A5043293616- Effects and risks of endocrine disrupting chemicals
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Sexual Differentiation and Disorders
- Birth, Development, and Health
- Toxic Organic Pollutants Impact
- Sperm and Testicular Function
- Carcinogens and Genotoxicity Assessment
- Reproductive Biology and Fertility
- Per- and polyfluoroalkyl substances research
- Agricultural safety and regulations
- Renal and related cancers
- Urological Disorders and Treatments
- Estrogen and related hormone effects
- Genetically Modified Organisms Research
- Animal Genetics and Reproduction
- Molecular Biology Techniques and Applications
- Thyroid Disorders and Treatments
- Pesticide Exposure and Toxicity
- Animal testing and alternatives
- Adipose Tissue and Metabolism
- Health, Environment, Cognitive Aging
- Chemical Safety and Risk Management
- Testicular diseases and treatments
- Peroxisome Proliferator-Activated Receptors
- Vitamin D Research Studies
Technical University of Denmark
2016-2025
Food Research Institute
2014-2022
Odense University Hospital
2022
University Medical Center Utrecht
2022
Danmarks Nationalbank
2019
The University of Queensland
2008-2018
Copenhagen University Hospital
2014
Rigshospitalet
2014
Griffith University
2002-2006
Institut thématique Génétique, génomique et bioinformatique
2006
MicroRNAs are important regulators of developmental gene expression, but their contribution to fetal gonad development is not well understood. We have identified the evolutionarily conserved gonadal microRNAs miR-202-5p and miR-202-3p as having a potential role in regulating mouse embryonic differentiation. These expressed sexually dimorphic pattern primordial XY differentiates into testis, with strong expression Sertoli cells. In vivo, ectopic pri-miR-202 XX gonads did result molecular...
Parabens comprise a group of preservatives commonly added to cosmetics, lotions, and other consumer products. Butylparaben has estrogenic antiandrogenic properties is known reduce sperm counts in rats following perinatal exposure. Whether butylparaben exposure can affect endocrine sensitive endpoints, however, remains largely unknown. In this study, time-mated Wistar (n = 18) were orally exposed 0, 10, 100, or 500 mg/kg bw/d from gestation day 7 pup 22. Several endocrine-sensitive endpoints...
Genes related to Dmrt1, which encodes a DNA-binding DM domain transcription factor, act as triggers for primary sex determination in broad range of metazoan species. However, this role is fulfilled mammals by Sry, newly evolved gene on the Y chromosome, such that Dmrt1 has become dispensable and instead maintains Sertoli cell phenotype postnatal testes. Here, we report enforced expression XX mouse fetal gonads using Wt1-BAC transgene system sufficient drive testicular differentiation male...
In biological research the analysis of gene expression levels in cells and tissues can be a powerful tool to gain insights into processes. For this, quantitative RT-PCR (RT-qPCR) is popular method that often involve use constitutively expressed endogenous reference (or 'housekeeping') for normalization data. Thus, it essential genes have been verified stably within specific experimental setting. Here, we analysed stability 12 commonly used (Actb, B2m, Gapdh, Hprt, Pgk1, Rn18s, Rpl13a, Rps18,...
Perfluorooctanesulfonic acid (PFOS) is a persistent anthropogenic chemical that can affect the thyroid hormone system in humans and animals. In adults, hormones (THs) are regulated by hypothalamic-pituitary-thyroid (HPT) axis, but also organs such as liver potentially gut microbiota. PFOS other xenobiotics therefore disrupt TH at various locations through different mechanisms. To start addressing this, we exposed adult male rats to 3 mg PFOS/kg/day for 7 days analysed effects on multiple...
Disruptions in the regulatory pathways controlling sex determination and differentiation can cause disorders of development, often compromising reproductive function. Although extensive efforts have been channeled into elucidating mechanisms many aspects sexual differentiation, majority development phenotypes are still unexplained at molecular level. In this study, we analyzed potential involvement Wnt5a show mice that is male-specifically upregulated within testicular interstitial cells...
Sex determination in fetal germ cells depends on a balance between exposure to retinoic acid (RA) and the degradation of RA achieved by testis-specific expression catabolic cytochrome P450 enzyme, CYP26B1. Therefore, identification factors regulating Cyp26b1 gene is an important goal reproductive biology. We used situ hybridization demonstrate that transcription factor genes steroidogenic factor-1 (Sf1) Sry-related HMG box 9 (Sox9) are coexpressed Sertoli cells, whereas Sf1 Leydig mouse...
