.展开更多
Nonalcoholic fatty liver disease(NAFLD)has emerged as the prevailing chronic liver disease in the pediatric population due to the global obesity pandemic.Evidence shows that prenatal and postnatal exposure to maternal...Nonalcoholic fatty liver disease(NAFLD)has emerged as the prevailing chronic liver disease in the pediatric population due to the global obesity pandemic.Evidence shows that prenatal and postnatal exposure to maternal abnormalities leads to a higher risk of pediatric NAFLD through persistent alterations in developmental programming.Gestational diabetes mellitus(GDM)is a hyperglycemic syndrome which has become the most prevalent complication in pregnant women.An increasing number of both epidemiologic investigations and animal model studies have validated adverse and long-term outcomes in offspring following GDM exposure in utero.Similarly,GDM is considered a crucial risk factor for pediatric NAFLD.This review aimed to summarize currently published studies concerning the inductive roles of GDM in offspring NAFLD de velopment during childhood and adolescence.Dysregulations in hepatic lipid metabolism and gut microbiota in offspring,as well as dysfunctions in the placenta are potential factors in the pathogenesis of GDM-associated pediatric NAFLD.In addition,potentially effective interventions for GDM-associated offspring NAFLD are also discussed in this review.However,most of these therapeutic approaches still require further clinical research for validation.展开更多
目的评价新橙皮苷对大鼠胚胎-胎仔发育的毒性。方法妊娠大鼠根据妊娠第0天(gestation day 0,GD0)和体质量采用分层随机法分成5组:对照(0.5%羧甲基纤维素钠)组,环磷酰胺(12 mg·kg^(-1))组,新橙皮苷低、中、高(0.45,0.9,1.8g·kg...目的评价新橙皮苷对大鼠胚胎-胎仔发育的毒性。方法妊娠大鼠根据妊娠第0天(gestation day 0,GD0)和体质量采用分层随机法分成5组:对照(0.5%羧甲基纤维素钠)组,环磷酰胺(12 mg·kg^(-1))组,新橙皮苷低、中、高(0.45,0.9,1.8g·kg^(-1))3个剂量组。妊娠鼠于GD6开始给药至GD15。实验期间,每周至少测定2次体质量和1次摄食量。GD20处死妊娠鼠,对黄体、着床腺、胎仔、胎盘等情况进行检查。结果试验期间,各组动物临床症状观察均未见明显异常。与对照组相比,新橙皮苷各剂量组动物体质量未见明显改变,环磷酰胺组动物增重减缓;新橙皮苷各剂量组黄体、着床、活胎、吸收胎、死胎计数均未见明显改变,环磷酰胺组子宫重量下降;新橙皮苷高剂量组胎仔身长降低,环磷酰胺组身长、尾长、重量及胎盘重均降低;新橙皮苷各剂量组胎仔外观检查未见给药相关改变,环磷酰胺组主要可见全身浮肿、头、耳、面、肢、指趾等改变。胎仔内脏检查中,新橙皮苷各剂量组分别可见1例脑室改变,中、高剂量组分别可见2例和1例食管扩张;环磷酰胺组可见腭、脑室、食管、睾丸附睾等改变。骨骼检查中,新橙皮苷可延缓顶骨、胸骨的骨化,可能影响下颌骨、颈椎、腰椎、耻骨、枕骨和肋骨的骨化。环磷酰胺12mg·kg^(-1)对颅骨、脊椎骨、肋骨、胸骨、掌骨等的骨化均有所影响。结论新橙皮苷给药后,对母体未产生明显毒性反应,未观察到临床不良反应的剂量水平(NOAEL)为1.8 g·kg^(-1);对胚胎-胎仔的发育毒性主要表现为延缓骨骼如顶骨、胸骨等的骨化外,还可能影响脑部和食管的发育,NOAEL<0.45 g·kg^(-1)。展开更多
