PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2024
·
IF 4.2
Chaojin Si,Hongjun Yang,Xiaoyan Wang,Qiaoxin Wang,Min Feng,Huayue Li,Yuqi Feng,Jiayuan Zhao,Ying Liao
Beta-cypermethrin (β-CYP) consists of four chiral isomers, acting as an environmental estrogen and causing reproductive toxicity, neurotoxicity, and dysfunctions in multiple organ systems. This study investigated the toxic effects of β-CYP, its isomers, metabolite 3-phenoxybenzoic acid (3-PBA), and 17β-estradiol (E2) on HTR-8/SVneo cells. We focused on the toxic mechanisms of β-CYP and its specific isomers. Our results showed that β-CYP and its isomers inhibit HTR-8/SVneo cell proliferation similarly to E2, with 100 μM 1S-trans-αR displaying significant toxicity after 48 h. Notably, 1S-trans-αR, 1R-trans-αS, and β-CYP were more potent in inducing apoptosis and cell cycle arrest than 1R-cis-αS and 1S-cis-αR at 48 h. AO/EB staining and flow cytometry indicated dose-dependent apoptosis in HTR-8/SVneo cells, particularly at 100 μM 1R-trans-αS. Scratch assays revealed that β-CYP and its isomers variably reduced cell migration. Receptor inhibition assays demonstrated that post-ICI 182780 treatment, which inhibits estrogen receptor α (ERα) or estrogen receptor β (ERβ), β-CYP, its isomers, and E2 reduced HTR-8/SVneo cell viability, whereas milrinone, a phosphodiesterase 3 A (PDE3A) inhibitor, increased viability. Molecular docking studies indicated a higher affinity of β-CYP, its isomers, and E2 for PDE3A than for ERα or ERβ. Consequently, β-CYP, its isomers, and E2 consistently led to decreased cell viability. Transcriptomics and RT-qPCR analyses showed differential expression in treated cells: up-regulation of Il24 and Ptgs2 , and down-regulation of Myo7a and Pdgfrb , suggesting the PI3K-AKT signaling pathway as a potential route for toxicity. This study aims to provide a comprehensive evaluation of the cytotoxicity of chiral pesticides and their mechanisms.
研究领域:
毒理学
·
生殖生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR ENDOCRINOLOGY
·
2025
·
IF 3.6
Lanlan Cheng,Jie Zhang,Yungai Xiang,Li Tan
Spontaneous abortion (SA) refers to the loss of a pregnancy without external intervention. The runt-related transcription factor 3 (RUNX3) is associated with gestational disorders in view of previous studies. However, RUNX3 has not been reported in SA. RUNX3 is significantly upregulated in the placental villi of abortion patients based on the GSE123719 microarray data. Herein, we further validated and found that the expression of RUNX3 in placental villi of SA women was higher than those of induced abortion (IA) women. In vitro , we constructed human RUNX3 overexpression or interference adenovirus vectors to modulate RUNX3 expression in trophoblast cells. Our findings revealed that RUNX3 overexpression accelerated trophoblast cell ferroptosis, while RUNX3 knockdown alleviated erastin-induced ferroptosis. Subsequently, the dual luciferase reporter assay was performed to confirm that RUNX3 bound to the GDF15 promoter to transcriptionally repress GDF15 transcriptional activity. Importantly, GDF15 attenuated the pro-ferroptosis effects of RUNX3 on HTR-8/SVneo cells. In vivo , mouse RUNX3 interference adenovirus vectors were used to silence RUNX3 in mice. The results presented that the reduction of RUNX3 inhibited embryo adsorption rate in SA mice, involving ferroptosis and the interaction between RUNX3 and GDF15. Taken together, this study established that RUNX3 advanced SA progression by enhancing trophoblast ferroptosis via transcriptionally repressing GDF15. These findings may provide novel therapeutic strategies for SA management.
