REPRODUCTIVE TOXICOLOGY
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2016
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IF 2.85
Hua Wang,Ying Wang,Qing-Li Bo,Yan-Li Ji,Lu Liu,Yong-Fang Hu,Yuan-Hua Chen,Jun Zhang,Ling-Li Zhao,De-Xiang Xu
Cadmium (Cd) is linked with increased risk of fetal growth restriction (FGR). Nevertheless, the mechanism remains unknown. This study established a mouse model of Cd-induced FGR through two exposure methods. Pregnant mice were either administered with CdCl 2 (5, 50 and 250 ppm) throughout pregnancy through drinking water or intraperitoneally injected with CdCl 2 (4.5 mg/kg) on GD9. As expected, fetal weight and crown-rump length were reduced in a gender-independent manner. Interestingly, Mt1 and Mt2, two metallothionein genes, were up-regulated in maternal liver. Correspondingly, Cd accumulated mainly in maternal liver and kidney, and only trace amounts of Cd could pass from dam to placentas and fetuses. Further analysis showed that placental Zn concentration was elevated. Conversely, embryonic Zn concentration was reduced. Moreover, placental Znt1 and Znt2 , two zinc transporters, were down-regulated in Cd-exposed mice. These results suggest that maternal Cd exposure during pregnancy reduces placental Zn transport and induces fetal growth restriction.
研究领域:
毒理学
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生殖生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2021
·
IF 6.057
Yanan Song,Jingyi Sun,Chunmei Li,Li Lin,Feng Gao,Mingfeng Yang,Baoliang Sun,Ying Wang
Sensitive and accurate early detection of fetal growth restriction (FGR) is of vital importance in the development of the fetus during pregnancy and even the health of future life. Here, an ultrasensitive and straightforward surface-enhanced Raman scattering (SERS)-based double targets detection in pregnancy is implemented by utilizing functionalized Ag nanoparticles (AgNPs). Through fabricating 4-MPA antibody-modified AgNPs on the lateral flow assay (LFA) strips as the SERS nanotags, the target proteins in blood samples from pregnancy were accurately captured, which further quantizing PI3K and CRAF in unprocessed blood. This strategy warrant excellent selectivity and sensitivity with the limits of detection (LODs) are 0.76 fg mL −1 for PI3K and 0.61 fg mL −1 for CRAF, leading reliable quantification for these two targets. Meanwhile, the feasibility of this assembly was testified by comparing with conventional ELISA method, and the results showed that a high degree of consistency was obtained in these two detection assays. This SERS-colorimetric dual-signal LFA strip can provide a novel strategy for early diagnosis of fetal-related disorders, which is essential for disease diagnosis and treatment guidance during pregnancy.
研究领域:
医学诊断
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纳米技术
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孕期健康
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产品关联
DOI
PubMed
高影响因子
ISME Journal
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2025
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IF 10
Wei Yusen,Mao Jiangdi,Tang Wenjie,Ma Yanfei,Li Jiachen,Su Songtao,Ni Zhixiang,Wu Jinhong,Liu Daren,Wang Haifeng
Male offspring with intrauterine growth restriction exhibit more pronounced hepatic lipid metabolism abnormalities than females, necessitating earlier intervention. Icariin has been shown to effectively modulate hepatic lipid metabolism in male piglets with intrauterine growth restriction. However, the role of gut microbiota in this process remains to be elucidated. This study aimed to explore the influence of gut microbiota on icariin-induced enhancement of hepatic lipid metabolism. By examining changes in microbiota composition and hepatic lipid metabolism following icariin intervention, the study demonstrated an association between microbial alterations and hepatic lipid regulation through fecal microbiota transplantation. The impact of Catenibacterium on gut microbiota structure and hepatic lipid metabolism was assessed in vivo, and the direct effect of icariin on Catenibacterium was explored in vitro. Results revealed that icariin intervention modified fecal, ileal, and colonic microbiota in male piglets with intrauterine growth restriction, enhanced gut morphology and barrier function, and normalized the expression of hepatic peroxisome proliferator-activated receptor (PPAR) signaling pathway-related genes. Fecal microbiota transplantation from piglets with intrauterine growth restriction impaired intestinal barrier function and led to hepatic lipid deposition, whereas transplantation from icariin-treated donors showed no pathological changes, an outcome associated with reduced abundance of Catenibacterium. Mechanistically, icariin inhibits adenosine triphosphate synthesis to suppress Catenibacterium, remodels gut microbiota, reduces lipopolysaccharide production and translocation, and activates the hepatic PPARα/CD36 axis. In conclusion, icariin intervention alleviates hepatic lipid metabolic disorders in male offspring with intrauterine growth restriction by suppressing Catenibacterium, restoring gut microbial balance, and enhancing intestinal barrier integrity to limit lipopolysaccharide translocation.
