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Toxoplasma gondii infection in pregnant women may cause fetal anomalies; however, the underlying mechanisms remain unclear. The current study investigated whether T. gondii induces pyroptosis in human placental cells and the underlying mechanisms. Human placental trophoblast (BeWo and HTR-8/SVneo) and amniotic (WISH) cells were infected with T. gondii, and then reactive oxygen species (ROS) production, cathepsin B (CatB) release, inflammasome activation, and pyroptosis induction were evaluated. The molecular mechanisms of these effects were investigated by treating the cells with ROS scavengers, a CatB inhibitor, or inflammasome-specific siRNA. T. gondii infection induced ROS generation and CatB release into the cytosol in placental cells but decreased mitochondrial membrane potential. T. gondii-infected human placental cells and villi exhibited NLRP1, NLRP3, NLRC4, and AIM2 inflammasome activation and subsequent pyroptosis induction, as evidenced by increased expression of ASC, cleaved caspase-1, and mature IL-1ß and gasdermin D cleavage. In addition to inflammasome activation and pyroptosis induction, adverse pregnancy outcome was shown in a T. gondii-infected pregnant mouse model. Administration of ROS scavengers, CatB inhibitor, or inflammasome-specific siRNA into T. gondii-infected cells reversed these effects. Collectively, these findings show that T. gondii induces NLRP1/NLRP3/NLRC4/AIM2 inflammasome-dependent caspase-1-mediated pyroptosis via induction of ROS production and CatB activation in placental cells. This mechanism may play an important role in inducing cell injury in congenital toxoplasmosis.
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Inflamassomos , Toxoplasma , Camundongos , Animais , Humanos , Feminino , Gravidez , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Piroptose , Trofoblastos/metabolismo , Catepsina B/metabolismo , Catepsina B/farmacologia , Placenta/metabolismo , RNA Interferente Pequeno , Caspases/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Proteínas NLR/metabolismoRESUMO
Amodiaquine (AQ) is routinely prescribed as an anti-malarial drug. Here, we evaluated AQ-induced toxicity in the male reproductive system. Eighty adult male Sprague-Dawley rats were randomly divided into four groups that received distilled water (control) or daily doses of 5 mg/kg body weight, 10 mg/kg, or 15 mg/kg AQ for 2 weeks. Testes morphology was analyzed using hematoxylin-and-eosin staining, terminal dUTP nicked-end labeling (TUNEL), and immunostaining whereas protein expression was determined by Western blotting. AQ dose-dependently led to abnormal spermatogenesis. Disruption of the blood-testis barrier and increased germ cell apoptosis were observed in all three AQ-treated groups. Interestingly, AQ-induced damage of spermatogenesis recovered over time, based on the survival of promyelocytic leukemia zinc-finger (PLZF)-positive, undifferentiated spermatogonia. Serum levels of luteinizing hormone and testosterone, as well as testicular testosterone levels, were not significantly altered in AQ-treated groups compared with controls. Collectively, our study suggests that AQ exerts substantial acute side effects on the reproductive systems of adult male rats by inducing the apoptosis of differentiating spermatogenic cells and disruption of blood-testis barrier function.
