During development, tooth germs undergo various morphological changes resulting from interactions between the oral epithelium and ectomesenchyme. These processes are influenced by the extracellular matrix, the composition of which, along with cell adhesion and signaling, is regulated by metalloproteinases. Notably, these include matrix metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs), and a disintegrin and metalloproteinases with thrombospondin motifs (ADAMTSs). Our analysis of previously published scRNAseq datasets highlight that these metalloproteinases show dynamic expression patterns during tooth development, with expression in a wide range of cell types, suggesting multiple roles in tooth morphogenesis. To investigate this, Marimastat, a broad-spectrum inhibitor of MMPs, ADAMs, and ADAMTSs, was applied to ex vivo cultures of mouse molar tooth germs. The treated samples exhibited significant changes in tooth germ size and morphology, including an overall reduction in size and an inversion of the typical bell shape. The cervical loop failed to extend, and the central area of the inner enamel epithelium protruded. Marimastat treatment also disrupted proliferation, cell polarization, and organization compared with control tooth germs. In addition, a decrease in laminin expression was observed, leading to a disruption in continuity of the basement membrane at the epithelial-mesenchymal junction. Elevated hypoxia-inducible factor 1-alpha gene (Hif-1α) expression correlated with a disruption to blood vessel development around the tooth germs. These results reveal the crucial role of metalloproteinases in tooth growth, shape, cervical loop elongation, and the regulation of blood vessel formation during prenatal tooth development.NEW & NOTEWORTHY Inhibition of metalloproteinases during tooth development had a wide-ranging impact on molar growth affecting proliferation, cell migration, and vascularization, highlighting the diverse role of these proteins in controlling development.
- MeSH
- Hypoxia-Inducible Factor 1, alpha Subunit metabolism genetics MeSH
- Matrix Metalloproteinase Inhibitors pharmacology MeSH
- Hydroxamic Acids pharmacology MeSH
- Metalloproteases metabolism genetics MeSH
- Molar embryology growth & development metabolism enzymology MeSH
- Morphogenesis MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Odontogenesis * MeSH
- Cell Proliferation * MeSH
- Gene Expression Regulation, Developmental MeSH
- Tooth Germ embryology metabolism enzymology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: The objective of this study was to assess the relationship between longitudinal changes in the uterine Doppler velocimetry and the maternal profile of angiogenic factors in the third trimester and to assess their ability to predict term preeclampsia (PE). METHODS: A cohort of low-risk pregnant women was scheduled for a uterine Doppler evaluation and measurement of the circulating levels of angiogenic factors at ∼30 and ∼36 weeks. The performance of both parameters and their change over time in predicting term PE was evaluated. RESULTS: A total of 1,191 women were analyzed, of which 28 (2.4%) women developed term PE. At ∼30 weeks, a model including the sFlt-1/PlGF (fms-like tyrosine kinase-1/placental growth factor) ratio and the uterine Doppler explained 16.2% of the uncertainty of developing term PE, while at ∼36 weeks, the same variables explained 25.2% [p < 0.001]. The longitudinal changes of both predictors had an R2 of 26.8%, which was not different from that of the ∼36 weeks evaluation [p = 0.45]. The area under the curve (AUC) of the ∼36 weeks ratio was significantly higher than at ∼30 weeks (0.86 [0.77-0.94] vs. 0.81 [0.73-0.9]; p = 0.043). The AUC of the longitudinal change of the ratio (0.85 [0.77-0.94]) did not differ from that of at ∼36 weeks (p = 0.82). At ∼36 weeks, for a 10% of false positives, the ratio had a detection rate of 71.4%. CONCLUSION: A cross-sectional measurement of the sFlt-1/PlGF ratio outperforms uterine Doppler in predicting term PE. The combination of both markers does not improve such prediction, nor the evaluation of the longitudinal changes between weeks.