研究领域:
分子生物学
·
细胞生物学
·
生殖医学
·
遗传学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Cardiovascular Medicine
·
2022
·
IF 5.846
Xianli Wang,Shaokun Yu,Yuting Jian,Hongmin Pan,Jiannan Guo,Jian Wu,Wei Guo
Extravillous trophoblast invasion disorder caused by oxidative stress is involved in the pathogenesis of preeclampsia (PE). In order to identify whether hydrogen sulfide (H 2 S) can prevent oxidative stress injury in extravillous trophoblasts. HTR-8/SVneo cells were detected by H 2 S inhibiting H 2 O 2 induced oxidative mitochondrial damage. Reactive oxygen species (ROS) were detected, as well as malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD). JC-1 detected the potential of the mitochondrial membrane in this experiment. Then to detect the expression level of the apoptosis-inducing protein B-cell lymphoma-2 (Bcl-2) associated X protein (Bax), caspase 3, p53, p-p53, the apoptosis-inhibiting protein Bcl-2, PRAP, and the mitochondria fission protein Drp1, p-Drp1. CCK-8 assay, it was demonstrated that cell proliferation in the NaHS group was significantly higher than that in the Mod group, indicating that H 2 S may induce cell proliferation. Transwell assay elucidated that cell invasion in the NaHS group was recovered compared to the Mod group. ROS concentration no matter in cells or mitochondria was decreased by NaHS, which we could get from the comparison between the Mod group, PAG group, and NaHS group. The concentration of MDA was significantly lower in the NaHS group, and the concentration of SOD was extremely high in the NaHS group. Utilized JC-1 to detect mitochondrial membrane potential and found that cells from the NaHS group had a stable potential while cells from the Mod group and PAG group partly lost their potential, which could demonstrate that NaHS could maintain mitochondrial membrane potential. The western blot results revealed that p-Drp1 had a significant decline in the NaHS group, which means mitochondria fission was decreased in the NaHS group. The expression level of Bax and caspase 3 was significantly lower than in the Mod group and PAG group, and the expression level of Bcl-and PRAP was significantly higher in the NaHS group. That could prove that NaHS protect HTR-8/SVneo cell by inhibiting cell apoptosis. These promising results show that H 2 S elicits its effects on cell apoptosis by decreasing ROS concentration, maintaining mitochondrial membrane stability, and promoting apoptosis-inhibiting protein expression in cells.
研究领域:
妇产科学
·
细胞生物学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Human Cell
·
2024
·
IF 3.4
Zhang Ke,Zhang Hailing,Wang Bing,Gao Shanshan,Sun Caiping,Jia Cong,Cui Jinquan
Abnormal functions of trophoblast cells are associated with the pathogenesis of preeclampsia (PE). Nuclear receptor subfamily 2 group F member 1 (NR2F1) acts as a transcriptionally regulator in many diseases, but its role in PE remains unknown. Hypoxia/reoxygenation (H/R)-stimulated HTR-8/SVneo cells were used to mimic PE injury in vitro. NR2F1 overexpression alleviated trophoblast apoptosis, as evidenced by the decreased number of TUNEL-positive cells and the downregulation of caspase 3 and caspase 9 expression in cells. NR2F1 overexpression increased the invasion and migration ability of HTR-8/SVneo cells, accompanied by increased protein levels of matrix metalloproteinase (MMP)-2 and MMP-9. mRNA-seq was applied to explore the underlying mechanism of NR2F1, identifying growth differentiation factor 15 (GDF15) as the possible downstream effector. Dual-luciferase reporter, ChIP-qPCR, and DNA pull-down assays confirmed that NR2F1 bound to the promoter of GDF15 and transcriptionally inhibited its expression. GDF15 overexpression increased apoptosis and decreased the ability of invasion and migration in HTR-8/SVneo cells expressing NR2F1. MAPK pathway was involved in the regulation of PE. Administration of p38 inhibitor, ERK inhibitor, and JNK inhibitor reversed the effect of simultaneous overexpression NR2F1 and GDF15 on trophoblast apoptosis, invasion, and migration. Our findings demonstrated that NR2F1 overexpression inhibited trophoblast apoptosis and promoted trophoblast invasion and migration. NR2F1 might negatively regulate GDF15 expression by binding to its promoter region, which further inhibited MAPK signaling pathway in PE. Our study highlights that NR2F1 might sever as a potential target in PE. Graphical abstract
研究领域:
妇产科学
·
分子生物学
·
细胞生物学
·
转录调控
·
信号传导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
·
2022
·Vol. 78
·期 4
·777-791
·
IF 5.08
Li Ling,Bai Yu,Du Runyu,Tang Lei,Li Ling
Gestational diabetes mellitus (GDM) is a common pregnancy complication with a high incidence in women. Orphan nuclear receptor NUR77 is involved in regulating glucose metabolism. However, its role in GDM has not been fully elucidated yet. In this study, an animal model of GDM was established by feeding mice with a high-fat diet (HFD) before and during pregnancy. NUR77 expression was abnormally upregulated in placenta tissues of GDM mice. We performed gain- and loss-of-function studies of NUR77 in HTR-8/SVneo cells. Cells were incubated with 1 × 10 −6 M insulin for 48 h to induce insulin resistance (IR). The expression of NUR77 was downregulated in HTR-8/SVneo cells following IR induction. Overexpression of NUR77 promoted cell proliferation, migration, and invasion. Notably, NUR77 promoted glucose uptake and enhanced insulin sensitivity in vitro. NUR77 increased the ratio of p-insulin receptor β (IRβ) Tyr1361 /IRβ, p-insulin receptor substrate (IRS)-1 Tyr612 /IRS-1, p-Akt/Akt and decreased p-IRS-1 Ser307 /IRS-1, as well as lowered the expression of glucose transport protein type 1 (GLUT1) and elevated GLUT4. These results suggest the involvement of IRβ/IRS/Akt/GLUT4 signaling activation in the regulatory effects of NUR77 on IR in HTR-8/SVneo cells. Silencing of NUR77 displayed opposite effects. Besides, NUR77 enhanced the expression of autophagy-related protein Beclin 1 and the ratio of LC3II/LC3I. Further study demonstrated that the inhibitory effect of NUR77 on IR was partially attributed to the activation of autophagy. Therefore, we demonstrate that NUR77 enhances insulin sensitivity in HTR-8/SVneo cells likely through activating IRβ/IRS/Akt/GLUT4 pathway and regulating autophagy.