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Amodiaquina/efeitos adversos , Barreira Hematotesticular/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Espermatogênese/efeitos dos fármacos , Espermatogônias/metabolismo , Amodiaquina/farmacologia , Animais , Barreira Hematotesticular/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Espermatogônias/patologiaRESUMO
To study the genetic variation leading to the arrest phenotype of pronuclear (PN) zygotes. We recruited a family characterized by recurrent PN arrest during in vitro fertilization (IVF) and intracytoplasmic sperm injection cycles (ICSI) and performed whole-exome sequencing for 2 individuals. The transcriptome profiles of PN-arrest zygotes were assessed by single-cell RNA sequencing analysis. The variants were then validated by PCR amplification and Sanger sequencing in the affected individuals and other family members. A family characterized by recurrent PN arrest during IVF and ICSI cycles were enrolled after giving written informed consent. Peripheral blood samples were taken for DNA extraction. Three PN-arrest zygotes from patient III-3 were used for single-cell RNA-seq as described. This phenotype was reproduced after multiple cycles of egg retrieval and after trying different fertilization methods and multiple ovulation regimens. The mutant genes of whole exon sequencing were screened and verified. The missense variant c. C1630T (p.R544W) in RGS12 was responsible for a phenotype characterized by paternal transmission. RGS12 controls Ca2+ oscillation, which is required for oocyte activation after fertilization. Single-cell transcriptome profiling of PN-arrest zygotes revealed defective established translation, RNA processing and cell cycle, which explained the failure of complete oocyte activation. Furthermore, we identified proximal genes involved in Ca2+ oscillation-cytostatic factor-anaphase-promoting complex (Ca2+ oscillation-CSF-APC) signaling, including upregulated CaMKII, ORAI1, CDC20, and CDH1 and downregulated EMI1 and BUB3. The findings indicate abnormal spontaneous Ca2+ oscillations leading to oocytes with prolonged low CSF level and high APC level, which resulted in defective nuclear envelope breakdown and DNA replication. We have identified an RGS12 variant as the potential cause of female infertility characterized by arrest at the PN stage during multiple IVF and ICSI.
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INTRODUCTION: Does an elevation in d-Galactose (D-Gal) levels within the body contribute to abnormal embryonic development and placental dysfunction during pregnancy? METHODS: Mouse embryos were cultivated to the blastocyst stage under varying concentrations of D-Gal. The blastocyst formation rate was measured, and the levels of reactive oxygen species (ROS), sirtuin 1 (SIRT1), and forkhead box O3a (FOXO3a) in blastocysts were assessed. Mice were intraperitoneally injected with either saline or D-Gal with or without SRT1720. On the 14th day of pregnancy, the fetal absorption rate and placental weight were recorded. Placental levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were determined. The expression of senescence-related factors, such as senescence-associated ß-galactosidase (SA-ß-gal) in the placenta was examined, and the expression of placental SIRT1, FOXO3a and p21 was evaluated by immunohistochemistry and Western blotting. RESULTS: D-Gal adversely affects early embryonic development in vitro, resulting in a decreased blastocyst formation rate. Furthermore, D-Gal downregulates SIRT1 and FOXO3a while increasing ROS levels in blastocysts. Concurrently, D-Gal induces placental dysfunction, characterized by an elevated fetal absorption rate, reduced placental weight, diminished SOD activity, and increased MDA content. The senescence-related factor SA-ß-gal was detected in the placenta, along with altered expression of placental SIRT1, FOXO3a, and p21. The SIRT1 agonist SRT1720 mitigated this damage by increasing SIRT1 and FOXO3a expression. DISCUSSION: The inhibition of early embryonic development and placental dysfunction induced by D-Gal may be attributed to the dysregulation of SIRT1. Activating SIRT1 emerges as a potentially effective strategy for alleviating the adverse effects of D-Gal exposure.
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Desenvolvimento Embrionário , Proteína Forkhead Box O3 , Galactose , Placenta , Espécies Reativas de Oxigênio , Sirtuína 1 , Animais , Proteína Forkhead Box O3/metabolismo , Feminino , Sirtuína 1/metabolismo , Gravidez , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Desenvolvimento Embrionário/efeitos dos fármacos , Placenta/metabolismo , Placenta/efeitos dos fármacos , Doenças Placentárias/metabolismo , Doenças Placentárias/induzido quimicamenteRESUMO
AIM: miR-141-5p expression in patients with Early Spontaneous Abortion (ESA) and its correlation with hormone levels during pregnancy were investigated. METHODS: A total of 70 pregnant women with ESA were selected as the research group, and 70 normal pregnant women who chose abortion for non-medical reasons were selected as the Con group. Serum ß-HCG, Progesterone (P), and Estrogen (E2) were detected by enzyme-linked immunosorbent assay. Differentially expressed miRNAs were screened by miRNA microarray analysis. miR-141-5p expression was detected by RT-qPCR, and its correlation with serum ß-HCG, P, and E2 levels was analyzed. The diagnostic value of miR-141-5p for ESA was evaluated by the ROC curve. RESULTS: Serum ß-HCG, P, and E2 were decreased and serum miR-141-5p was increased in patients with ESA. Pearson correlation analysis showed that serum ß-HCG, P, and E2 levels were negatively correlated with miR-141-5p expression levels. ROC curve showed that miR-141-5p had a diagnostic value for ESA. CONCLUSIONS: miR-141-5p is related to hormone levels during pregnancy and is expected to become a new candidate diagnostic marker for ESA.
