RESUMO
The reproduction toxicity of pubertal exposure to Microcystin-LR (MC-LR) and the underlying mechanism needs to be further investigated. In the current study, pubertal male ICR mice were intraperitoneally injected with 2⯵g/kg MC-LR for four weeks. Pubertal exposure to MC-LR decreased epididymal sperm concentration and blocked spermatogonia proliferation. In-vitro studies found MC-LR inhibited cell proliferation of GC-1 cells and arrested cell cycle in G2/M phase. Mechanistically, MC-LR exposure evoked excessive reactive oxygen species (ROS) and induced DNA double-strand break in GC-1 cells. Besides, MC-LR inhibited DNA repair by reducing PolyADP-ribosylation (PARylation) activity of PARP1. Further study found MC-LR caused proteasomal degradation of SIRT6, a monoADP-ribosylation enzyme which is essential for PARP1 PARylation activity, due to destruction of SIRT6-USP10 interaction. Additionally, MG132 pretreatment alleviated MC-LR-induced SIRT6 degradation and promoted DNA repair, leading to the restoration of cell proliferation inhibition. Correspondingly, N-Acetylcysteine (NAC) pre-treatment mitigated the disturbed SIRT6-USP10 interaction and SIRT6 degradation, causing recovered DNA repair and subsequently restoration of cell proliferation inhibition in MC-LR treated GC-1 cells. Together, pubertal exposure to MC-LR induced spermatogonia cell cycle arrest and sperm count reduction by oxidative DNA damage and simultaneous SIRT6-mediated DNA repair failing. This study reports the effect of pubertal exposure to MC-LR on spermatogenesis and complex mechanism how MC-LR induces spermatogonia cell proliferation inhibition.
Assuntos
Toxinas Marinhas , Microcistinas , Sirtuínas , Espermatogônias , Animais , Masculino , Camundongos , Apoptose , Proliferação de Células , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Reparo do DNA , Toxinas Marinhas/metabolismo , Toxinas Marinhas/toxicidade , Camundongos Endogâmicos ICR , Microcistinas/metabolismo , Microcistinas/toxicidade , Sêmen , Sirtuínas/efeitos dos fármacos , Sirtuínas/metabolismo , Espermatogônias/efeitos dos fármacos , Espermatogônias/metabolismoRESUMO
Damage of reactive oxygen species to various molecules such as DNA has been related to many chronic and degenerative human diseases, aging, and even cancer. 8-Oxo-7,8-dihydroguanine (OG), the most significant oxidation product of guanine (G), has become a biomarker of oxidative stress as well as gene regulation. The positive effect of OG in activating transcription and the negative effect in inducing mutation are a double-edged sword; thus, site-specific quantification is helpful to quickly reveal the functional mechanism of OG at hotspots. Due to the possible biological effects of OG at extremely low abundance in the genome, the monitoring of OG is vulnerable to signal interference from a large amount of G. Herein, based on rolling circle amplification-induced G-triplex formation and Thioflavin T fluorescence enhancement, an ultrasensitive strategy for locus-specific OG quantification was constructed. Owing to the difference in the hydrogen-bonding pattern between OG and G, the nonspecific background signal of G sites was completely suppressed through enzymatic ligation of DNA probes and the triggered specificity of rolling circle amplification. After the signal amplification strategy was optimized, the high detection sensitivity of OG sites with an ultralow detection limit of 0.18 amol was achieved. Under the interference of G sites, as little as 0.05% of OG-containing DNA was first distinguished. This method was further used for qualitative and quantitative monitoring of locus-specific OG in genomic DNA under oxidative stress and identification of key OG sites with biological function.
