RESUMEN
Objective@#To explore the effectiveness of the comprehensive intervention on prevention of deciduous primary caries in 3-year-old children, so as so provide reference for the prevention, health care and treatment of oral caries.@*Methods@#Three-year-old children selected by drawing lots from 10 public kindergartens in 5 districts of Bengbu were examined in 2021, and were randomly divided into intervention group ( n =300) and control group ( n =300). During the initial examination, caries loss (dmf) including dental caries, missing teeth, filling teeth were assessed in the two groups. At the initial examination, the intervention group received caries intervention while no intervention was administered in the non-intervention group until half a year later. Intervention measures included education, diet, self-cleaning and fluoride application intervention. The number of cases and the mean of caries loss in the two groups were compared by χ 2 test.@*Results@#Before the intervention, 43 children in the control group suffered from caries, with 88 dmf, including 44 dmf for boys and 44 dmf for girls. There were 45 children in the intervention group, with 101 dmf, including 49 dmf for boys and 52 dmf for girls. There was no significant difference in the number of dmf between the intervention group and the control group ( χ 2=0.91, P >0.05), and there was no significant difference in the prevalence rate (15.0%, 14.3%, χ 2=0.05, P >0.05). After the intervention, there were 26 new dental caries and 43 dmf in intervention group, including 25 dmf for boys and 18 dmf for girls. In the control group, there were 83 new dental caries and 168 dmf, including 72 dmf for boys and 96 dmf for girls. Compared with the control group, the new dmf in the intervention group was significantly different ( χ 2=75.38, P < 0.05). The number of new dental caries patients in the intervention group was significantly different from that in the control group ( χ 2=36.42, P <0.05).@*Conclusion@#Comprehensive interventions to prevent dental caries can significantly reduce the incidence of primary teeth caries in children. It is suggested to intervene dental caries as early as possible to reduce the incidence of dental caries and other oral diseases.
RESUMEN
Embryo implantation is a highly synchronized process between an activated blastocyst and a receptive uterus. Successful implantation relies on the dynamic interplay of estrogen and progesterone, but the key mediators underlying embryo implantation are not fully understood. Here we show that transcription factor early growth response 1 (Egr1) is regulated by estrogen as a downstream target through leukemia inhibitory factor (LIF) signal transducer and activator of transcription 3 (STAT3) pathway in mouse uterus. Egr1 is localized in the subluminal stromal cells surrounding the implanting embryo on day 5 of pregnancy. Estrogen rapidly, markedly, and transiently enhances Egr1 expression in uterine stromal cells, which fails in estrogen receptor α knock-out mouse uteri. STAT3 is phosphorylated by LIF and subsequently recruited on Egr1 promoter to induce its expression. Our results of Egr1 expression under induced decidualization in vivo and in vitro show that Egr1 is rapidly induced after deciduogenic stimulus. Egr1 knockdown can inhibit in vitro decidualization of cultured uterine stromal cells. Chromatin immunoprecipitation data show that Egr1 is recruited to the promoter of wingless-related murine mammary tumor virus integration site 4 (Wnt4). Collectively, our study presents for the first time that estrogen regulates Egr1 expression through LIF-STAT3 signaling pathway in mouse uterus, and Egr1 functions as a critical mediator of stromal cell decidualization by regulating Wnt4.