目的评价活血消异方对子宫内膜异位症模型大鼠胎仔—围产期发育毒性的影响。方法采用改良同种异体移植法建立子宫内膜异位症模型大鼠,设空白组、模型组及假手术组,并以低剂量(每毫升1.8 g 生药)、高剂量(每毫升3.6 g 生药)的活血消异方...目的评价活血消异方对子宫内膜异位症模型大鼠胎仔—围产期发育毒性的影响。方法采用改良同种异体移植法建立子宫内膜异位症模型大鼠,设空白组、模型组及假手术组,并以低剂量(每毫升1.8 g 生药)、高剂量(每毫升3.6 g 生药)的活血消异方灌胃,妊娠第20天处死部分大鼠,观察各组胎鼠数量、体质量、身长、尾长以及畸形情况;另有部分孕鼠自然分娩后比较各组子代断乳后存活率、畸形率及离乳后子代体质量、成年后生育力等。结果孕20 d模型组大鼠平均胎鼠数量明显少于其他各组(P<0.05);活血消异方高、低剂量组平均胎鼠数明显高于模型组(P<0.05);模型组胎鼠体质量、身长、尾长与空白组、假手术组比较,差异无统计学意义(P>0.05);中药组胎鼠体质量、身长、尾长略低于空白组及模型组(P<0.05);各组胎仔骨骼均未出现缺失和畸形。离乳前各组子代大鼠体格发育正常,断乳后子代畸形率、死亡率、存活率之间无明显差异(P>0.05);中药低、高剂量组子代断乳后体质量高于空白组、假手术组、模型组(P<0.05)。结论子宫内膜异位症疾病本身对大鼠妊娠能力有一定影响,但对大鼠胎仔及围产期发育无明显毒性;活血消异方组胎鼠体质量、身长、尾长略低于空白组及模型组,可能与胎鼠数量较多有关;且中药高、低剂量组胎鼠均无外观畸形及骨骼畸形,离乳时体格发育正常,子代大鼠断乳后无明显体质量偏低,提示活血消异方对大鼠胎仔及围产期发育并无明显毒性,但仍需进一步实验验证。展开更多
大量流行病学和动物实验研究显示,发育早期不利因素,特别是宫内营养失衡(包括营养不良及营养过剩),导致机体生理和代谢发生永久改变,引发子代肥胖、2型糖尿病、高血压、冠心病等成年慢性疾病的发生发展。这一过程发生在胎儿发育的窗口期...大量流行病学和动物实验研究显示,发育早期不利因素,特别是宫内营养失衡(包括营养不良及营养过剩),导致机体生理和代谢发生永久改变,引发子代肥胖、2型糖尿病、高血压、冠心病等成年慢性疾病的发生发展。这一过程发生在胎儿发育的窗口期,即健康和疾病的发育起源(developmental origins of health and disease,DOHaD)。目前,其具体机制引发了国内外学者的广泛关注,特别是代谢调节关键基因在转录水平的改变及表观遗传学在引发成年代谢表型中的作用。深入了解并进一步探讨其机制以寻求有效的干预方式对控制心血管疾病及2型糖尿病的流行意义重大,对于经济快速转型的发展中国家更是意义深远。展开更多
基金funded by the following Grants:National Natural Science Foundation of China,Grant/Award Number:81370724,81571463 and 81401225Innovative Research Program for Postgraduate in Higher Education Institutions of Jiangsu Province for the year 2016,Grant/Award Number:KYLX16_1111
文摘Preeclampsia is associated with over-activation of the innate immune system in the placenta,in which toll-like receptor 4（TLR4） plays an essential part.With their potent anti-inflammatory effects,statins have been suggested as potential prevention or treatment of preeclampsia,although evidence remains inadequate.Herewith,we investigated whether pravastatin could ameliorate preeclampsia-like phenotypes in a previously established lipopolysaccharide（LPS）-induced rat preeclampsia model,through targeting the TLR4/NF-κB pathway.The results showed that pravastatin reduced the blood pressure [maximum decline on gestational day（GD） 12,（101.33±2.49） mmHg vs.（118.3±1.37） mmHg,P〈0.05] and urine protein level [maximum decline on GD9,（3,726.23± 1,572.86） μg vs.（1,991.03 ±609.37）μg,P〈 0.05],which were elevated following LPS administration.Pravastatin also significantly reduced the rate of fetal growth restriction in LPS-treated rats（34.10% vs.8.99%,P〈0.05）.Further pathological analyses suggested a restoration of normal spiral artery remodeling in preeclampsia rats by pravastatin treatment.These effects of pravastatin were associated with decreased TLR4/NF-κB protein levels in the placenta and IL-6/MCP-1 levels in serum.Additionally,no obvious abnormalities in fetal liver,brain,and kidney were found after administration of pravastatin.These results provide supportive evidence for use of pravastatin in preventing preeclampsia.