研究领域:
微生物学
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药理学
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营养学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ENVIRONMENTAL MANAGEMENT
·
2025
·
IF 8.4
Lumei Xie,Hongli Liu,Xinyue Hu,Jiacheng Xu,Bingdi Chao,Jie Wang,Lujia Sun,Xiyao Liu,Niya Zhou,Luming Sun,Hongbo Qi,Xin Luo
Decabromodiphenyl ethane (DBDPE), a newly emerging brominated flame retardant (BFR), has garnered increasing attention due to its high production volumes and widespread usage, prompting worries about its possible impacts on human well-being. Prior investigations have highlighted the substantial toxicity of DBDPE to the thyroid, liver, and cardiovascular systems, yet its effects on fetal growth and development remain inadequately understood. This investigation aims to elucidate the underlying mechanisms and consequences of DBDPE exposure on fetal growth and development through both in vivo and in vitro models. Pregnant mice were administered DBDPE orally at doses of 0, 0.05, 0.5, and 5 mg/kg bw/day. Results revealed that gestational DBDPE exposure caused placental damage, resulting in fetal growth restriction (FGR). A significant reduction in the phosphorylation level of AIFM1 Ser116 in placental trophoblasts was observed, specifically correlating with the activation of oxeiptosis. Metabolomic and transcriptomic analyses further suggested that DBDPE exposure disrupts the oxidative phosphorylation (OXPHOS) pathway, thereby impairing mitochondrial function. Notably, treatment with MitoQ, a mitochondria-targeted antioxidant, effectively reversed DBDPE-induced oxeiptosis in placental trophoblasts, alleviating the negative effects of DBDPE on placental damage and FGR. Mechanistically, the mitochondrial dysfunction induced by gestational DBDPE exposure initiates oxeiptosis in placental trophoblasts, exacerbating placental injury and ultimately leading to FGR. In summary, this study integrates the roles of environmental pollutants, oxeiptosis, and mitochondrial dysfunction, offering new insights into the toxicological mechanisms by which DBDPE and other emerging pollutants impact fetal growth and development.
研究领域:
环境毒理学
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生殖生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2025
·Vol. 39
·期 11
·e70691
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IF 4.2
Jianfeng Dong,Wen Chen,Shujuan Chang,Nana Liu,Wei Zhu,Li Ma,Jing Qiao,Yuhang Wang,Zhiyong Mao,Jiuhong Kang
Infants born with fetal growth restriction (FGR) are at increased risk of cognitive impairment in later life, yet the underlying mechanisms remain poorly understood, hampering clinical treatment development. Utilizing a FGR mouse model induced by prenatal dexamethasone overexposure, we observed impaired hippocampal dendritic maturation, synaptic plasticity, and hippocampal‐dependent learning and memory in FGR mice. FGR induces DNA hypomethylation in the hippocampal H19/Igf2 imprinted control region, resulting in reduced expression of Igf2, a key metabolic modulator previously implicated in FGR‐related placental and fetal growth. Using a neuron‐specific knockout mouse model, we validated the necessity of Igf2 for dendritic maturation and synaptic plasticity. Importantly, overexpression of Igf2 in the hippocampus of FGR mice improved synaptic plasticity and enhanced learning and memory abilities. Furthermore, running exercise ameliorated DNA hypomethylation driving Igf2 expression levels and counteracted synaptic and cognitive deficits in FGR mice through hippocampal Igf2. These findings unveil a molecular mechanism linking exercise‐induced epigenetic changes in the imprinting gene Igf2 to enhanced synaptic plasticity, ultimately leading to improved cognition in FGR offspring. Our results identify Igf2 as a potential mediator bridging metabolic dysfunction and cognitive impairments in FGR offspring and also propose that exercise represents a promising nondrug intervention for FGR‐related cognitive disorders. Fetal growth restriction (FGR) induces hippocampal DNA hypomethylation and loss of Igf2, contributing to impaired synaptic plasticity and cognitive deficits in offspring. Exercise restores Igf2 levels and rescues these impairments, suggesting a potential therapeutic strategy for FGR‐related cognitive dysfunction.