Assuntos
DNA , Guanina , Humanos , DNA/genética , Estresse Oxidativo , Espécies Reativas de Oxigênio , Técnicas de Amplificação de Ácido NucleicoRESUMO
BACKGROUND: Perfluorohexane sulfonate (PFHxS) is a frequently detected per- and polyfluoroalkyl substance in most populations, including in individuals who are pregnant, a period critical for early life development. Despite epidemiological evidence of exposure, developmental toxicity, particularly at realistic human exposures, remains understudied. OBJECTIVES: We evaluated the effect of gestational exposure to human-relevant body burden of PFHxS on fetal and placental development and explored mechanisms of action combining alternative splicing (AS) and gene expression (GE) analyses. METHODS: Pregnant ICR mice were exposed to 0, 0.03, and 0.3µg/kg/day from gestational day 7 to day 17 via oral gavage. Upon euthanasia, PFHxS distribution was measured using liquid chromatography-tandem mass spectrometry. Maternal and fetal phenotypes were recorded, and histopathology was examined for placenta impairment. Multiomics was adopted by combining AS and GE analyses to unveil disruptions in mRNA quality and quantity. The key metabolite transporters were validated by quantitative real-time PCR (qRT-PCR) for quantification and three-dimensional (3D) structural simulation by AlphaFold2. Targeted metabolomics based on liquid chromatography-tandem mass spectrometry was used to detect amino acid and amides levels in the placenta. RESULTS: Pups developmentally exposed to PFHxS exhibited signs of intrauterine growth restriction (IUGR), characterized by smaller fetal weight and body length (p<0.01) compared to control mice. PFHxS concentration in maternal plasma was 5.01±0.54 ng/mL. PFHxS trans-placenta distribution suggested dose-dependent transfer through placental barrier. Histopathology of placenta of exposed dams showed placental dysplasia, manifested with an attenuated labyrinthine layer area and deescalated blood sinus counts and placental vascular development index marker CD34. Combined GE and AS analyses pinpointed differences in genes associated with key biological processes of placental development, proliferation, metabolism, and transport in placenta of exposed dams compared to that of control dams. Further detection of placental key transporter gene expression, protein structure simulation, and amino acid and amide metabolites levels suggested that PFHxS exposure during pregnancy led to impairment of placental amino acid transportation. DISCUSSION: The findings from this study suggest that exposure to human-relevant very-low-dose PFHxS during pregnancy in mice caused IUGR, likely via downregulating of placental amino acid transporters, thereby impairing placental amino acid transportation, resulting in impairment of placental development. Our findings confirm epidemiological findings and call for future attention on the health risk of this persistent yet ubiquitous chemical in the early developmental stage and provide a new approach for understanding gene expression from both quantitative and qualitative omics approaches in toxicological studies. https://doi.org/10.1289/EHP13217.
Assuntos
Fluorocarbonos , Placentação , Humanos , Gravidez , Camundongos , Animais , Feminino , Placenta , Processamento Alternativo , Camundongos Endogâmicos ICR , Fluorocarbonos/toxicidade , Fluorocarbonos/metabolismo , Alcanossulfonatos/metabolismo , Alcanossulfonatos/farmacologia , Retardo do Crescimento Fetal/metabolismo , Retardo do Crescimento Fetal/patologia , Aminoácidos/metabolismo , Aminoácidos/farmacologia , Perfilação da Expressão GênicaRESUMO
Our previous study showed 1-Nitropyrene (1-NP) exposure disrupted testicular testosterone synthesis in mouse, but the exact mechanism needs further investigation. The present research found 4-phenylbutyric acid (4-PBA), an endoplasmic reticulum (ER) stress inhibitor, recovered 1-NP-induced ER stress and testosterone synthases reduction in TM3 cells. GSK2606414, a protein kinase-like ER kinase (PERK) kinase inhibitor, attenuated 1-NP-induced PERK-eukaryotic translation initiation factor 2α (eIF2α) signaling activation and downregulation of steroidogenic proteins in TM3 cells. Both 4-PBA and GSK2606414 attenuated 1-NP-induced steroidogenesis disruption in TM3 cells. Further studies used N-Acetyl-L-cysteine (NAC) as a classical antioxidant to explore whether oxidative stress-activated ER stress mediated 1-NP-induced testosterone synthases reduction and steroidogenesis disruption in TM3 cells and mouse testes. The results showed NAC pretreatment mitigated oxidative stress, and subsequently attenuated ER stress, particularly PERK-eIF2α signaling activation, and downregulation of testosterone synthases in 1-NP-treated TM3 cells. More importantly, NAC extenuated 1-NP-induced testosterone synthesis in vitro and in vivo. The current work indicated that oxidative stress-caused ER stress, particularly PERK-eIF2α pathway activation, mediates 1-NP-downregulated steroidogenic proteins and steroidogenesis disruption in TM3 cells and mouse testes. Significantly, the current study provides a theoretical basis and demonstrates the experimental evidence for the potential application of antioxidant, such as NAC, in public health prevention, particularly in 1-NP-induced endocrine disorder.
