Animals
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2023
·Vol. 13
·期 24
·3832
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IF 3
Hongmei Xu,Yueyue Li,Qiao Li,Zifeng Ma,Shi Yin,Honghong He,Yan Xiong,Xianrong Xiong,Daoliang Lan,Jian Li,Wei Fu
Simple SummaryIn recent years, authoritative journals have consistently reported DHODH’s critical role in resistance to ferroptosis, significantly advancing the research on related mechanisms. Nevertheless, the nucleotide sequence of the yakDHODHgene remains unknown, and its involvements in ferroptosis processes in yak cells remain elusive. Therefore, in the present study, we cloned the coding region of the yakDHODHgene, and revealed its high conservation in mammals. Furthermore, by using a bisphenol S (BPS)-induced ferroptosis model, we confirmed the role of theDHODHgene in mitigating ferroptosis in yak skin fibroblasts (YSFs) derived from a three-mouth-old fetus. This study offers theoretical support for further exploring the functions of the yakDHODHgene and partially elucidating the molecular mechanisms underlying ferroptosis.AbstractDihydroorotate dehydrogenase (DHODH) is a rate-limiting enzyme ofde novobiosynthesis of pyrimidine. Although the involvement of DHODH in resisting ferroptosis has been successively reported in recent years, which greatly advanced the understanding of the mechanism of programmed cell death (PCD), the genetic sequence of the yakDHODHgene and its roles in ferroptosis are still unknown. For this purpose, we firstly cloned the coding region sequence ofDHODH(1188 bp) from yak liver and conducted a characterization analysis of its predictive protein that consists of 395 amino acids. We found that the coding region of the yakDHODHgene presented high conservation among species. Second, the expression profile of theDHODHgene in various yak tissues was investigated using RT-qPCR. The results demonstrated thatDHODHwas widely expressed in different yak tissues, with particularly high levels in the spleen, heart, and liver. Third, to investigate the involvement ofDHODHin regulating ferroptosis in cells, yak skin fibroblasts (YSFs) were isolated from fetuses. And then, bisphenol S (BPS) was used to induce thein vitroferroptosis model of YSFs. We observed that BPS decreased the cell viability (CCK8) and membrane potential (JC-1) of YSFs in a dose-dependent manner and induced oxidative stress by elevating reactive oxygen species (ROS). Simultaneously, it was evident that BPS effectively augmented the indicators associated with ferroptosis (MDA and BODIPY staining) and reduced GSH levels. Importantly, the co-administration of Ferrostatin-1 (Fer), a potent inhibitor of ferroptosis, significantly alleviated the aforementioned markers, thereby confirming the successful induction of ferroptosis in YSFs by BPS. Finally, overexpression plasmids and siRNAs of the yakDHODHgene were designed and transfected respectively into BPS-cultured YSFs to modulateDHODHexpression. The findings revealed thatDHODHoverexpression alleviated the occurrence of BPS-induced ferroptosis, while interference ofDHODHintensified the ferroptosis process in YSFs. In summary, we successfully cloned the coding region of the yakDHODHgene, demonstrating its remarkable conservation across species. Moreover, using BPS-induced ferroptosis in YSFs as the model, the study confirmed the role of theDHODHgene in resisting ferroptosis in yaks. These results offer valuable theoretical foundations for future investigations into the functionality of the yakDHODHgene and the underlying mechanisms of ferroptosis in this species.Keywords:yak;DHODHgene;fetal fibroblasts;ferroptosis;Bisphenol S
研究领域:
分子生物学
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细胞生物学
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遗传学
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PubMed
高影响因子
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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PubMed
高影响因子
MICROCHIMICA ACTA
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2023
·Vol. 190
·期 11
·1-11
·
IF 5.7
Li Shuang-Ning,You Ya,Liu Bo,Jiang Xin-Yu,Yu Jin-Gang
A novel nanocomposite material, ferric vanadate intertwined multi-walled carbon nanotubes (FeV/MWCNTs), has been designed which was drop-coated onto a glassy carbon electrode (GCE). The constructed sensor was used for the sensitive determination of uric acid (UA) in fetal bovine serum (FBS) and human serum (HS). A series of characterization and electrochemical tests showed that the ultrasound-assisted assembly of FeV with MWCNTs not only overcame the disadvantages of low conductivity and easy (unwanted) aggregation, but also avoided the decrease in effective surface area due to the severe aggregation of each individual raw material. The fabricated FeV/MWCNTs nanocomposites exhibited higher conductivity, larger effective surface area, and better electrocatalytic activity. In addition, under optimized conditions, the developed electrochemical sensor FeV/MWCNTs/GCE has a lower limit of detection (LOD, 0.05 µM; Ep = 0.268 V vs. Ag/AgCl) and wider linear range (0.20–100 µM), which can satisfy the criteria of trace UA detection. The results of UA determination in FBS (recovery = 95.5–103%; RSD ≤ 3.1%) and HS (recovery = 95.5–103%; RSD ≤ 4.3%) further validated the feasibility of FeV/MWCNTs-based electrochemical sensors for the determination of UA in biological fluids.