研究领域:
内分泌学
·
妇产科学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2020
·
IF 5.778
Jing Li,Xiao-jie Quan,Gang Chen,Jia-wei Hong,Qi Wang,Lin-lin Xu,Bing-hua Wang,Ze-hua Yu,Hong-Min Yu
Perfluorooctane sulfonic acid (PFOS), a persistent environmental pollutant, has been associated with decreased birth weight. The dysregulation of long non-coding RNA (lncRNA) H1 9 has been implicated in pregnancy complications such as intra-uterine growth retardation (IUGR), preeclampsia (PE), however, the expression and function of H19 in PFOS-exerted detrimental effects in the placenta remains to be unveiled. Here, we explored the role of H19 in PFOS-induced placental toxicity. Results showed that PFOS caused decreased cell growth in human HTR-8/SVneo cells. Expression of H19 was increased, while miR-19a and miR-19b expression were decreased in mice placenta tissues and in HTR-8/SVneo cells exposed to PFOS. A significant hypomethylation was observed at the H19 promoter in the placentas of mice that were gestational exposed to high dose of PFOS. H19 was confirmed to bind with miR-19a and miR-19b, targeting SMAD4 . Furthermore, H19 appeared to partially improve the cell growth of HTR-8/SVneo cells exposed to PFOS via upregulation of miR-19a and miR-19b. In summary, our findings revealed that H1 9/miR-19a and miR-19b/SMAD4 axis exerted important functions in PFOS-induced placenta cell toxicity.
研究领域:
毒理学
·
分子生物学
·
生殖健康
✓ 已验证
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2022
·
IF 10.753
Yiwei Fang,Zhiliang Chen,Jinyu Chen,Minqi Zhou,Yuanyao Chen,Rong Cao,Chunyan Liu,Kai Zhao,Min Wang,Huiping Zhang
Mono(2-ethylhexyl) phthalate (MEHP) is a metabolite of DEHP which is one of phthalic acid esters (PAEs) widely used in daily necessities. Moreover, MEHP has been proven to have stronger biological toxicity comparing to DEHP. In particular, several recent population-based studies have reported that intrauterine exposure to MEHP results in adverse pregnancy outcomes. To explore the mechanisms and metabolic biomarkers of MEHP exposure, we examined the metabolic status of HTR-8/Svneo cell lines exposed to different doses of MEHP (0, 1.25, 5.0, 20 μM). Global and dose–response metabolomics tools were used to identify metabolic perturbations and sensitive markers associated with MEHP. Only 22 metabolic features (accounted for <1 %) were significantly changed when exposed to 1.25 μM. However, when the exposure dose was increased to 5 or 20 μM, the number of significantly changed metabolic features exceeded 300 (approximately 10 %). In particular, amino acid metabolism, pyrimidine metabolism and glutathione metabolism were widely affected according to the enrich analysis of those significant altered metabolites, which has and have previously been reported to be closely related to fetal development. Moreover, 5′-UMP and N -acetylputrescine with the lowest effective concentrations (EC −10 = 0.1 μM and EC +10 = 0.11 μM, respectively) were identified as sensitive endogenous biomarkers of MEHP exposure.
研究领域:
毒理学
·
生殖生物学
·
代谢组学
✓ 已验证
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）