- MeSH
- Adult MeSH
- Humans MeSH
- Placental Circulation physiology MeSH
- Placenta Growth Factor * blood MeSH
- Area Under Curve MeSH
- Predictive Value of Tests MeSH
- Pre-Eclampsia * blood diagnostic imaging MeSH
- Vascular Endothelial Growth Factor Receptor-1 * blood MeSH
- Rheology * methods statistics & numerical data MeSH
- Reproducibility of Results MeSH
- Blood Flow Velocity physiology MeSH
- Pregnancy MeSH
- Pregnancy Trimester, Third * blood physiology MeSH
- Ultrasonography, Doppler methods statistics & numerical data MeSH
- Ultrasonography, Prenatal * methods statistics & numerical data MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
OBJECTIVES: This study aims to explore the lasting effects of stress experienced by pregnant women during World War II (WWII) on body and head measurements of their adult daughters. METHODS: The research sample consists of 336 female university students born in Poland between 1925 and 1951. The data include body measurements and socioeconomic information (parental occupation and number of siblings) acquired from questionnaires collected between the 1950s and 1970s. Student's t-test, Mann-Whitney test and Analysis of Variance were used to analyze differences in body measurements between groups of women born before and during the war, as well as the possible influences of socioeconomic variables. RESULTS: The mean measurements of body height, symphysion height, and waist circumference were lower in women conceived and born during the war compared to those born in the pre-war period. In contrast, the mean measurements of biacromial (shoulder) width, trunk length, and three head dimensions were higher in women conceived and born during the war. Additionally, the number of siblings appeared to be a significant factor that may have influenced the body measurements of women in both groups. For instance, a higher number of living siblings, particularly sisters, was associated with reduced body dimensions, such as body height and waist circumference, while a greater number of deceased siblings was linked to an increase in certain body dimensions. CONCLUSION: The results suggest that war-related prenatal conditions may have influenced the postnatal growth and development of women conceived and born during the war. Notably, the direction of these changes varied, which indicates that the growth response to the war-related conditions was a complex adaptation, reflecting both positive and negative changes in different body parts, rather than a uniform pattern of growth suppression.
- MeSH
- World War II * MeSH
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Stress, Psychological MeSH
- Socioeconomic Factors MeSH
- Pregnancy MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Poland MeSH
INTRODUCTION: This study aimed to validate the Sargent risk stratification algorithm for the prediction of placenta accreta spectrum (PAS) severity using data collected from multiple centers and using the multicenter data to improve the model. MATERIAL AND METHODS: We conducted a multicenter analysis using data collected for the IS-PAS database. The Sargent model's effectiveness in distinguishing between abnormally adherent placenta (FIGO grade 1) and abnormally invasive placenta (FIGO grades 2 and 3) was evaluated. A new model was developed using multicenter data from the IS-PAS database. RESULTS: The database included 315 cases of suspected PAS, of which 226 had fully documented standardized ultrasound signs. The final diagnosis was normal placentation in 5, abnormally adherent placenta/FIGO grade 1 in 43, and abnormally invasive placenta/FIGO grades 2 and 3 in 178. The external validation of the Sargent model revealed moderate predictive accuracy in a multicenter setting (C-index 0.68), compared to its higher accuracy in a single-center context (C-index 0.90). The newly developed model achieved a C-index of 0.74. CONCLUSIONS: The study underscores the difficulty in developing universally applicable PAS prediction models. While models like that of Sargent et al. show promise, their reproducibility varies across settings, likely due to the interpretation of the ultrasound signs. The findings support the need for updating the current ultrasound descriptors and for the development of any new predictive models to use data collected by different operators in multiple clinical settings.
- MeSH
- Algorithms MeSH
- Adult MeSH
- Risk Assessment MeSH
- Humans MeSH
- Placenta Accreta * diagnostic imaging MeSH
- Predictive Value of Tests MeSH
- Prospective Studies MeSH
- Reproducibility of Results MeSH
- Severity of Illness Index MeSH
- Pregnancy MeSH
- Ultrasonography, Prenatal * MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Validation Study MeSH
Gastroschíza je vrozená rozštěpová vada břišní stěny charakterizovaná eventerací střevních kliček obvykle pravostranným paraumbilikálním defektem. Prenatální detekce gastroschízy není díky pokročilým ultrazvukovým metodám obtížná. Časný záchyt vady je klíčový pro optimalizaci prenatální péče i následný management. Prognóza této vady je dobrá a dlouhodobý stav dětí je příznivý, nicméně 10–15 % případů má komplikovaný průběh s vysokým rizikem neonatální mortality či závažné morbidity. Časný záchyt umožňuje efektivní monitorování vývoje plodu, posouzení rizika rozvoje komplikací a jejich minimalizace plánováním porodu v perinatologickém centru s dostupností intenzivní neonatologické péče a možností okamžité chirurgické intervence.