Assuntos
Antioxidantes , Testículo , Masculino , Camundongos , Animais , Testículo/metabolismo , Antioxidantes/metabolismo , Fator de Iniciação 2 em Eucariotos/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Testosterona/metabolismo , Estresse Oxidativo , Acetilcisteína/farmacologia , Acetilcisteína/metabolismoRESUMO
Heavy metal cadmium (Cd), a classical environmental pollutant, causes placental apoptosis and fetal growth restriction (FGR), whereby the mechanism remains unclear. Here, our human case-control study firstly showed that there was a positive association of Parkin mitochondrial translocation, MCL-1 reduction, placental apoptosis, and all-cause FGR. Subsequently, Cd was administered to establish in vitro and in vivo models of placental apoptosis or FGR. Our models demonstrated that Parkin mitochondrial translocation was observed in Cd-administrated placental trophoblasts. Meaningfully, Parkin siRNA (siR) dramatically mitigated Cd-triggered apoptosis in placental trophoblasts. Mdivi-1 (M-1), an inhibitor for Parkin mitochondrial translocation, mitigated Cd-induced apoptosis in placental trophoblasts, which further ameliorated the effect of attenuated placental sizes in Cd-exposed mice. Furthermore, the interaction of MCL-1 with Parkin or Ub in Cd-stimulated cells was stronger than that in controls. MG132, an inhibitor for proteasome, abolished MCL-1 degradation in Cd-stimulated cells. Importantly, Parkin siR and M-1 memorably abolished the ubiquitin-dependent degradation of MCL-1 in placental trophoblasts. Interestingly, mito-TEMPO and melatonin, two mitochondria-targeted antioxidants, obviously rescued Cd-caused mitochondrial membrane potential (MMP) decrease, Parkin mitochondrial translocation, MCL-1 degradation, and apoptosis in placental trophoblasts. In conclusion, cadmium induces placental apoptosis and FGR via mtROS-mediated Parkin-modulated degradation of MCL-1.
Assuntos
Retardo do Crescimento Fetal , Placenta , Animais , Apoptose , Cádmio/toxicidade , Estudos de Casos e Controles , Feminino , Retardo do Crescimento Fetal/induzido quimicamente , Camundongos , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Gravidez , Ubiquitina-Proteína Ligases/genéticaRESUMO
Di (2-ethyl-hexyl) phthalate (DEHP) is a widely used plasticizer. Maternal DEHP exposure inhibits cell proliferation and reduces placentas size, which associates with fetal growth restriction and adulthood diseases. However, the mechanism of placental cell proliferation inhibition by DEHP remains elusive. This study investigated the effect of DEHP on placental cell proliferation from cell cycle arrest. Utilizing in vitro and in vivo experiments, we investigated cell cycle arrest, DNA double-strand break (DSB) repair, genotoxic stress response, and micronuclei formation. Most DEHP metabolizes to mono (2-Ethylhexyl) phthalate (MEHP) and distributes to organs quickly, so MEHP and DEHP were used in cultured cell and animal experiments, respectively. Here, a double blocking mode for the proliferation inhibition of the placental cell was revealed. One is that the classical DSB repair pathways were suppressed, which arrested the cell cycle at the G2/M phase. The other is that DEHP stimulated an elevated level of progesterone, which blocked the cell cycle at metaphase by disrupting chromosome arrangement. These two sets of events facilitated micronuclei formation and resulted in cell proliferation inhibition. This findings provide a novel mechanistic understanding for DEHP to inhibit placental cell proliferation.