研究领域:
神经科学
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分子生物学
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医学
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DOI
PubMed
高影响因子
Reproductive Sciences
·
2023
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IF 2.9
Dai Yan,Sang Xiu-Bo,Bai Wen-Pei
Fetal growth restriction (FGR) seriously threatens perinatal health. The main cause of FGR is placental malperfusion, but the specific mechanism is still unclear, and there is no effective treatment for FGR. We constructed a FGR mouse model by adding exogenous asymmetric dimethylarginine (ADMA) through in vivo experiments and found that ADMA could cause placental dysplasia and induce the occurrence of FGR. Compared with the control group, reactive oxygen species (ROS) production in the placenta was increased in mice with FGR, and the expression of autophagy-related proteins p-AKT/AKT, p-mTOR/mTOR, and P62 was significantly decreased, while the expression of Beclin-1 and LC3-II was significantly increased in the FGR group. Furthermore, ADMA had a favorable effect in promoting the formation of autophagosomes. Hydroxychloroquine (HCQ) and N-acetylcysteine (NAC) improved ADMA-induced disorders of placental development and alleviated ADMA-induced FGR. This study found that ADMA could cause excessive autophagy of trophoblasts by increasing the level of oxidative stress, ultimately leading to the occurrence of FGR, and HCQ and NAC had therapeutic effects on ADMA-induced FGR.
研究领域:
药理学
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妇产科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of the American Heart Association
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2022
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IF 6.106
Xiaofei Luo,Chengcheng Hang,Ziming Zhang,Kaixing Le,Yuhan Ying,Ying Lv,Lingling Yan,Yajie Huang,Lixia Ye,Xuefeng Xu,Ying Zhong,Lizhong Du
BackgroundIntrauterine growth restriction (IUGR) is closely related to systemic or pulmonary hypertension (PH) in adulthood. Aberrant crosstalk between pulmonary vascular endothelial cells (PVECs) and pulmonary arterial smooth muscle cells (PASMCs) that is mediated by exosomes plays an essential role in the progression of PH. FoxM1 (Forkhead box M1) is a key transcription factor that governs many important biological processes.Methods and ResultsIUGR‐induced PH rat models were established. Transwell plates were used to coculture PVECs and PASMCs. Exosomes were isolated from PVEC‐derived medium, and a microRNA (miRNA) screening was proceeded to identify effects of IUGR on small RNAs enclosed within exosomes. Dual‐Luciferase assay was performed to validate the predicted binding sites of miRNAs on FoxM1 3’ untranslated region. FoxM1 inhibitor thiostrepton was used in IUGR‐induced PH rats. In this study, we found that FoxM1 expression was remarkably increased in IUGR‐induced PH, and PASMCs were regulated by PVECs through FoxM1 signaling in a non‐contact way. An miRNA screening showed that miR‐214‐3p, miR‐326‐3p, and miR‐125b‐2‐3p were downregulated in PVEC‐derived exosomes of the IUGR group, which were associated with overexpression of FoxM1 and more significant proliferation and migration of PASMCs. Dual‐Luciferase assay demonstrated that the 3 miRNAs directly targeted FoxM1 3’ untranslated region. FoxM1 inhibition blocked the PVECs‐PASMCs crosstalk and reversed the abnormal functions of PASMCs. In vivo, treatment with thiostrepton significantly reduced the severity of PH.ConclusionsTransmission of exosomal miRNAs from PVECs regulated the functions of PASMCs via FoxM1 signaling, and FoxM1 may serve as a potential therapeutic target in IUGR‐induced PH.