基金supported by the National Key Research and Development Program of China (No.2020YFA0803900)。
文摘Amoxicillin,a widely used antibiotic in human and veterinary pharmaceuticals,is now considered as an“emerging contaminant”because it exists widespreadly in the environment and brings a series of adverse outcomes.Currently,systematic studies about the developmental toxicity of amoxicillin are still lacking.We explored the potential effects of amoxicillin exposure on pregnancy outcomes,maternal/fetal serum phenotypes,and fetal multiple organ development in mice,at different doses(75,150,300 mg/(kg·day))during late-pregnancy,or at a dose of 300 mg/(kg·day)during different stages(mid-/latepregnancy)and courses(single-/multi-course).Results showed that prenatal amoxicillin exposure(PAmE)had no significant infuence on the body weights of dams,but it could inhibit the physical development and reduce the survival rate of fetuses,especially during the midpregnancy.Meanwhile,PAmE altered multiple maternal/fetal serum phenotypes,especially in fetuses.Fetal multi-organ function results showed that PAmE inhibited testicular/adrenal steroid synthesis,long bone/cartilage and hippocampal development,and enhanced ovarian steroid synthesis and hepatic glycogenesis/lipogenesis,and the order of severity might be gonad(testis,ovary)>liver>others.Further analysis found that PAmE-induced multiorgan developmental and functional alterations had differences in stages,courses and fetal gender,and the most obvious changes might be in high-dose,late-pregnancy and multicourse,but there was no typical rule of a dose-response relationship.In conclusion,this study confirmed that PAmE could cause abnormal development and multi-organ function alterations,which deepens our understanding of the risk of PAmE and provides an experimental basis for further exploration of the long-term harm.
基金supported by the National Natural Science Foundation of China[81701350 and 31671252]the Health Technology Plan of Zhejiang Province[2023RC205].
文摘Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders(NDDs)in the offspring,especially in the case of drug exposure.However,little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors.We collected and manually curated sub-pathways and pathways(sub-/pathways)and drug information to propose an analytical framework for predicting drug candidates.This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs.Further,specific and pleiotropic sub-/pathways/drugs were identified using entropy,and sex bias was analyzed in conjunction with logistic regression and random forest models.We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs,showing temporal or spatial changes across fetal development.Moreover,5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels.A user-friendly NDDP visualization website(https://ndd-lab.shinyapps.io/NDDP)was developed to allow researchers and clinicians to access and retrieve data easily.Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories.This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.
文摘<strong>Objectiv</strong><strong>e</strong><strong>:</strong><span style="font-family:""><span style="font-family:Verdana;"> Children with fetal alcohol spectrum disorder (FASD) are overrepresented in early intervention programs, foster care, special education, juvenile corrections, and mental health services. In this study, we examine relationships between FASD and non-FASD controls for adverse childhood experiences (ACEs), and neurodevelopmental disorders. </span><b><span style="font-family:Verdana;">Methods:</span> </b><span style="font-family:Verdana;">A chart review was conducted among patients seen at our clinic from 2010-2017 with data on FASD, ACEs, neurodevelopmental diagnoses, and foster or residential care placement available. </span><b><span style="font-family:Verdana;">Results:</span> </b><span style="font-family:Verdana;">Relative risk for FASD was increased in patients with increased ACE scores (RR = 5.08), increased numbers of neurodevelopmental diagnoses (RR = 2.36), and patients who have been in foster or residential care (RR = 9.53). FASD risk increased as ACE scores or the number of neurodevelopmental diagnoses increased. Patients with any ACEs were 3.96 times more likely to have FASD, and those with eight or more ACEs were 6.31 times more likely to have FASD than those with no ACEs. Patients with three or more neurodevelopmental diagnoses were 6.55 times more likely to have FASD than those with two or fewer diagnoses. Nine or more diagnoses increased the risk for FASD ten-fold (RR = 10.91). Conversely, patients diagnosed with FASD were more likely to have at least three ACEs (RR = 3.71), at least five neurodevelopmental diagnoses (RR = 1.61), and high rates of previous foster or residential care placement (RR = 5.39). </span><b><span style="font-family:Verdana;">Conclusion:</span> </b><span style="font-family:Verdana;">This study demonstrates that all children being considered for placement in foster care or residential should be screened for FASD.</span></span>
文摘Background: In recent decades, there has been a growing interest in the impact of insults during pregnancy on postnatal health and disease. It is known that changes in placental development can impact fetal growth and subsequent susceptibility to adult onset diseases;however, a method to collect sufficient placental tissues for both histological and gene expression analyses during gestation without compromising the pregnancy has not been described. The ewe is an established biomedical model for the study of fetal development. Due to its cotyledonary placental type, the sheep has potential for surgical removal of materno-fetal exchange tissues, i.e., placentomes. A novel surgical procedure was developed in well-fed control ewes to excise a single placentome at mid-gestation.Results: A follow-up study was performed in a cohort of nutrient-restricted ewes to investigate rapid placental changes in response to undernutrition. The surgery averaged 19 min, and there were no viability differences between control and sham ewes. Nutrient restricted fetuses were smaller than controls(4.7 ± 0.1 kg vs. 5.6 ± 0.2 kg;P < 0.05), with greater dam weight loss(-32.4 ± 1.3 kg vs. 14.2 ± 2.2 kg;P < 0.01), and smaller placentomes at necropsy(5.7 ± 0.3 g vs. 7.2 ± 0.9 g;P < 0.05). Weight of sampled placentomes and placentome numbers did not differ.Conclusions: With this technique, gestational studies in the sheep model will provide insight into the onset and complexity of changes in gene expression in placentomes resulting from undernutrition(as described in our study),overnutrition, alcohol or substance abuse, and environmental or disease factors of relevance and concern regarding the reproductive health and developmental origins of health and disease in humans and in animals.