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Aborto Espontâneo , MicroRNAs , Humanos , Feminino , Gravidez , Aborto Espontâneo/diagnóstico , Relevância Clínica , MicroRNAs/genética , Biomarcadores , ProgesteronaRESUMO
Varicocele (VC) is a common cause of infertility in men. Pathophysiological changes caused by VC, such as testicular hypoxia, high temperatures, oxidative stress, abnormal reproductive hormones, and Cd accumulation, can induce autophagy, thus affecting the reproductive function in patients with this condition. Autophagy regulators can be classified as activators or inhibitors. Autophagy activators upregulate autophagy, reduce the damage to the testis and epididymis, inhibit spermatogenic cell apoptosis, and protect fertility. In contrast, autophagy inhibitors block autophagy and aggravate the damage to the reproductive functions. Therefore, elucidating the role of autophagy in the occurrence, development, and regulation of VC may provide additional therapeutic options for men with infertility and VC. In this review, we briefly describe the progress made in autophagy research in the context of VC.
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Autofagia , Varicocele , Autofagia/fisiologia , Varicocele/complicações , Masculino , Humanos , Animais , Infertilidade Masculina/etiologia , TestículoRESUMO
Background: Polycystic Ovary Syndrome (PCOS) is a heritable condition with an as yet unclear etiology. Various factors, such as genetics, lifestyle, environment, inflammation, insulin resistance, hyperandrogenism, iron metabolism, and gut microbiota, have been proposed as potential contributors to PCOS. Nevertheless, a systematic assessment of modifiable risk factors and their causal effects on PCOS is lacking. This study aims to establish a comprehensive profile of modifiable risk factors for PCOS by utilizing a two-sample Mendelian Randomization (MR) framework. Methods: After identifying over 400 modifiable risk factors, we employed a two-sample MR approach, including the Inverse Variance Weighted (IVW) method, Weighted Median method, and MR-Egger, to investigate their causal associations with PCOS. The reliability of our estimates underwent rigorous examination through sensitivity analyses, encompassing Cochran's Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots. Results: We discovered that factors such as smoking per day, smoking initiation, body mass index, basal metabolic rate, waist-to-hip ratio, whole body fat mass, trunk fat mass, overall health rating, docosahexaenoic acid (DHA) (22:6n-3) in blood, monounsaturated fatty acids, other polyunsaturated fatty acids apart from 18:2 in blood, omega-3 fatty acids, ratio of bisallylic groups to double bonds, omega-9 and saturated fatty acids, total lipids in medium VLDL, phospholipids in medium VLDL, phospholipids in very large HDL, triglycerides in very large HDL, the genus Oscillibacter, the genus Alistipes, the genus Ruminiclostridium 9, the class Mollicutes, and the phylum Tenericutes, showed a significant effect on heightening genetic susceptibility of PCOS. In contrast, factors including fasting insulin interaction with body mass index, sex hormone-binding globulin, iron, ferritin, SDF1a, college or university degree, years of schooling, household income, the genus Enterorhabdus, the family Bifidobacteriaceae, the order Bifidobacteriales, the class Actinobacteria, and the phylum Actinobacteria were determined to reduce risk of PCOS. Conclusion: This study innovatively employs the MR method to assess causal relationships between 400 modifiable risk factors and the susceptibility of PCOS risk. It supports causal links between factors like smoking, BMI, and various blood lipid levels and PCOS. These findings offer novel insights into potential strategies for the management and treatment of PCOS.