Gastroschisis is a congenital abdominal wall defect characterized by the eventration of bowel loops through a right-sided paraumbilical opening. Prenatal detection of gastroschisis is generally straightforward due to advanced ultrasound techniques, and it is essential for optimizing both prenatal care and subsequent management. The prognosis for this condition is generally favorable, with positive long-term outcomes for most children. However, 10–15% of cases may follow a complicated course with an elevated risk of neonatal mortality or significant morbidity. Early detection enables effective monitoring of fetal development, risk assessment for potential complications, and risk minimization by planning childbirth at a tertiary center equipped with intensive neonatal care and the possibility of prompt surgical intervention.
- MeSH
- Abdominal Wall abnormalities MeSH
- Gastroschisis * diagnostic imaging therapy MeSH
- Humans MeSH
- Infant, Newborn, Diseases MeSH
- Perinatal Care MeSH
- Prenatal Diagnosis methods MeSH
- Prognosis MeSH
- Hernia, Umbilical diagnostic imaging MeSH
- Pregnancy MeSH
- Ultrasonography, Prenatal methods MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- MeSH
- Autoimmunity immunology MeSH
- Embryonic and Fetal Development immunology MeSH
- Fertility immunology MeSH
- Immune System * physiology immunology physiopathology MeSH
- Infertility diagnosis immunology MeSH
- Humans MeSH
- Pre-Eclampsia diagnosis immunology MeSH
- Reproduction * physiology immunology MeSH
- Pregnancy immunology MeSH
- Pregnant People MeSH
- Check Tag
- Humans MeSH
- Pregnancy immunology MeSH
- Female MeSH
- Publication type
- Review MeSH
BACKGROUND: Maternal alcohol consumption can adversely affect children's development, but the impact of paternal drinking is less understood. We aimed to investigate whether maternal or paternal alcohol consumption during pregnancy affected children's mental health and behavior. METHODS: A total of 2,013 parent-child triads from the European Longitudinal Study of Pregnancy and Childhood cohort were used. Data on alcohol consumption was obtained from questionnaires during pregnancy and after the child's birth. Mental health and behavior of children were assessed with Strength and Difficulties Questionnaire (SDQ). The associations were tested using linear regression, adjusting for socio-demographic and psychosocial covariates. RESULTS: Increased maternal alcohol consumption was associated with higher total SDQ scores at ages 7, 11, and 18 years old when the outcomes were reported by mothers, but only at 11 years when reported by children. We did not observe any dose-response relationship, and the effect size did not change during the follow-up. The effects were observed across various domains of SDQ: in the emotional symptoms subscale at age 11, in the conduct problems subscale at ages 7 and 11, and in the hyperactivity/inattention subscale at age 18. Paternal alcohol consumption was not associated with SDQ. CONCLUSIONS: Maternal alcohol consumption during pregnancy is associated with long-term effects on children's mental health and behavior, particularly when reported by mothers. No association was found between paternal alcohol consumption, suggesting that the results may stem from biological effects of alcohol or other factors beyond the direct exposure, potentially encompassing broader maternal psychosocial or behavioral characteristics.