Asunto(s)
Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Implantación del Embrión , Estrógenos/metabolismo , Factor Inhibidor de Leucemia/metabolismo , Factor de Transcripción STAT3/metabolismo , Proteína Wnt4/metabolismo , Animales , Secuencia de Bases , Inmunoprecipitación de Cromatina , Cartilla de ADN , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Femenino , Técnica del Anticuerpo Fluorescente , Técnicas de Silenciamiento del Gen , Hibridación in Situ , Ratones , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND: Junctional adhesion molecule 2 (Jam2) is a member of the JAM superfamily. JAMs are localized at intercellular contacts and participated in the assembly and maintenance of junctions, and control of cell permeability. Because Jam2 is highly expressed in the luminal epithelium on day 4 of pregnancy, this study was to determine whether Jam2 plays a role in uterine receptivity and blastocyst attachment in mouse uterus. METHODOLOGY/PRINCIPAL FINDINGS: Jam2 is highly expressed in the uterine luminal epithelium on days 3 and 4 of pregnancy. Progesterone induces Jam2 expression in ovariectomized mice, which is blocked by progesterone antagonist RU486. Jam2 expression on day 4 of pregnancy is also inhibited by RU486 treatment. Leukemia inhibitory factor (LIF) up-regulates Jam2 protein in isolated luminal epithelium from day 4 uterus, which is blocked by S3I-201, a cell-permeable inhibitor for Stat3 phosphorylation. Under adhesion assay, recombinant Jam2 protein increases the rate of blastocyst adhesion. Both soluble recombinant Jam2 and Jam3 can reverse this process. CONCLUSION: Jam2 is highly expressed in the luminal epithelium of receptive uterus and up-regulated by progesterone and LIF via tyrosine phosphorylation of Stat3. Jam2 may play a role in the interaction between hatched blastocyst and receptive uterus.
Asunto(s)
Blastocisto/fisiología , Moléculas de Adhesión Celular/fisiología , Factor Inhibidor de Leucemia/farmacología , Progesterona/farmacología , Animales , Blastocisto/citología , Moléculas de Adhesión Celular/análisis , Implantación del Embrión , Epitelio/metabolismo , Femenino , Uniones Intercelulares/metabolismo , Ratones , Mifepristona/farmacología , Embarazo , Útero/metabolismoRESUMEN
Embryo implantation into the maternal uterus is a crucial step for the successful establishment of mammalian pregnancy. Following the attachment of embryo to the uterine luminal epithelium, uterine stromal cells undergo steroid hormone-dependent decidualization, which is characterized by stromal cell proliferation and differentiation. The mechanisms underlying steroid hormone-induced stromal cell proliferation and differentiation during decidualization are still poorly understood. Ribonucleotide reductase, consisting of two subunits (RRM1 and RRM2), is a rate-limiting enzyme in deoxynucleotide production for DNA synthesis and plays an important role in cell proliferation and tumorgenicity. Based on our microarray analysis, Rrm2 expression was significantly higher at implantation sites compared with interimplantation sites in mouse uterus. However, the expression, regulation, and function of RRM2 in mouse uterus during embryo implantation and decidualization are still unknown. Here we show that although both RRM1 and RRM2 expression are markedly induced in mouse uterine stromal cells undergoing decidualization, only RRM2 is regulated by progesterone, a key regulator of decidualization. Further studies showed that the induction of progesterone on RRM2 expression in stromal cells is mediated by the AKT/c-MYC pathway. RRM2 can also be induced by replication stress and DNA damage during decidualization through the ATR/ATM-CHK1-E2F1 pathway. The weight of implantation sites and deciduoma was effectively reduced by specific inhibitors for RRM2. The expression of decidual/trophoblast prolactin-related protein (Dtprp), a reliable marker for decidualization in mice, was significantly reduced in deciduoma and steroid-induced decidual cells after HU treatment. Therefore, RRM2 may be an important effector of progesterone signaling to induce cell proliferation and decidualization in mouse uterus.