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Análise da Randomização Mendeliana , Síndrome do Ovário Policístico , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/epidemiologia , Humanos , Feminino , Fatores de Risco , Índice de Massa Corporal , Resistência à InsulinaRESUMO
Phthalate exposure is associated with reproductive health, but the mechanism is unclear. This study used human chorionic trophoblast epithelial cells (HTR8/Svneo cells) and mouse embryos as objects aims to explore the effects of phthalate plasticizers on germ cells and fertility and the possible signalling pathways. In the present study, high concentrations of MEHP for 24 h significantly inhibited the proliferation and viability of HTR8/SVneo cells. Compared with the negative control (NC) group, the MEHP medium and high concentration groups promoted the apoptosis of HTR8/SVneo cells and inhibited the cell cycle, HTR8/SVneo cells were blocked in G1/G0 phase and could not enter S phase, and cell meiosis was inhibited. Western blot experiments showed that there was no difference in the protein expression of wnt inhibitory factor 1 (WIF1) and ß-catenin in HTR8/SVneo cells between the MEHP exposure groups and the NC groups. In vitro embryo culture experiments found that there was no difference in blastocyst formation rate among groups after exposure to DEHP for 2 h. Immunofluorescence showed that the expression of WIF1 decreased in the low concentration group, and there was no difference in the medium and high concentration groups, while the expression of ß-catenin was increased in both the low concentration group and the high concentration group. Our data suggest that exposure to phthalate plasticizers can affect the viability, cell cycle and apoptosis of trophoblast cells, resulting in abnormal expression of the embryonic WIF1/ß-catenin signalling pathway and impaired fertility.
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Trofoblastos , beta Catenina , Gravidez , Feminino , Humanos , Animais , Camundongos , Trofoblastos/metabolismo , beta Catenina/metabolismo , Plastificantes/toxicidade , Plastificantes/metabolismo , Linhagem Celular , Desenvolvimento Embrionário , Movimento CelularRESUMO
D-galactose (D-gal) is a reducing sugar widely distributed in food. In a pregnant animal model exposed to D-gal, D-gal was found to have toxic effects on both the mother and foetus through oxidative stress. However, little is known about the effect of D-gal exposure on the placenta and its underlying mechanism. In this study, we evaluated the effects of D-gal on HTR8/SVneo cells and the mechanisms in vitro. In the present study, the activity of HTR8/SVneo human trophoblasts decreased in a time- and concentration-dependent manner after exposure to D-gal. D-gal resulted in premature senescence of HTR8/SVneo cells, as confirmed by assessing ß-galactosidase (SA-ß-gal) activity and the expression of senescence-related factor p21. We also verified the damage of oxidative stress induced by D-gal by measuring the expression of reactive oxygen species (ROS), sirtuin 1 (SIRT1) and forkhead box O (FOXO) 3a. SRT1720, as a SIRT1 activator, mitigated D-gal-induced oxidative stress and senescence by upregulating SIRT1 and FOXO3a expression and reducing ROS production. Our data suggest that D-gal may induce HTR8/SVneo premature ageing through the SIRT1/FOXO3a/ROS signalling pathway mediated by oxidative stress and that SIRT1 protects cells from this damage.
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Galactose , Sirtuína 1 , Animais , Senescência Celular/fisiologia , Proteína Forkhead Box O3/metabolismo , Galactose/metabolismo , Compostos Heterocíclicos de 4 ou mais Anéis , Humanos , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Sirtuína 1/metabolismo , Trofoblastos/metabolismoRESUMO
Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an activator of the NF-κB transcription factor. NF-κB is involved in a variety of inflammatory, anti-apoptotic, and gene regulatory pathways and was recently found to be over-expressed in esophageal cancer cells. Here we investigated the function of TRAF6 in the esophageal cancer cell line EC109. siRNA targeting TRAF6 was introduced into EC109 cells and TRAF6 mRNA and protein levels were subsequently examined via RT-PCR and western blotting. Rates of apoptosis and cell proliferation were also measured using flow cytometry, ethynyl deoxyuridine (EdU), and CCK-8 (Cell Counting Kit-8) assays. The real-time PCR array was applied to profile the expression of TRAF6 related genes. TRAF6-siRNA reduced TRAF6 mRNA and protein expressions. NF-κB p65 protein expression was decreased in TRAF6-targeting siRNA-transfected cells compared to cells of the negative control. TRAF6-siRNA also significantly inhibited proliferation and enhanced apoptosis of EC109 cells. These studies suggested that TRAF6 was required for NF-κB activation in EC109 cells and it may be a good molecular target for suppressing the survival and proliferation of esophageal cancer cells.