研究领域:
分析化学
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生物医学工程
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PubMed
高影响因子
Scientific Reports
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2024
·Vol. 14
·期 1
·1-14
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IF 3.8
Bian Lijun,Su Xinglin,Wang Jialu
Carbon cloth (CC) was electrochemically activated using three electrochemical methods in different electrolytes. The gases released during the activation process etched the surface of the CC, thereby increasing its surface area of the activated CC (FCC). Moreover, functional groups such as oxygen-containing groups and N-doping have been introduced. The quantity and type of functional groups introduced during the activation process were related to the anions in the solution. FCC electrodes were used to construct electrochemical sensors for the simultaneous determination of ascorbic acid (AA), dopamine (DA), and uric acid (UA). The PFCC electrode activated by advanced cyclic voltammetry in (NH 4 ) 2 HPO 4 showed linear ranges for AA, DA, and UA concentrations of 0.1 to 2.1 mM, 0.5 to 11 µM, and 0.5 to 11 µM, respectively. The detection limits are 72.93, 0.22, and 0.42 µM, respectively. The good flexibility the PFCC electrode made it suitable for the preparation of flexible sensors. The simultaneous determination of AA, DA, and UA in fetal bovine serum showed a reliable recovery ratio. This study provides a simple and green approach for activating carbon cloth and constructing flexible electrochemical sensors with the potential to simultaneously detect AA, DA, and UA.
研究领域:
分析化学
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生物医学工程
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PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2021
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IF 6.291
Min Kang,Jie Luo,Ling Zhao,Fei Shi,Gang Ye,Xiaoli He,Suqi Hao,Dan Yang,Helin Chen,Hongrui Guo,Yinglun Li,Huaqiao Tang
Nano-copper (nano-Cu) is widely used in the pharmaceutical field as well as a feed additive for animals owing to its unique physicochemical characteristics and bioactivities. In our previous study, nano-Cu was found to hamper fetal development; however, the toxicity of nano-Cu and its effects in placental function have not been elucidated. Therefore, we investigated the toxic effects of nano-Cu using rat placenta. Pregnant Sprague-Dawley rats were orally exposed to different copper sources from the third day of gestation (GD 3) to GD 18. We found that nano-Cu (180 mg/kg) and CuCl 2 .2 H 2 O increased the accumulation of copper. Besides, nano-Cu and CuCl 2 .2 H 2 O disrupted the placental morphology and induced oxidative stress. Micro-copper (micro-Cu) caused similar toxicity in the placenta, but its effects were weaker than that of nano-Cu and CuCl 2 .2 H 2 O. In addition, exposure to nano-Cu (180 mg/kg) and CuCl 2 .2 H 2 O induced inflammation in the rat placenta. Furthermore, nano-Cu, micro-Cu, and CuCl 2 .2 H 2 O upregulated the expression of the autophagy-related proteins, Beclin-1 and LC3 II/ LC3 I, and downregulated that of p62. Moreover, nano-Cu, micro-Cu, and CuCl 2 .2 H 2 O downregulated the protein expression of PI3K, p-AKT/AKT, and p-mTOR/mTOR in rat placentas, whereas the protein expression of p-AMPK/AMPK was upregulated. Taken together, our data indicated that prenatal exposure to nano-Cu induced autophagy via the PI3K/AKT/mTOR and AMPK/mTOR pathways, which associated with oxidative stress and inflammation in rat placenta.