研究领域:
心血管疾病
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分子生物学
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细胞生物学
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转化医学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Siqi Zhang,Zedan Pu,Zhiyu Chen,E Gong,Hanwen Zhang,Qian Gui,Xuehai Chen,Juan Cheng,Hongbo Qi
Fetal growth restriction (FGR) is a common pregnancy complication linked to adverse perinatal outcomes, yet effective therapeutic options remain lacking due to insufficient mechanistic understanding. Through integrated analyses of human and rat models of FGR placenta, combined with in-depth placental cell investigation, it is identified that placental hypoxia triggers oxidative stress, cellular dysfunction, and pro-inflammatory cytokine activation, collectively contributing to FGR pathogenesis. Building on these findings, a nanotherapeutic platform (PPA NP) is engineered via a one-pot self-assembly approach. This formulation incorporates a reactive oxygen species (ROS)-scavenging unit (PBE), a clinical medication that may prevent FGR (aspirin), and polyethyleneimine (PEI), where PBE and aspirin cooperatively mediated the self-assembly of PEI. In vitro, PPA NP exerts multiple therapeutic activities, including anti-apoptotic activity, attenuation of oxidative stress, and enhancement of trophoblast invasion, migration, and endothelial tube formation. In the rat model, PPA NP effectively mitigates FGR by alleviating hypoxia, oxidative stress, vascular injury, and inflammation within the embryonic microenvironment. Critically, PPA NP displays no discernible toxicity to maternal or fetal tissues, even at doses exceeding the therapeutic range. Together, these results highlight PPA NP as a promising and safe nanotherapeutic strategy for FGR, with the potential to address the clinical need for effective interventions in pregnancy complications.
研究领域:
妇产科学
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发育生物学
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纳米医学
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分子病理学
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围产医学
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氧化还原生物学
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药理学
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转化医学
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产品关联
DOI
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2025
·
IF 11.3
Run Ling,Xin Yin,Liyao Ma,Yan Zhang,Yidan Ma,Rufei Gao,Yanqing Geng,Xinyi Mu,Xuemei Chen,Fangfang Li,Junlin He
Decabromodiphenyl ethane (DBDPE) is a brominated flame retardant widely used for its high flame retardancy and low bioavailability. However, DBDPE exhibits bioaccumulative potential. The placental vasculature, critical for the exchange between maternal and fetal circulation, is susceptible to environmental factors. We aimed to understand the potential toxicity of DBDPE to the placental vasculature. Gestational CD-1 mice and human umbilical vein endothelial cells (HUVECs) were exposed to 0, 0.5, 5, 50 mg/kg·bw·day or 0, 6.25, 12.5, 25, 50 μmol/L DBDPE, respectively. DBDPE exposure impaired placental angiogenesis and inhibited the proliferation and invasion of HUVECs by activating the endothelial-to-mesenchymal transition (EndMT) through the TGF-β1/Smad pathway, in vivo and in vitro . DBDPE upregulated the transcription factor TWIST2 and mRNA acetyltransferase NAT10. Knockdown or overexpression of TWIST2 reversed the vascular dysfunction and EndMT mechanism. DBDPE facilitated the recruitment of NAT10 by TWIST2, promoting N4-acetylcytidine (ac4C) RNA modifications and stabilizing the TGF-β1 mRNA. NAT10 inhibition rescued the effects caused by DBDPE. These findings uncover molecular mechanisms linking DBDPE exposure to adverse pregnancy outcomes, highlighting potential risks to pregnant women.
研究领域:
毒理学
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生殖生物学
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分子生物学
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环境健康
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细胞生物学
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RNA修饰
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发育生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Miao Tang,Yu Xin,Yunchun Zhao,Xiao Zhang,Meng Zhang,Dongli Sun,Xiaojun Zhu,Yao Yao,Weidong Fei,Caihong Zheng
Physiological or pathological hypoperfusion of the placenta is one of the main causes of intrauterine growth restriction (IUGR) which poses a significant risk to the health of the fetus and newborn. Tadalafil, a 5-type phosphodiesterase inhibitor, has previously been found to improve the symptoms of IUGR in various clinical studies. Unfortunately, its clinical utility is hindered by its limited water solubility, rapid metabolism, and lack of specific distribution in target tissues rendering tadalafil unable to maintain long-term placental perfusion. In this study, iRGD-modified tadalafil-loaded liposomes (iRGD-lipo@Tad) featuring a size of approximately 480 nm were designed to rectify the shortcomings of tadalafil. The prepared iRGD-lipo@Tad exhibited superior stability, sustained drug release capacity, and low cytotoxicity. The fluorescence study, tissue slice study, and drug biodistribution study together demonstrated the placenta-anchored ability of iRGD-modified liposomes. This was achieved by a dual approach consisting of the iRGD-mediated placenta-targeting effect and special particle size-mediated placenta resident effect. The pharmacokinetic study revealed a significant improvement in the in vivo process of tadalafil encapsulated by the iRGD-modified liposomes. In comparison to the tadalafil solution, the peak plasma concentration of iRGD-lipo@Tad was significantly increased, and the area under the curve was increased by about 7.88 times. In the pharmacodynamic study, iRGD-lipo@Tad achieved a continuous and efficient improvement of placental blood perfusion. This was achieved by decreasing the ratio of plasma soluble fms-like tyrosine kinase to placental growth factor and increasing the levels of cyclic guanosine monophosphate and nitric oxide. Consequently, iRGD-lipo@Tad resulted in a significant increase in embryo weight and a reduction in the miscarriage rate of N-Nitro-L-arginine methyl ester-induced IUGR pregnant mice without detectable toxicity. In summary, the nanotechnology-assisted therapy strategy presented here not only overcomes the limitations of tadalafil in the clinical treatment of IUGR but also offers new avenues to address the treatment of other placenta-originated diseases.