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Apoptose , Proliferação de Células , Regulação para Baixo , Neoplasias Esofágicas/patologia , RNA Interferente Pequeno , Fator 6 Associado a Receptor de TNF/metabolismo , Western Blotting , Linhagem Celular Tumoral , Neoplasias Esofágicas/genética , Humanos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator 6 Associado a Receptor de TNF/genéticaRESUMO
An innovative semidry process has been developed to simultaneously remove NO and SO2 from flue gas. According to the conditions of the flue gas circulating fluidized bed (CFB) system, ferrate(VI) absorbent was prepared and added to humidified water, and the effects of the various influencing factors, such as ferrate(VI) concentration, humidified water pH, inlet flue gas temperature, residence time, molar ratio of Ca/(S+N), and concentrations of SO2 and NO on removal efficiencies of SO2 and NO were studied experimentally. Removal efficiencies of 96.1% for SO2 and 67.2% for NO were obtained, respectively, under the optimal experimental conditions, in which the concentration of ferrate(VI) was 0.03 M, the humidified water pH was 9.32, the inlet flue gas temperature was 130 °C, the residence time was 2.2 s, and the molar ratio of Ca/(S+N) was 1.2. In addition, the reaction mechanism of simultaneous desulfurization and denitrification using ferrate(VI) was proposed.
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Recuperação e Remediação Ambiental/instrumentação , Gases/química , Ferro/química , Óxidos de Nitrogênio/isolamento & purificação , Dióxido de Enxofre/isolamento & purificação , Desnitrificação , Desenho de Equipamento , Concentração de Íons de Hidrogênio , Temperatura , Água/químicaRESUMO
BACKGROUND: LIN28B plays an important role in early embryonic development, but its role in villous trophoblast implantation and differentiation remains unknown. This study aims to verify the role of LIN28B in trophoblastic villous tissue and cells from women with URSA (unexplained recurrent spontaneous abortion) and artificial termination of pregnancy (negative control, NC). METHODS: The LIN28B gene and its protein expression level were detected with real-time quantitative PCR, Western immunoblotting analysis, and immunocytochemistry. The gene was also overexpressed in chorionic villous cell lines (HTR-8/SVneo and BeWo) to examine its effect on trophoblast function. RESULTS: The expression of LIN28B mRNA and protein of URSA villi was lower than that in the NC group. At the cellular level, overexpression of LIN28B enhanced cellular migration, and invasion, and inhibited apoptosis. LIN28B may inhibit apoptosis by promoting Akt phosphorylation and by inhibiting Bad phosphorylation and Bcl-2 expression. In addition, LIN28B inhibited cell fusion and reduced cellular syncytia. CONCLUSIONS: LIN28B can inhibit cell invasion and migration in vitro and promote apoptosis and fusion. The low expression of LIN28B in URSA villous trophoblast cells may be one of the causes of abortion. The role of LIN28B in villous trophoblasts needs further study. LAY SUMMARY: Propagation of offspring is of great significance to the continuation of the human race. However, continuous pregnancy is more difficult for some women, especially women who have multiple miscarriages. One important contributor is the cessation of development caused by genetic factors of the embryo, but there are still many unknown reasons. We investigated the LIN28B gene which is a possible pathogenic factor in the placenta. We collected 25 cases of abortion in the experimental group (unexplained recurrent abortion group) and 25 in the control group (artificial termination of pregnancy group): on average at 7-8 weeks of pregnancy. We tested the function of lin28b in these samples and verified its function in cell lines. LIN28B plays an important role in maintaining early pregnancy by promoting the invasion of villous cells, inhibiting apoptosis and fusion, and the reduction of LIN28B expression may lead to the occurrence of early miscarriage.