Assuntos
Dietilexilftalato , Ácidos Ftálicos , Animais , Dietilexilftalato/toxicidade , Feminino , Placenta , Plastificantes/toxicidade , Gravidez , ProgesteronaRESUMO
Cadmium (Cd), a noxious heavy metal, is widespread in the living environment. Gestational exposure to Cd at environmental dose has been shown to cause fetal growth restriction (FGR). However, the long-term effects and the mechanisms underlying environmental Cd exposure on glucose metabolism in offspring remain unclear. Here, we established a murine model to study the impacts of gestational exposure to environmental Cd on glucose metabolism at different life stages of offspring. Results demonstrated that the offspring mice developed hyperglycemia in puberty and impaired glucose tolerance in adulthood following maternal Cd exposure during gestation. Further mechanistic investigation showed that Cd exposure upregulated the expression of key proteins in hepatic gluconeogenesis, including p-CREB, PGC-1α and G6PC, in pubertal and adult offspring. In addition, we demonstrated that Cd exposure during pregnancy markedly elevated the level of oxidative stress-related proteins, including NOX2, NOX4 and HO-1, in the fetal liver. The effects of gestational exposure to N-acetylcysteine (NAC), a free-radical scavenging antioxidant, presented that NAC supplementation alleviated hepatic oxidative stress in fetuses, and thereby reversed hyperglycemia and glucose intolerance in mouse offspring. Collectively, our data suggested that gestational exposure to environmental Cd caused diabetes-like phenotypes via enhancing hepatic gluconeogenesis, which is associated with oxidative stress in fetal livers. This work provides new insights into the protective effects of antioxidants on fetal-originated diabetes triggered by environmental toxicants.
Assuntos
Diabetes Mellitus , Efeitos Tardios da Exposição Pré-Natal , Adulto , Animais , Cádmio/metabolismo , Cádmio/toxicidade , Diabetes Mellitus/metabolismo , Feminino , Humanos , Fígado/metabolismo , Camundongos , Estresse Oxidativo , Fenótipo , GravidezRESUMO
Cadmium (Cd), a well-known environmental pollutant, can lead to placental insufficiency and fetal growth restriction. However, the underlying mechanism is unknown. The purpose of our study is to explore the effect of Cd on placental angiogenesis and its mechanism using in vitro and in vivo models. Results found that gestational Cd exposure obviously decreased placental weight and impaired placental vascular development in mice. Correspondingly, Cd exposure evidently downregulated the expression of VEGF-A protein (a key indicator of angiogenesis) and progesterone receptor (PR) in placental trophoblasts. Further experiment showed that lentivirus PR overexpression reversed Cd-caused the reduction of VEGF-A level in human placental trophoblasts. In addition, Cd significantly reduced progesterone level, down-regulated the expression of key progesterone synthase (StAR, CYP11A1), and activated mitochondrial stress response and GCN-2/p-eIF2α signaling in placental trophoblasts. Additional experiment showed that GCN-2 siRNA pretreatment markedly alleviated Cd-activated mitochondrial stress response, restored Cd-downregulated the expression of CYP11A1, reversed Cd-reduced the level of progesterone and VEGF-A in human placental trophoblasts. Finally, our case-control study confirmed that impaired placental angiogenesis and reduced progesterone level occurred in all-cause small for gestational age placenta. Taken together, environmental exposure to Cd impairs fetal growth and placental angiogenesis via GCN-2-mediated mitochondrial stress.
Assuntos
Cádmio , Fator A de Crescimento do Endotélio Vascular , Animais , Cádmio/toxicidade , Estudos de Casos e Controles , Exposição Ambiental , Feminino , Desenvolvimento Fetal , Camundongos , Placenta , Gravidez , Trofoblastos , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
Cadmium (Cd), an environmental toxicant, is positively associated with fetal growth restriction (FGR). However, the mechanism by which gestational exposure to Cd induces FGR remains unclear. This study designed in vitro and in vivo experiments to explore the role of placental mitophagy in Cd-impaired fetal growth. Based on our case-control study, we also investigated the association of placental mitophagy with reduced progesterone (P4) level and all-cause FGR. We firstly found environmental Cd exposure lowered the P4 content in maternal sera, placentae and amnioticfluids of mice. The level of three mitochondrial P4 synthases, including StAR, CYP11A1 and 3ß-HSD, was also reduced in Cd-treated placentae. Furthermore, Cd triggered mitophagy, as determined by the degradation of two mitochondrial proteins HSP60 and COX IV, and the accumulation of co-localizations of TOM20 with LC3B or Parkin in placental trophoblasts. Correspondingly, Cd elevated mitochondrial Parkin level in placental trophoblasts. Mdivi-1, a mitophagy inhibitor, obviously attenuated Cd-induced reduction of placental P4 and FGR in mice. Moreover, mdivi-1 and Parkin siRNA (siR) markedly reversed Cd-caused P4 synthesis inhibition in human placental trophoblasts. Interestedly, the PERK/ATF4 signaling was activated in Cd-stimulated placental trophoblasts. PERK siR inhibited mitochondrial proteins degradation in Cd-stimulated placental trophoblasts. In particularly, mitophagy activation and P4 synthesis suppression occurred in small-for-gestational-age placentae based on our case-control study. Environmental Cd exposure induced FGR via activating PERK-regulated mitophagy and inhibiting P4 synthesis in placentaltrophoblasts. Furthermore, placental mitophagy was related to the reduced progesterone level and all-cause fetal growth restriction based on our case-control study. As above, placental mitophagy maybe the common mechanism of environmental toxicants-impaired fetal growth.