文摘To investigate the effect of placental isoferritin （PLF） on mouse embryo development in vitro, mice 2-cell embryos were co-cultured with human first trimester decidual cells at different concentrations of PLF in vitro. The following changes of the above system were observed under an invert microscope and the number of embryos were recorded and the embryos were classified. The results showed there was no significant difference in the percentage of embryos development to 4-cell 8-cell and morula （P〉0.05）. PLF at the doses of 10 and 100 U/mL significantly enhanced more embryos development to the blastocyst and hatching blastocyst （P〈0.05）. PLF at the dose of 1000 U/mL depressed more embryos development from 2-cell to hatching blastocyst, meanwhile such phenomena as cell degeneration and irregular cleavage were observed in part of embryos, but there was no significant difference in statistics （P〉0.05）. It was concluded that PLF at the concentration of 10-- 100 U/mL had no significant effects on the early development of mice embryos, however, PLF could promote the growth, differentiation, and hatching of preimplantion blastocysts.
基金Supported by a Research Grant from the Canadian Institutes of Health Research (CIHR), Institute of Nutrition, Metabolism and Diabetes (CIHR Grant # 79896 - Luo ZC)partly by a Clinical Epidemiology Junior Scholar Award from the Fonds de la Recherche en Santé du Québec (FRSQ) (Luo ZC)partly by a FRSQ Senior Scholar Award (Nuyt AM)
文摘There is consistent epidemiological evidence linking low birth weight, preterm birth and adverse fetal growth to an elevated risk of the metabolic syndrome (obesity, raised blood pressure, raised serum triglycerides, lowered serum high-density lipoprotein cholesterol and impaired glucose tolerance or insulin resistance) and related disorders. This "fetal or developmental origins/programming of disease" concept is now well accepted but the "programming" mechanisms remain poorly understood. We reviewed the major evidence, implications and limitations of current hypotheses in interpreting developmental programming and discuss future research directions. Major current hypotheses to interpret developmental programming include: (1)thrifty phenotype; (2) postnatal accelerated or catchup growth; (3) glucocorticoid effects; (4) epigenetic changes; (5) oxidative stress; (6) prenatal hypoxia; (7) placental dysfunction; and (8) reduced stem cell number. Some hypothetical mechanisms (2, 4 and 8) could be driven by other upstream "driver" mechanisms. There is a lack of animal studies addressing multiple mechanisms simultaneously and a lack of strong evidence linking clinical outcomes to biomarkers of the proposed programming mechanisms in humans. There are needs for (1) experimental studies addressing multiple hypothetical mechanisms simultaneously; and (2) prospective pregnancy cohort studies linking biomarkers of the proposed mechanisms to clinical outcomes or surrogate biomarker endpoints. A better understanding of the programming mechanisms is a prerequisite for developing early life interventions to arrest the increasing epidemic of the metabolic syndrome, type 2 diabetes and other related disorders.