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Aborto Habitual , Trofoblastos , Apoptose , Movimento Celular , Feminino , Humanos , Placenta , Gravidez , Proteínas de Ligação a RNARESUMO
BACKGROUND: Ovarian hyperstimulation syndrome (OHSS), a life-threatening complication occurring in stimulated ovarian cycles, arises from treatment with gonadotropin for inducing follicular maturation. OBJECTIVES: The aim of this study was to compare the risk factors between patients with severe OHSS and those without OHSS after in vitro fertilization by intracytoplasmatic sperm injection/embryo transfer (IVF-ICSI/ET). Identifying the associated risk factors may provide guidance for clinicians on how to prevent OHSS. MATERIAL AND METHODS: The retrospective study involved patients who had completed IVF-ICSI/ET cycles. The difference in markers for predicting the occurrence of OHSS between groups was compared. The potential protective and risk factors, as well as the predictive markers, were identified. RESULTS: Patients with OHSS were younger (p = 0.015), had higher basal antral follicle counts (AFC) (p < 0.001) and lower total dosages of gonadotropin (Gn) (p = 0.011). On the day of human chorionic gonadotropin (hCG) administration, significantly higher total numbers of follicles (p < 0.001), serum estradiol (E2) (p < 0.001) and progestrone (Pg) (p = 0.001) levels, numbers of oocytes (p < 0.001) and metaphase II (MII) oocytes (p < 0.001) were also observed in the OHSS group when compared to the non-OHSS group. A univariate regression analysis revealed that age (OR = 0.898, 95% CI = 0.822-0.981) and total dosage of Gn (OR = 0.999, 95% CI = 0.999-1.000) were protective factors, whereas AFC (OR = 1.090, 95% CI = 1.051-1.131) and, on the day of hCG injection, the number of follicles (OR = 1.185, 95% CI = 1.027-1.230), serum E2 (OR = 1.000, 95% CI = 1.000-1.000) and Pg (OR = 2.773, 95% CI = 0.510-3.370) levels, the number of oocytes (OR = 1.254, 95% CI = 0.894-1.472) and MII oocytes (OR = 1.238, 95% CI = 0.747-1.217) were risk factors for OHSS. However, a multivariate regression analysis showed that the total number of follicles (OR = 1.124, 95% CI = 1.027-1.230) was the only predictive factor for the occurrence of OHSS. CONCLUSIONS: The study demonstrated that the follicle count measured on the day of hCG administration was the only predictive factor for the occurrence of OHSS. This provides basic guidance to clinicians on the prevention of the complication when using assisted reproductive technologies (ART).
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Folículo Ovariano , Síndrome de Hiperestimulação Ovariana , China , Gonadotropina Coriônica , Feminino , Fertilização in vitro , Humanos , Modelos Logísticos , Síndrome de Hiperestimulação Ovariana/etiologia , Gravidez , Taxa de Gravidez , Estudos RetrospectivosRESUMO
Abstract Aim miR-141-5p expression in patients with Early Spontaneous Abortion (ESA) and its correlation with hormone levels during pregnancy were investigated. Methods A total of 70 pregnant women with ESA were selected as the research group, and 70 normal pregnant women who chose abortion for non-medical reasons were selected as the Con group. Serum β-HCG, Progesterone (P), and Estrogen (E2) were detected by enzyme-linked immunosorbent assay. Differentially expressed miRNAs were screened by miRNA microarray analysis. miR-141-5p expression was detected by RT-qPCR, and its correlation with serum β-HCG, P, and E2 levels was analyzed. The diagnostic value of miR-141-5p for ESA was evaluated by the ROC curve. Results Serum β-HCG, P, and E2 were decreased and serum miR-141-5p was increased in patients with ESA. Pearson correlation analysis showed that serum β-HCG, P, and E2 levels were negatively correlated with miR-141-5p expression levels. ROC curve showed that miR-141-5p had a diagnostic value for ESA. Conclusions miR-141-5p is related to hormone levels during pregnancy and is expected to become a new candidate diagnostic marker for ESA.