研究领域:
毒理学
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药理学
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生殖生物学
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PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
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IF 6.2
Zijie Zhou,Yan Zhang,Yan Liu,Quanshu Wang,Shouhai Jiao,Shuping Zhang,Xiaolu Li,Li Sun
Maternal anemia has been identified as a contributing factor to adverse reproductive outcomes associated with cadmium (Cd) exposure, a common heavy metal. Our recent findings suggest that inhibited erythroid differentiation and enucleation also play significant roles in the direct embryonic toxicity resulting from maternal Cd exposure. However, the effects of Cd exposure on lipid metabolism remodeling, which is essential for physiological erythropoiesis, remain poorly understood. In the present study, pregnant mice were administered low doses of CdCl 2 via oral exposure from early to late gestation to mitigate Cd-induced maternal anemia. Compared to vehicle-treated controls, embryos from Cd-treated mice exhibited a slight decrease in weight, though without signs of atrophy. Consistent with our previous observations, fetal livers from Cd-exposed embryos demonstrated a dose-dependent inhibition of erythroid differentiation, as confirmed by ex vivo analysis. Notably, an intrinsic decrease in lipid peroxidation during erythroid differentiation was observed in the bone marrow and fetal livers of vehicle-treated mice, attributed to diminished lipid content. In contrast, this decrease in lipid peroxidation was absent in fetal liver erythroblasts from Cd-treated mice, where an increase in lipid peroxidation was instead noted. These findings elucidate a potential mechanism, lipid peroxidation, underlying Cd-induced embryonic toxicity.
研究领域:
毒理学
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生殖生物学
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血液学
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高影响因子
FASEB JOURNAL
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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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PubMed
高影响因子
JOURNAL OF ENVIRONMENTAL MANAGEMENT
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2025
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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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PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
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IF 8.2
Ying Yu,Yuan Cheng,Shiwei Xu,Wanyun Song,Mingming Wang,Liqiang Song,Kejia Zhu,Tao Zhang
Noninvasive prenatal diagnosis based on fetal cells (cell-based NIPD) offers a safer alternative to traditional invasive procedures but remains limited by the low abundance of fetal nucleated red blood cells (FNRBCs) in maternal circulation and the inefficiency of current isolation techniques. Here, we present a functionalized interventional system for in situ hematologic cell capture (FISHC) directly from peripheral blood, eliminating the need for blood withdrawal and ex vivo processing. FISHC features a carboxybetaine methacrylate (CBMA)-functionalized medical wire with immobilized FNRBC-specific antibodies, enabling high-specificity cell capture under physiological conditions. In vivo validation in a pregnant monkey model confirms its feasibility for efficient and minimally invasive fetal cell retrieval. FISHC represents a paradigm shift in cell-based NIPD and holds promise for broader biomedical applications, including circulating tumor cell detection and real-time liquid biopsy technologies.
研究领域:
医学工程
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生殖健康
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生物医学工程
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PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2025
·
IF 11.3
Qigang Fan,Yi Sun,Qingjun Shen,Yuxin Wang,Jisheng Nie,Yanbing Lin,Shuaishuai Xing,Yan Li,Benhong Xu,Jianjun Liu,Xiaoting Shen,Guangbo Qu,Jun Xie,Liqin Zeng,Huidong Zhang
Li exposure is becoming a new prominent major issue in energy-environment-health field. However, its reproductive health risk has been less explored. In this study, we find that exposure to 28-fold REED ( r eally e nvironmental e xposure d ose) of Li is enough to induce mouse miscarriage by altering the structures and functions of placenta. Exposure to ≥ 5.6-fold REED of Li is enough to alter the structure and functions of ovary and placenta, and exposure to ≥ 28-fold REED of Li alters fetus morphology and uterus functions, showing a susceptibility to Li exposure as the order ovary > placenta > fetus > uterus. Some characteristics (such as AMH (anti-müllerian hormone) levels in serum, the mRNA levels of Pgr (progesterone receptor) and Nr2f2 in placenta, and the mRNA levels of Cyp19A1 and Sohlh2 in Ovary) are significantly altered with exposure to 5.6-fold REED of Li, which could be used as sensitive targets to predict reproductive health risk with Li exposure. Moreover, the doses of Li in clinical Li treatment (28- or 56-fold REED of Li) should be more cautious, especially for women. Collectively, this study identifies Li exposure as a new risk factor for female reproductive healthy in energy-environment-health field, which deserves the critical attention by governments, enterprises, and hospitals.
