RESUMEN
BACKGROUND: Poor oral hygiene, generally manifesting as dental caries, gingivitis, or periodontitis, is a common chronic condition among both children and adults worldwide and has been reportedly associated with hypertension and arterial stiffness mainly in adult patients. However, these associations have not been well-studied in children and adults in the general population. Therefore, we conducted this cross-sectional study to clarify the associations between oral hygiene indices and high blood pressure (BP)/hypertension and arterial stiffness as assessed by the cardio-ankle vascular index (CAVI) in children along with their mothers. The association between maternal oral hygiene and high BP in children was also examined based on the hypothesis that maternal awareness of oral hygiene is related to their children's oral hygiene. METHODS: This study was conducted as an Adjunct Study of the Aichi Regional Sub-Cohort of the Japan Environment and Children's Study. Participating children (n = 220, 85-104 months old) and their mothers (n = 217, 29-52 years old) underwent dental/intra-oral examination and BP and CAVI assessment. High BP in children and hypertension in mothers were diagnosed according to corresponding American guidelines. Logistic regression analysis or analysis of covariance was used to examine the associations of poor oral hygiene indices with BP and CAVI. RESULTS: Maternal dental caries ≥1 was associated with their hypertension (adjusted odds ratio [aOR]: 2.72, 95% confidence interval (CI): 1.12-6.61). Maternal dental plaque ≥1/3 was associated with maternal hypertension and children's high BP (aOR, 95% CI: 4.71, 1.33-16.73 and 5.67, 1.22-25.04, respectively). Maximum pocket depth ≥4 mm was associated with children's high BP (aOR: 6.85, 95% CI: 1.24-38.01). No associations were observed between oral hygiene indices and CAVI in children; however, there was a significant association between dental plaque and CAVI in mothers (F = 5.62, p < 0.01). CONCLUSIONS: The small sample size, especially the case number, made it necessary to refrain from drawing unambiguous conclusion. The hypothesis that warrants further investigation based on the present study results is that poor oral hygiene is associated with high BP in children and hypertension and arterial stiffness in mothers, and maternal oral hygiene is associated with high BP in children.
Asunto(s)
Hipertensión , Madres , Higiene Bucal , Rigidez Vascular , Humanos , Femenino , Estudios Transversales , Higiene Bucal/estadística & datos numéricos , Adulto , Masculino , Madres/estadística & datos numéricos , Hipertensión/epidemiología , Persona de Mediana Edad , Niño , Japón/epidemiología , Caries Dental/epidemiología , Caries Dental/etiologíaRESUMEN
Recurrent pregnancy loss (RPL) is a major reproductive health issue with multifactorial causes, affecting 2.6% of all pregnancies worldwide. Nearly half of the RPL cases lack clinically identifiable causes (e.g., antiphospholipid syndrome, uterine anomalies, and parental chromosomal abnormalities), referred to as unexplained RPL (uRPL). Here, we perform a genome-wide association study focusing on uRPL in 1,728 cases and 24,315 female controls of Japanese ancestry. We detect significant associations in the major histocompatibility complex (MHC) region at 6p21 (lead variant=rs9263738; P = 1.4 × 10-10; odds ratio [OR] = 1.51 [95% CI: 1.33-1.72]; risk allele frequency = 0.871). The MHC associations are fine-mapped to the classical HLA alleles, HLA-C*12:02, HLA-B*52:01, and HLA-DRB1*15:02 (P = 1.1 × 10-10, 1.5 × 10-10, and 1.2 × 10-9, respectively), which constitute a population-specific common long-range haplotype with a protective effect (P = 2.8 × 10-10; OR = 0.65 [95% CI: 0.57-0.75]; haplotype frequency=0.108). Genome-wide copy-number variation (CNV) calling demonstrates rare predicted loss-of-function (pLoF) variants of the cadherin-11 gene (CDH11) conferring the risk of uRPL (P = 1.3 × 10-4; OR = 3.29 [95% CI: 1.78-5.76]). Our study highlights the importance of reproductive immunology and rare variants in the uRPL etiology.