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The aim of this retrospective study was to examine how a low estradiol/follicle (E2/fol) may be related to in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI)-embryo transfer outcomes in polycystic ovary syndrome (PCOS) and non-PCOS patients, respectively. Between 2013 and 2017, 516 IVF/ICSI cycles (146 cycles in PCOS patients and 370 cycles in non-PCOS patients) with a long gonadotrophin releasing hormone receptor agonist protocol-including 338 involved fresh transfer cycles (89 cycles in PCOS patients and 249 cycles in non-PCOS patients)-were conducted. Outcomes were compared between 5 groups of PCOS patients defined by E2/fol (pg/mL) as follows: A, <140; B, 140 to 210; C, 210 to 280; D, 280 to 350; and E, >350. Non-PCOS patients' outcomes are grouped as well. Whether in PCOS or non-PCOS patients, those in the lowest E2/fol group (<140âpg/mL) tended to be younger, and with a greater body mass index (BMI) and antral follicle count (AFC), than the patients in the other groups. Relative to the other groups, Group A showed a lower number and rate of oocytes, higher single pronucleus (1PN) and triple pronucleus (3PN) formation rate, early and advanced abortion rates, but these did not differ significantly from those of the other groups, it perhaps due to the limited sample size. Group A have a higher incidence of moderate or severe ovarian hyperstimulation syndrome than the other groups in non-PCOS patients (Pâ>â.05). Whether in PCOS or non-PCOS patients, greater BMI, greater AFC, and younger age may favor the phenomenon of low E2/fol. In turn, low E2/fol may reduce the oocyte retrieval rate and increase the risk of 1PN and 3PN formation and abortion.
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Estradiol/sangue , Fertilização in vitro/efeitos adversos , Infertilidade Feminina/terapia , Folículo Ovariano , Síndrome do Ovário Policístico/sangue , Adulto , Transferência Embrionária/métodos , Feminino , Fertilização in vitro/métodos , Humanos , Infertilidade Feminina/sangue , Infertilidade Feminina/etiologia , Síndrome de Hiperestimulação Ovariana/epidemiologia , Síndrome de Hiperestimulação Ovariana/etiologia , Indução da Ovulação/efeitos adversos , Síndrome do Ovário Policístico/complicações , Gravidez , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas/efeitos adversos , Injeções de Esperma Intracitoplásmicas/métodos , Resultado do Tratamento , Adulto JovemRESUMO
The association of varicoceles with infertility is well established, but the exact effect of varicoceles on semen quality among patients with infertility is still poorly known. The study aimed to examine the prevalence of varicoceles among Chinese men with infertility and to examine the factors associated with semen quality.This was a cross-sectional study of 5447 male patients treated for infertility at the Affiliated Hospital of Guangdong Medical University from October 2012 to December 2015. The patients were divided on the basis of the presence of varicoceles. Examinations of the amount of semen and sperm morphology were performed according to seminal parameter detection methods recommended by the World Health Organization.Patients with varicoceles (nâ=â1429/5447, 26.2%) were slightly younger (Pâ=â.046), and had smaller testis (Pâ=â.019), higher frequency of abnormal epididymis (Pâ<â.001), slightly shorter infertility duration (Pâ=â.046), and lower frequency of smokers (Pâ=â.012). There was no difference in the distribution of occupations (Pâ=â.777). Using multiple linear regression analysis, varicoceles were shown to be independently associated with semen volume [Bâ=â-0.153, 95% confidence interval (95% CI): -0.245 to -0.062, Pâ=â.001], sperm concentration (Bâ=â9.633, 95% CI: 7.152-12.114, Pâ<â.001), proportion of sperms with normal morphology (Bâ=â0.951, 95% CI: 0.623-1.278, Pâ<â.001), motility (Bâ=â3.835, 95% CI: 2.675, 4.995, Pâ<â.001), total sperm count (Bâ=â22.481, 95% CI: 13.333-31.629, Pâ<â.001), and forward movement sperm count (Bâ=â15.553, 95% CI: 9.777-21.329, Pâ<â.001). Varicoceles were present in 26% of Chinese male patients with infertility.Varicoceles were independently associated with sperm volume, sperm concentration, proportion of sperms with normal morphology, motility, total sperm count, and forward movement sperm count.