Assuntos
Retardo do Crescimento Fetal , Trofoblastos , Animais , Cádmio/toxicidade , Estudos de Casos e Controles , Feminino , Retardo do Crescimento Fetal/induzido quimicamente , Camundongos , Mitofagia , Placenta , GravidezRESUMO
The electrochemical methods for microRNA (miRNA) detection have received increasing attention because high portability and affordability of electrochemical biosensors may facilitate point-of-care quantitative detection of miRNAs. Among these biosensors, the homogenous label-free electrochemical biosensors for miRNAs are rarely reported due to the lack of a universal and efficient signal read-out-mode. A newly discovered G-triplex, 5'-CTGGGAGGGAGGGA-3' (denoted as G3), can specifically bind with methylene blue (MB), leading to a significant decrease of the diffusion current of MB. By using miRNAs as a driving force, a two-stage isothermal exponential amplification reaction was proposed to generate G3 through miRNAs. The generated G3 can combine with MB and produce observable current changes, which depend on the concentration of miRNAs. Therefore, a novel homogeneous label-free electrochemical biosensor for miRNA detection was successfully constructed. By choosing let-7a, the down-regulation of which is possibly associated with the over-expression of RAS and HMGA2 oncogenes, as a model, we discovered that this biosensor demonstrated excellent analytical performance in detecting let-7a, with an ultralow limit of detection (0.45 fM) and high specificity (discriminating one nucleotide variation). Moreover, the proposed biosensor was successfully applied in monitoring the expression levels of the low-abundant miRNAs in the human lung adenocarcinoma cell lines. This assay successfully verified the feasibility of G-triplex/MB as an efficient and sensitive probe for immobilization-free and label-free electrochemical detection of nucleic acids, which would greatly promote the rapid development of homogeneous label-free electrochemical biosensors.
Assuntos
Técnicas Biossensoriais/métodos , DNA/química , Técnicas Eletroquímicas/métodos , Azul de Metileno/química , MicroRNAs/análise , Células A549 , DNA/genética , Humanos , Limite de Detecção , MicroRNAs/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Conformação de Ácido Nucleico , Hibridização de Ácido Nucleico , Estudo de Prova de ConceitoRESUMO
BACKGROUND Type 2 diabetes mellitus (T2DM) and its comorbidities, including obesity, hypertension, and hyperlipidemia, are commonly associated with non-alcoholic fatty liver disease (NAFLD). Ganoderma lucidum polysaccharide (GDLP) is one of the central bioactive components in Ganoderma lucidum with anti-inflammatory, antioxidant, and hepatoprotective properties. However, the effect and mechanisms of GDLP in hepatic steatosis remain largely unknown. In the present study, we aimed to investigate the function of GDLP in hepatic steatosis and the underlying mechanism. MATERIAL AND METHODS In this study, male db/db mice were received with a high-fat diet (HFD) to investigate the effect of GDLP in T2DM-induced hepatic steatosis. The biological characteristics of the hepatic steatosis were evaluated through the detection of clinical indicators, including biochemical parameters, histopathology, and related cytokine levels. Additionally, the protein expression levels of Nrf2 (nuclear factor E2 (erythroid-derived 2)-related factor-2) signaling pathway were investigated by using western blotting and immunohistochemical staining. RESULTS The levels of food/water intake, body weight, fasting blood glucose, plasma lipids, urinary biomarkers, hepatic lipid accumulation, and tumor necrosis factor (TNF)-alpha were observably decreased in GDLP-treated db/db mice. Additionally, administration of GDLP increased the expression of various antioxidases, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), whereas it reduced the level of malonaldehyde (MDA). Furthermore, GDLP was significantly promoted protein expression level of Nrf2 and its downstream target gene HO-1 (heme oxygenase-1) while decreased TNF-alpha expression. CONCLUSIONS These results indicate that GDLP against T2DM-induced hepatic steatosis, oxidative stress, and inflammation by improving the Nrf2/HO-1 signaling pathway in db/db mice, suggesting the GDLP may serve as an effective strategy for in fatty liver treatment.