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Proliferación Celular/efectos de los fármacos , Daño del ADN , Progesterona/farmacología , Ribonucleósido Difosfato Reductasa/genética , Útero/efectos de los fármacos , Animales , Western Blotting , Células Cultivadas , Decidua/citología , Decidua/efectos de los fármacos , Decidua/metabolismo , Factor de Transcripción E2F1/genética , Factor de Transcripción E2F1/metabolismo , Implantación del Embrión/efectos de los fármacos , Implantación del Embrión/genética , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Hidroxiurea/farmacología , Masculino , Ratones , Ovariectomía , Embarazo , Unión Proteica , Proteínas Proto-Oncogénicas c-myc/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Ribonucleósido Difosfato Reductasa/metabolismo , Ribonucleótido Reductasas/genética , Ribonucleótido Reductasas/metabolismo , Transducción de Señal/efectos de los fármacos , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismo , Factores de Tiempo , Útero/citología , Útero/metabolismoRESUMEN
The establishment of endometrial receptivity is a prerequisite for successful pregnancy, which is controlled by a complex mechanism. MicroRNAs (miRNAs) are small non-coding RNAs that have emerged as important regulators of gene expression. However, the contribution of miRNAs in endometrial receptivity is still unknown. Here we used rhesus monkey as an animal model and compared the endometrial miRNA expression profiles during early-secretory (pre-receptive) phase and mid-secretory (receptive) phase by deep sequencing. A set of differentially expressed miRNAs were identified, 8 of which were selected and validated using quantitative RT-PCR. To facilitate the prediction of their target genes, the 3'-UTRome was also determined using tag sequencing of mRNA 3'-termini. Surprisingly, about 50% of the 10,677 genes expressed in the rhesus monkey endometrium exhibited alternative 3'-UTRs. Of special interest, the progesterone receptor (PGR) gene, which is necessary for endometrial receptivity, processes an ultra long 3'-UTR (~10 kb) along with a short variant (~2.5 kb). Evolutionary analysis showed that the 3'-UTR sequences of PGR are poorly conserved between primates and rodents, suggesting a species-biased miRNA binding pattern. We further demonstrated that PGR is a valid target of miR-96 in rhesus monkey and human but not in rodents, whereas the regulation of PGR by miR-375 is rhesus monkey-specific. Additionally, we found that miR-219-5p regulates PGR expression through a primate-specific long non-coding RNA immediately downstream of the PGR locus. Our study provides new insights into the molecular mechanisms underlying endometrial receptivity and presents intriguing species-specific regulatory roles of miRNAs.
Asunto(s)
Endometrio/metabolismo , Regulación de la Expresión Génica , Receptores de Progesterona/biosíntesis , Regiones no Traducidas 3' , Animales , Secuencia de Bases , Sitios de Unión , Implantación del Embrión , Femenino , Macaca mulatta , Ratones , MicroARNs/metabolismo , Datos de Secuencia Molecular , Embarazo , Preñez , Útero/metabolismoRESUMEN
BACKGROUND: Delayed implantation is a developmental arrest at the blastocyst stage and a good model for embryo implantation. MicroRNAs (miRNAs) have been shown to be involved in mouse embryo implantation through regulating uterine gene expression. This study was to have an integrative analysis on global miRNA and mRNA expression in mouse uterus under delayed implantation and activation through Illumina sequencing. METHODOLOGY/PRINCIPAL FINDINGS: By deep sequencing and analysis, we found that there are 20 miRNAs up-regulated and 42 miRNAs down-regulated at least 1.2 folds, and 268 genes up-regulated and 295 genes down-regulated at least 2 folds under activation compared to delayed implantation, respectively. Many different forms of editing in mature miRNAs are detected. The percentage of editing at positions 4 and 5 of mature miRNAs is significantly higher under delayed implantation than under activation. Although the number of miR-21 reference sequence under activation is slightly lower than that under delayed implantation, the total level of miR-21 under activation is higher than that under delayed implantation. Six novel miRNAs are predicted and confirmed. The target genes of significantly up-regulated miRNAs under activation are significantly enriched. CONCLUSIONS: miRNA and mRNA expression patterns are closely related. The target genes of up-regulated miRNAs are significantly enriched. A high level of editing at positions 4 and 5 of mature miRNAs is detected under delayed implantation than under activation. Our data should be valuable for future study on delayed implantation.