- MeSH
- Child Behavior * MeSH
- Child MeSH
- Adult MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- Mothers * statistics & numerical data MeSH
- Adolescent MeSH
- Fathers * statistics & numerical data MeSH
- Alcohol Drinking * adverse effects epidemiology MeSH
- Pregnancy MeSH
- Prenatal Exposure Delayed Effects * epidemiology MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
BACKGROUND: During human foetal development, the liver is the primary site of blood cell production, but this activity declines in the third trimester and postnatally as haematopoiesis shifts to bone marrow. In humans, this postnatal decline is not well characterized due to the scarcity of appropriate samples. OBJECTIVE: To characterize the effect of (i) gestational age at birth and (ii) length of survival after birth on hepatic haematopoiesis across various cell lineages involved. METHODS: Liver autopsy samples from 25 born-alive infants, predominantly extremely preterm newborns who died mainly between 1 day and 3 weeks after birth, were analysed. Haematopoiesis was characterized using immunohistochemical staining of established cell type-specific protein markers. RNA-sequencing data from our previous study using the same samples were also explored. RESULTS: Haematopoiesis negatively correlates with both the duration of prenatal development and the length of postnatal survival. The effect of these two factors varies across different haematopoietic cell lineages. Prenatally and early postnatally, erythropoietic cells dominated hepatic haematopoiesis but were rapidly suppressed within three days after birth. Granulopoietic activity declined more gradually after birth. Analysis of the gene expression data revealed the possible involvement of several transcription factors in lineage-specific regulatory mechanisms. CONCLUSION: This study enhances our understanding of the postnatal decline of hepatic haematopoiesis in human newborns, highlighting the differential regulation of erythropoiesis and granulopoiesis after birth. These factors bring new in-depth knowledge about the biological processes critical for postnatal adaptation of human newborns.
- Publication type
- Journal Article MeSH
INTRODUCTION: Sacrococcygeal teratoma (SCT) is the most common congenital tumor. The incidence of malignant types is rare but increases with late detection or in case of relapse. Prenatal diagnosis is based on ultrasound examination and magnetic resonance imaging (MRI). Since this is a rare congenital anomaly, we should report all cases to improve prenatal diagnosis and postnatal management. MATERIAL AND METHODS: Retrospective analysis of sixteen cases of sacrococcygeal teratoma delivered and treated at the University Hospital Brno between 2005 and 2020. The following criteria were evaluated: gestational week of the primary diagnosis, exact description of ultrasound findings, pregnancy management, delivery mode, correlation of prenatal ultrasound with postnatal findings in the newborn, as well as the occurrence of early and late complications in newborns and children. RESULTS: Out of sixteen cases, seven cases (43.8%) were indicated for pregnancy termination based on ultrasound findings, the parent's decision, and an estimation of an adverse pregnancy outcome. In nine cases (56.2%), the pregnancy continued and was ended by delivery. In one case, there was an early postnatal death of a newborn after birth in the 25th week of gestation. In eight cases, live fetuses were born in which the tumor was surgically removed between day 1 and 14 months after birth. There was a strong correlation between the tumor description made by prenatal ultrasound diagnosis and related severe complications in newborns. The incidence of severe early and late complications in ongoing pregnancies was very low-only one case of infection in the surgical wound requiring reoperation (12.5%) was described. In two patients (25%), a transient stoma establishment was necessary for secondary ileus. One case of recurrence of the disease at two years of age occurred, requiring the administration of chemotherapy (12.5%), and one patient has mild persistent urinary incontinence. CONCLUSION: Sacrococcygeal teratoma is one of the rarest congenital malformations. A detailed prenatal ultrasound examination is essential to estimate the pregnancy prognosis. The most predictive ultrasound predictor of favorable early and late postnatal outcomes and long-term child development is the presence of cystic sacrococcygeal formation, the most common tumor type, and the absence of signs of cardiac failure due to fetal anemia. In these cases, with early surgical treatment provided, the incidence of severe complications and long-term consequences in children is very low, and parents should be informed during prenatal counseling. It is necessary to register all the SCT cases due to the rarity of this congenital anomaly for further statistical analysis of the importance of ultrasound markers.
- MeSH
- Adult MeSH
- Gestational Age MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Infant, Newborn MeSH
- Prognosis MeSH
- Retrospective Studies MeSH
- Sacrococcygeal Region * diagnostic imaging MeSH
- Pregnancy MeSH
- Teratoma * diagnostic imaging surgery congenital MeSH
- Ultrasonography, Prenatal * MeSH
- Pregnancy Outcome MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