Assuntos
Fígado Gorduroso/tratamento farmacológico , Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Reishi/química , Animais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Camundongos , PolissacarídeosRESUMO
The impairments of gestational cadmium (Cd) exposure on testicular development and male fertility in offspring have been reported. Here, we investigated the effect of paternal low-concentration cadmium exposure on testicular development and spermatogenesis in offspring. Five-week-old male mice were exposed to cadmium chloride (100 mg/L) in drinking water for 20 weeks. Results presented that Cd did not affect the testicular histology and sperm count in mice. After mating with untreated females, pregnant mice and pups were then evaluated. No significant difference in the rate for successful pregnancy and the body weight of pups was observed in Cd-exposed mice compared to the controls. Male offspring were given with a chow and high-fat diet from postnatal day (PND) 35 to PND70. Our data indicated that high-fat diet obviously decreased No. of sperm in epididymides of adult offspring due to paternal Cd exposure. Testicular histology revealed that the percentage of seminiferous tubules in stages IX-XII and the atypical residual bodies positive tubules in CdH (paternal cadmium exposure and pubertal high-fat diet) group were higher than these in CdC (paternal cadmium exposure and pubertal chow diet) group. Further analysis demonstrated that high-fat diet markedly accelerated testicular apoptosis, as determined by TUNEL assay and immunostaining for cleaved caspase-3, in male offspring due to paternal Cd exposure. Collectively, high-fat diet exacerbates the damage of testicular development and spermatogenesis in offspring due to paternal cadmium exposure.
Assuntos
Cádmio/toxicidade , Exposição Dietética , Poluentes Ambientais/toxicidade , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Cloreto de Cádmio/toxicidade , Dieta , Feminino , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Túbulos Seminíferos , Espermatozoides/efeitos dos fármacosRESUMO
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 CdCl2 (5, 50 and 250ppm) throughout pregnancy through drinking water or intraperitoneally injected with CdCl2 (4.5mg/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.
Assuntos
Cádmio/toxicidade , Poluentes Ambientais/toxicidade , Retardo do Crescimento Fetal/induzido quimicamente , Troca Materno-Fetal , Placenta/efeitos dos fármacos , Zinco/metabolismo , Animais , Cádmio/sangue , Cádmio/farmacocinética , Proteínas de Transporte de Cátions/genética , Regulação para Baixo , Poluentes Ambientais/sangue , Poluentes Ambientais/farmacocinética , Feminino , Sangue Fetal/química , Fígado/metabolismo , Metalotioneína/genética , Camundongos , Placenta/metabolismo , Gravidez , Zinco/sangueRESUMO
OBJECTIVE: To explore the rationality and clinical significance for the old and new surgical-pathological staging in endometrial carcinoma. METHODS: The clinical profiles and prognostic particulars were analyzed retrospectively in 92 cases of endometrial carcinoma from June 2005 to June 2011 at Xiaoshan Hospital. And the old and new surgical-pathological staging methods were applied to observe their rationality and treatment prognosis. RESULTS: There was 72.8% (67/92) for clinical stage I in the old surgical-pathological staging while 7.6% (7/92) for clinical stage II and 19.7% (18/92) for clinical stage III. There was 85.9% (79/92) for clinical stage I in the new surgical-pathological staging, 3.3% (3/92) for clinical stage IIand 10.7% (10/92) for clinical stage III. The detection rate of cancer cell was 8.7% (8/92) in peritoneal fluid. The positive rate of pelvic lymph node was 12.9% (11/85). A period of survival rates were compared among P > 0.05 after 3 years and 5 years of IA, IB and IIA. There was no statistical significance; there were statistical significance between IB and IC periods (P < 0.05). The survival of deep myometrial invasion was significantly shorter than that of superficial muscle layer. The positive rate of abdominal aortic lymph node was 3.8% (1/26). Six patients with positive lymph nodes died postoperatively of cancer within 4 to 28 months. CONCLUSION: The new surgical-pathological staging is more objective, practical, simple and convenient than its old counterpart. Deep myometrial infiltration and positive lymph node are important prognostic factors of endometrial carcinoma. The positive rate of lymph node remains low in early low-risk endometrial carcinoma and routine excision of lymph node is of little significance.