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Contagem de Espermatozoides , Motilidade dos Espermatozoides , Varicocele/fisiopatologia , Fatores Etários , China , Estudos Transversais , Humanos , Infertilidade Masculina/patologia , Infertilidade Masculina/fisiopatologia , Infertilidade Masculina/terapia , Modelos Lineares , Masculino , Ocupações , Varicocele/patologia , Varicocele/terapiaRESUMO
Estrogen receptors (ERs) are frequently expressed in human tumor tissues. There have been several studies concerning ER expression in esophageal cancers, yet the results are inconsistent, and the prognostic value of the receptors remains unclear. In the present study, we investigated the expression of ER protein and its correlation with clinical features of esophageal squamous cell carcinoma (ESCC) patients. Immunohistochemical staining for the ERs was carried out on paraffin-embedded primary tumor tissue sections from 89 patients with ESCC. Quantitative analyses were performed to determine the prognostic value of the expression of ERs, and Pearson's correlation was used to examine the relationship between ERα and ERß expression levels. Our results showed that ERα immunoreactivity was significantly lower in ESCC than that in the non-neoplastic epithelium (P=0.0445), whereas the ERß status was much stronger in ESCC than that in the non-neoplastic epithelium (P=0.0243). A significant inverse correlation was observed between ERα expression and depth of tumor invasion (P=0.0426). Correlation analysis revealed a statistically significant inverse correlation between the expression of ERα and ERß in ESCC (r=-0.2902, P=0.0058). Kaplan-Meier survival analysis showed that the patients with ERα expression (21/89) had a better outcome than patients without ERα expression (P=0.0280), whereas patients with high ERß immunoreactivity (44/89) were significantly associated with worse survival (P=0.0366). In conclusion, ERα and ERß levels were inversely correlated, and the downregulation of ERα and upregulation of ERß may indicate unfavorable prognosis of ESCC.
Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Receptor alfa de Estrogênio/biossíntese , Receptor beta de Estrogênio/biossíntese , Idoso , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , PrognósticoRESUMO
BACKGROUND AND OBJECTIVES: Human papillomaviruses have been linked causally to some human cancers such as cervical carcinoma, but there is very little research addressing the effect of HPV infection on human liver cells. We chose the human hepatoma derived cell line Hep G2 to investigate whether HPV gene integration took place in liver cells as well. METHODS: We applied PCR to detect the possible integration of HPV genes in Hep G2 cells. We also investigated the expression of the integrated E6 and E7 genes by using RT-PCR and Western blotting. Then, we silenced E6 and E7 expression and checked the cell proliferation and apoptosis in Hep G2 cells. Furthermore, we analyzed the potential genes involved in cell cycle and apoptosis regulatory pathways. Finally, we used in situ hybridization to detect HPV 16/18 in hepatocellular carcinoma samples. RESULTS: Hep G2 cell line contains integrated HPV 18 DNA, leading to the expression of the E6 and E7 oncogenic proteins. Knockdown of the E7 and E6 genes expression reduced cell proliferation, caused the cell cycle arrest at the S phase, and increased apoptosis. The human cell cycle and apoptosis real-time PCR arrays analysis demonstrated E6 and E7-mediated regulation of some genes such as Cyclin H, UBA1, E2F4, p53, p107, FASLG, NOL3 and CASP14. HPV16/18 was found in only 9% (9/100) of patients with hepatocellular carcinoma. CONCLUSION: Our investigations showed that HPV 18 E6 and E7 genes can be integrated into the Hep G2, and we observed a low prevalence of HPV 16/18 in hepatocellular carcinoma samples. However, the precise risk of HPV as causative agent of hepatocellular carcinoma needs further study.