Summary Migration of chemicals from packaging materials to foods may lead human exposure. Polyfluoroalkyl substances ( PFAS ) can be used in technical mixtures TM s) for use food paper and board, have been detected serum umbilical cord blood. The specific structures the s are often unknown, but polyfluorinated alkyl phosphate esters PAP characterized s, packaging, food. metabolized into fluorotelomer alcohols FTOH perfluoroalkyl carboxylic acids PFCA s). Some endocrine activities,...
Studies report that fetal exposure to paracetamol/acetaminophen by maternal consumption can interfere with male reproductive development. Moreover, recent biomonitoring data widespread presence of paracetamol in German and Danish populations, suggesting via secondary (nonpharmaceutical) sources, such as metabolic conversion from the ubiquitous industrial compound aniline. In this study, we investigated extent which aniline female Intrauterine gavage pregnant dams resulted shortening...
Thyroid hormones are critical for mammalian brain development. Thus, chemicals that can affect thyroid hormone signaling during pregnancy of great concern. Perfluorohexane sulfonate (PFHxS) is a widespread environmental contaminant found in human serum, breastmilk, and other tissues, capable lowering serum thyroxine (T4) rats. Here, we investigated its effects on the system neurodevelopment following maternal exposure from early gestation through lactation (0.05, 5 or 25 mg/kg/day PFHxS),...
The adverse outcome pathway (AOP) framework provides a practical means for organizing scientific knowledge that can be used to infer cause-effect relationships between stressor events and toxicity outcomes in intact organisms. It has reached wide acceptance as tool aid chemical safety assessment regulatory toxicology by supporting systematic way of predicting health based on accumulated mechanistic knowledge. A major challenge broader application the AOP concept toxicology, however, been...
The production of chlorinated paraffins (CPs) has risen in the past two decades due to their versatile industrial applications. Consequently, CPs are now widely detected human food sources, environment, and matrices such as serum, placenta breast milk. This raises concern about prenatal postnatal exposure. While some studies suggest that certain short-chained (SCCPs) may have endocrine disrupting properties, knowledge potential medium- (MCCP) long-chained (LCCPs) remains relativity sparse....
Introduction: Adverse Outcome Pathways (AOPs) can support both testing and assessment of endocrine disruptors (EDs). There is, however, a need for further development the AOP framework to improve its applicability in regulatory context. Here we have inventoried AOP-wiki identify all existing AOPs related mammalian reproductive toxicity arising from disruption estrogen, androgen, steroidogenesis modalities. Core key events (KEs) shared between relevant were also identified aid network (AOPN)...
Developmental defects caused by targeted gene inactivation in mice are commonly subject to strain-specific modifiers that modulate the severity of phenotype. Although several genetic modifier loci have been mapped mice, gene(s) residing at these mostly unidentified, and molecular mechanisms action remain poorly understood. Mutations Sox18 cause a variable phenotype human congenital syndrome hypotrichosis-lymphedema-telangiectasia, Sox18-null varies from essentially normal completely devoid...
In biological research, quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) assays are commonly employed to study mRNA abundance in cells and tissues. This type of assay usually relies on assessing transcript relative constitutively expressed endogenous reference genes. Therefore, it is important that the genes themselves stably or tissues analyzed, independent factors such as age, sex, disease experimental manipulations. Since no gene at same level all times,...
X-linked ATR-X (alpha thalassemia, mental retardation, X-linked) syndrome in males is characterized by facial dysmorphism, alpha thalassemia and urogenital abnormalities, including small testes. It unclear how mutations the chromatin-remodeling protein ATRX cause these highly specific clinical features, since widely expressed during organ development. To investigate mechanisms underlying testicular defects observed syndrome, we generated ScAtrxKO (Sertoli cell Atrx knockout) mice with...
Mycotoxins are fungi-born metabolites that can contaminate foods through mould-infected crops. They a significant food/feed-safety issue across the globe and represent substantial financial burden for world economy. Moreover, with changing climate fungal biota, there is now much discussion about emerging mycotoxins measurable at levels in crops world-wide. Unfortunately, we still know very little bioavailability toxic potentials of many these less characterized mycotoxins, including large...
The test methods that currently exist for the identification of thyroid hormone system-disrupting chemicals are woefully inadequate. There no internationally validated in vitro assays, and can capture consequences diminished or enhanced action on developing brain missing entirely. These gaps put public at risk assessors a difficult position. Decisions about status as system disruptors based inadequate toxicity data. ATHENA project (Assays Thyroid Hormone axis-disrupting chemicals:...