Asunto(s)
Aborto Habitual , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Femenino , Aborto Habitual/genética , Embarazo , Frecuencia de los Genes , Cadenas HLA-DRB1/genética , Polimorfismo de Nucleótido Simple , Adulto , Alelos , Estudios de Casos y Controles , Antígenos HLA-C/genética , Complejo Mayor de Histocompatibilidad/genética , Cromosomas Humanos Par 6/genética , Variaciones en el Número de Copia de ADN , Haplotipos , Japón/epidemiología , Antígenos HLA-B/genética , Variación GenéticaRESUMEN
Pregnancy involving intricate tissue transformations governed by the progesterone hormone (P4). P4 signaling via P4 receptors (PRs) is vital for endometrial receptivity, decidualization, myometrial quiescence, and labor initiation. This study explored the role of TCF23 as a downstream target of PR during pregnancy. TCF23 was found to be expressed in female reproductive organs, predominantly in uterine stromal and smooth muscle cells. Tcf23 expression was high during midgestation and was specifically regulated by P4, but not estrogen. The Tcf23 knockout (KO) mouse was generated and analyzed. Female KO mice aged 4-6 months exhibited subfertility, reduced litter size, and defective parturition. Uterine histology revealed disrupted myometrial structure, altered collagen organization, and disarrayed smooth muscle sheets at the conceptus sites of KO mice. RNA-Seq analysis of KO myometrium revealed dysregulation of genes associated with cell adhesion and extracellular matrix organization. TCF23 potentially modulates TCF12 activity to mediate cell-cell adhesion and matrix modulation in smooth muscle cells. Overall, TCF23 deficiency leads to impaired myometrial remodeling, causing parturition delay and fetal demise. This study sheds light on the critical role of TCF23 as a dowstream mediator of PR in uterine remodeling, reflecting the importance of cell-cell communication and matrix dynamics in myometrial activation and parturition.
Asunto(s)
Miometrio , Parto , Animales , Femenino , Ratones , Embarazo , Tamaño de la Camada , Ratones Endogámicos C57BL , Ratones Noqueados , Miocitos del Músculo Liso/metabolismo , Miometrio/metabolismo , Parto/metabolismo , Parto/genética , Parto/fisiología , Progesterona/metabolismo , Receptores de Progesterona/metabolismo , Receptores de Progesterona/genética , Útero/metabolismoRESUMEN
Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins and are important for placenta formation during early pregnancy. Recurrent pregnancy loss (RPL) is associated with abnormalities in endometrial extracellular matrix remodeling. This study aimed to elucidate the roles of MMP2 and MMP9 in RPL pathogenesis. In total, 295 women with a history of RPL and 101 controls were included in this genetic study. Genotype analysis was performed using polymerase chain reaction (PCR) restriction fragment length polymorphisms. For proteolytic analysis, decidua and villi were collected from 10 RPL-miscarried women with normal fetal chromosomes (NC) and 19 women with fetal chromosome aberrations (AC). The expression of MMP2 and MMP9 in the decidua and villi was measured by IHC and ELISA. All samples were collected after obtaining informed consent. There were no statistically significant differences in MMP2-735â¯C/T and MMP9-1562â¯C/T frequencies between women with RPL and the controls. There was no significant difference in MMP2 expression levels in the villi; however, MMP9 expression was significantly higher in normal fetal chromosomes. In the decidua, the expression of MMP2 in the NC group was significantly lower, and MMP9 in the NC group was significantly higher than in the AC group. Although no differences in MMP2-735â¯C/T and MMP9-1562â¯C/T gene polymorphisms were observed in the present study, it is suggested that differences at the protein level are involved in the pathogenesis of RPL since MMP expression is not only regulated by genes but also by local inflammation and various inductive signals.
Asunto(s)
Aborto Habitual , Metaloproteinasa 2 de la Matriz , Metaloproteinasa 9 de la Matriz , Humanos , Femenino , Aborto Habitual/genética , Embarazo , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Adulto , Polimorfismo de Nucleótido Simple , Decidua/patología , Decidua/inmunología , Decidua/metabolismo , Genotipo , Predisposición Genética a la EnfermedadRESUMEN
Twelve years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 5th Revised Edition was published in 2023. The 2023 Guidelines includes 5 additional clinical questions (CQs), which brings the total to 103 CQ (12 on infectious disease, 30 on oncology and benign tumors, 29 on endocrinology and infertility and 32 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.