研究领域:
药理学
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妇产科学
·
纳米技术
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生物医学工程
·
生殖医学
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产品关联
DOI
PubMed
高影响因子
AQUATIC TOXICOLOGY
·
2023
·
IF 4.5
Yingying Zhang,Yinan Jiang,Zhu Zhu,Xinrui Xu,Hui Yang
Microplastic pollution, especially microfibers (MFs), presents a critical global environmental challenge in natural water bodies. Yet, research on the toxic effects of MFs, particularly during early fish development, is limited. This study aimed to investigate MFs' toxic effects and mechanisms on early-stage zebrafish. Zebrafish embryos were exposed to varying concentrations of polyacrylonitrile microfibers (PanMfs) for 7 days. Results revealed PanMfs adhering to the embryos' surface, with higher concentrations accelerating heart rate and causing pericardial edema in post-hatching larvae. Larvae ingested PanMfs, leading to their accumulation in the intestines and increased levels of reactive oxygen species (ROS) and mitochondrial quantity. Notably, lipid metabolism and calcium ion related signaling pathways underwent significant changes. Low concentration MFs affected glycometabolism pathways, with potential roles for aldob and cacng1a , exhibiting pronounced increases in ROS levels. High concentration of MFs had the most profound impact on signal transduction-related pathways, and possibly triggering micromitophagy and apoptosis in zebrafish intestinal epithelial cells through the Kras/MAPK signaling pathway, with potential roles for kras and mapk9 . Although ROS increase was somewhat alleviated, it resulted in decreased survival rates and restricted growth in high concentration of MFs group. These findings highlight the significant threat of MFs to the early survival of fish. MFs pollution prevention and control hold great significance in the conservation of fishery resources.
研究领域:
环境科学
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毒理学
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水生生物学
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渔业
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发育生物学
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DOI
PubMed
高影响因子
Reproductive Biology
·
2018
·
IF 1.446
Zhen Luo,Wenli Luo,Shaohua Li,Sen Zhao,Takami Sho,Xue Xu,Jing Zhang,Weina Xu,Jianxiong Xu
Intrauterine growth restriction (IUGR) remains a significant obstacle in pig production; however, information regarding the relationship between reactive oxygen species (ROS)-induced placental dysfunction and IUGR is still unknown. This study aimed to explore the placental redox status, mitochondrial content, cellular progression, and mitogen-activated protein kinase (MAPK) pathways in IUGR. Placental tissues were collected from normal intrauterine gestation (NIUG) and IUGR fetuses at delivery. Compared with the NIUG, placental ROS production, lipid peroxidation , and DNA damage were increased in IUGR. Placental mitochondrial DNA (mtDNA) content and mtDNA-encoded gene expression decreased in IUGR. Moreover, p21 phosphorylation increased, cyclin E expression decreased in IUGR cases, which showed senescence characteristics. Analysis of signaling pathways showed that the ERK1/2 phosphorylation increased whereas the p38 and JNK phosphorylation decreased in IUGR. In cultured porcine trophectoderm (pTr) cells, exogenous H 2 O 2 increased intracellular ROS production, decreased cell viability in a dose-dependent manner. Cell cycle distribution was found to arrest in S and G2/M phases. Our findings suggested that IUGR was associated with greater placental ROS and oxidative injury, which might be a factor that resulted in lower mitochondrial content, microvilli loss and senescence, and activation of MAPK pathways.
研究领域:
动物科学
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生殖生物学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）