研究领域:
环境科学
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毒理学
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生殖生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
·
IF 4.7
Shuangping Ma,Xianting Liu,Yiran Qin,Yilong Wang,Yu Feng,Binfeng Cheng,Lei Wang
Sickle cell disease (SCD) and β-thalassemia are autosomal recessive genetic disorders caused by abnormal synthesis of β-globin chains. Reversing the transition of fetal-to-adult hemoglobin after birth shows great potential in the treatment of these disorders. Here, we identified an RNA-binding protein, RBM3, as a novel HbF (HbF, α 2 γ 2 ) suppressor. Specifically, downregulation of RBM3 in the erythroid progenitor cell line HUDEP-2 robustly induced γ-globin expression at both the mRNA and protein levels, with a slight impact on β-globin levels. Conversely, overexpression of RBM3 in HUDEP-2 cells led to a marked reduction in γ-globin expression. According to the previous study, we introduced specific inhibitors targeting FAK and Src to block RBM3 protein synthesis. Surprisingly, treatment with the FAK inhibitor resulted in a significant increase in γ-globin expression, whereas the Src inhibitor had little effect. Mechanistically, RBM3 depletion accelerated the degradation of BCL11A protein at the post-transcriptional level, without affecting its mRNA stability. Moreover, RBM3 silencing restricted the overall translation efficiency while selectively lifting the ratio of γ-globin mRNA in polysomes. Importantly, downregulation of RBM3 did not impair erythropoiesis progression, suggesting a safe and effective therapeutic strategy for SCD and β-thalassemia. Our findings identify RBM3 as a negative regulator of HbF expression and reveal it as a novel molecular target for modulating the fetal-to-adult hemoglobin switch, holding great promise for the treatment of SCD and β-thalassemia.
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高影响因子
Environmental Science & Technology Letters
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2024
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IF 8.9
Xiaojia Chen,Jingzhi Yao,Yu Ma,Yuanyuan Fang,Wenxin Wang,Xiaojun Deng,Ling Tan,Yi-Jun Fan,Mingliang Fang
Assessing the placental transfer efficiency of toxic chemicals remains challenging. Here, a robust machine learning (ML) model was developed to predict the human fetal–maternal blood concentration ratio (F/M) at the exposomic level. By curating one of the largest F/M data sets, we evaluated a series of prediction models using a combination of 12 ML algorithms and four molecular fingerprints. The long short-term memory (LSTM) model with retraining optimization works as the best performer, displayed robust accuracy (R2train = 0.91, R2test = 0.68), and was subsequently applied to our previously developed risk-based Human Exposome and Metabolite Database (HExpMetDB). The fetal hazard quotient (FHQ) was assessed using the predicted F/M ratios, probabilistic exposure dose, and toxicity index. From the top 1000 prioritized chemicals via FHQs ranking, we randomly selected four candidates (triethyl phosphate, benzotriazole, oxybenzone, and dichlormid) to perform in vivo experiments. All four chemicals exhibited transplacental potential (F/M ratio >0.3) as new possible chemicals of concern, demonstrating the accuracy of the predictive model. The Shapley additive explanation (SHAP) method revealed the top 10 key structural fragments related to the transplacental transfer efficiency. We believe that the prediction model can serve as an effective tool to screen potential risk compounds of fetal exposure.
研究领域:
毒理学
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计算生物学
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生殖医学
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高影响因子
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