文摘Purpose: To investigate the relationship between preterm delivery and developmental outcomes in children born at 34 - 36 weeks of gestation (late preterm period). Methods: This study reviewed the cases of singleton late preterm children and full-term (38 - 40 weeks of gestation) children born at Showa University Hospital. The developmental outcomes at 3 years of age were assessed based on the results of questionnaires sent to the families by mail. In addition, the incidence of developmental delays was compared between the late preterm and full-term children. In the full-term control group, perinatal characteristics (neonatal gender, Apgar score, Cesarean delivery, birth weight < 10th percentile, birth weight < 3rd percentile) were matched with those of the late preterm cases. We compared categorical variables using Fisher’s exact test. For variables with a non-normal distribution, Welch’s t-test was applied. A p-value of <0.05 was considered to be statistically significant. Results: The rate of return of the questionnaires was 25.9% (121) among the cases and 25.8% (163) among the controls. The frequency of developmental delays was 6.6% among the cases, compared with 4.3% among the controls. Conclusions: Matching the perinatal characteristics of the subjects, the frequency of developmental delays was similar between the two groups.
基金supported by grants from the National Nat-ural Science Foundation of China(82170593)National Key R&D Program of China(2021YFC2700802)Collaborative Innovation Program of Shanghai Municipal Health Commission(2020CXJQ01)。
文摘Nonalcoholic fatty liver disease(NAFLD)has emerged as the prevailing chronic liver disease in the pediatric population due to the global obesity pandemic.Evidence shows that prenatal and postnatal exposure to maternal abnormalities leads to a higher risk of pediatric NAFLD through persistent alterations in developmental programming.Gestational diabetes mellitus(GDM)is a hyperglycemic syndrome which has become the most prevalent complication in pregnant women.An increasing number of both epidemiologic investigations and animal model studies have validated adverse and long-term outcomes in offspring following GDM exposure in utero.Similarly,GDM is considered a crucial risk factor for pediatric NAFLD.This review aimed to summarize currently published studies concerning the inductive roles of GDM in offspring NAFLD de velopment during childhood and adolescence.Dysregulations in hepatic lipid metabolism and gut microbiota in offspring,as well as dysfunctions in the placenta are potential factors in the pathogenesis of GDM-associated pediatric NAFLD.In addition,potentially effective interventions for GDM-associated offspring NAFLD are also discussed in this review.However,most of these therapeutic approaches still require further clinical research for validation.
文摘目的评价活血消异方对子宫内膜异位症模型大鼠胎仔—围产期发育毒性的影响。方法采用改良同种异体移植法建立子宫内膜异位症模型大鼠,设空白组、模型组及假手术组,并以低剂量(每毫升1.8 g 生药)、高剂量(每毫升3.6 g 生药)的活血消异方灌胃,妊娠第20天处死部分大鼠,观察各组胎鼠数量、体质量、身长、尾长以及畸形情况;另有部分孕鼠自然分娩后比较各组子代断乳后存活率、畸形率及离乳后子代体质量、成年后生育力等。结果孕20 d模型组大鼠平均胎鼠数量明显少于其他各组(P<0.05);活血消异方高、低剂量组平均胎鼠数明显高于模型组(P<0.05);模型组胎鼠体质量、身长、尾长与空白组、假手术组比较,差异无统计学意义(P>0.05);中药组胎鼠体质量、身长、尾长略低于空白组及模型组(P<0.05);各组胎仔骨骼均未出现缺失和畸形。离乳前各组子代大鼠体格发育正常,断乳后子代畸形率、死亡率、存活率之间无明显差异(P>0.05);中药低、高剂量组子代断乳后体质量高于空白组、假手术组、模型组(P<0.05)。结论子宫内膜异位症疾病本身对大鼠妊娠能力有一定影响,但对大鼠胎仔及围产期发育无明显毒性;活血消异方组胎鼠体质量、身长、尾长略低于空白组及模型组,可能与胎鼠数量较多有关;且中药高、低剂量组胎鼠均无外观畸形及骨骼畸形,离乳时体格发育正常,子代大鼠断乳后无明显体质量偏低,提示活血消异方对大鼠胎仔及围产期发育并无明显毒性,但仍需进一步实验验证。
文摘大量流行病学和动物实验研究显示,发育早期不利因素,特别是宫内营养失衡(包括营养不良及营养过剩),导致机体生理和代谢发生永久改变,引发子代肥胖、2型糖尿病、高血压、冠心病等成年慢性疾病的发生发展。这一过程发生在胎儿发育的窗口期,即健康和疾病的发育起源(developmental origins of health and disease,DOHaD)。目前,其具体机制引发了国内外学者的广泛关注,特别是代谢调节关键基因在转录水平的改变及表观遗传学在引发成年代谢表型中的作用。深入了解并进一步探讨其机制以寻求有效的干预方式对控制心血管疾病及2型糖尿病的流行意义重大,对于经济快速转型的发展中国家更是意义深远。
