A5003423643- Effects and risks of endocrine disrupting chemicals
- Thyroid Disorders and Treatments
- Carcinogens and Genotoxicity Assessment
- Pluripotent Stem Cells Research
- Sperm and Testicular Function
- Sexual Differentiation and Disorders
- Agricultural safety and regulations
- Molecular Biology Techniques and Applications
- Toxic Organic Pollutants Impact
- Renal and related cancers
- Pharmaceutical and Antibiotic Environmental Impacts
- Prenatal Substance Exposure Effects
- Neuroscience of respiration and sleep
- Retinoids in leukemia and cellular processes
- Nuclear Receptors and Signaling
- Birth, Development, and Health
- CRISPR and Genetic Engineering
- Neonatal Health and Biochemistry
- Animal testing and alternatives
- Insect and Pesticide Research
- Pharmacological Effects and Toxicity Studies
- Metabolism and Genetic Disorders
- Animal Genetics and Reproduction
- Genetically Modified Organisms Research
- Reproductive biology and impacts on aquatic species
Bayer (Germany)
2020-2025
Bayer (France)
2015-2019
ExxonMobil (United States)
2013
The Queen's Medical Research Institute
2005-2007
MRC Centre for Reproductive Health
2004-2007
Medical Research Council
2004-2007
Queen's University
2006-2007
University of Edinburgh
2004
Fetal exposure of male rats to di (n-butyl) phthalate (DBP) induces testicular changes remarkably similar dysgenesis syndrome in humans; these include induction focal areas dysgenetic tubules otherwise normal testes. In searching for the fetal origins latter, we used image analysis show that 500 mg/kg DBP [embryonic day (E)13.5–20.5)] caused abnormal aggregation Leydig cells centrally testis. This was not due increase cell number, and size significantly reduced DBP-exposed animals, as were...
Certain phthalates can impair Leydig cell distribution and steroidogenesis in the fetal rat utero, but it is unknown whether similar effects might occur human.Our aim this study was to investigate of di(n-butyl) phthalate (DBP), or its metabolite monobutyl (MBP), on testosterone production aggregation (LCA) testis explants from human, compare results with vivo findings for DBP-exposed rats. We also wanted determine if DBP/MBP affects neonatal male marmoset.Fetal obtained [gestation day...
BackgroundFetal exposure of male rats to di(n-butyl) phthalate (DBP) induces reproductive disorders similar those in human testicular dysgenesis syndrome (TDS), including infertility, cryptorchidism, focal “dysgenetic areas,” and Sertoli cell–only tubules the adult testis. Humans are widely exposed DBP, but at much lower levels than causing adverse effects rats.ObjectivesThe objective this study was evaluate end points affected by DBP action fetal life that relevant TDS, compare their dose...
Cryptorchidism is a common reproductive abnormality, possibly resulting from abnormal hormone production/action by the fetal testis. Insulin-like factor 3 (Insl3) thought to be involved in gubernaculum development and transabdominal testicular descent, but its importance unclear, due partly lack of suitable Insl3 antibodies. We generated (by genetic immunization) validated novel antirat antibody, which we used characterize immunoexpression rat Leydig cells (LCs) life until adulthood...
This study sought to establish whether reduced androgen levels/action in the fetal rat testis induced by di(n-butyl) phthalate (DBP) contributes dysgenetic features, namely Sertoli cell number, occurrence of multinucleated gonocytes (MNG), and Leydig aggregation. Pregnant rats were administered treatments or cotreatments designed manipulate testosterone levels [DBP, propionate (TP)] action [flutamide, 7,12-dimethyl-benz[a]anthracene (DMBA)]. The aforementioned end points analyzed related...
This study investigated effects of in utero exposure [embryonic day (e)13.5-e21.5] to di(n-butyl) phthalate (DBP) on fetal gonocytes and postnatal germ cell (GC) development rats focused changes (delayed development) relevant the postulated origins human carcinoma-in situ cells. DBP treatment resulted both early (e15.5-e17.5) late (e19.5-e21.5) gonocytes. The former involved delayed entry proliferating into quiescence, as indicated by prolongation/overexpression octamer-binding transcription...
Foetal exposure of male rats to di(n-butyl) phthalate (DBP) induces testicular changes similar dysgenesis syndrome in humans, including the formation focal 'dysgenetic areas' within post-natal testes, surrounded by otherwise normal tubules exhibiting complete spermatogenesis. We hypothesize that these dysgenetic areas form when Sertoli (and other) cells are 'trapped' during abnormal large Leydig cell (LC) clusters foetal life and day (d) 4 groups intermingled attempt seminiferous tubules. It...
We undertook transcription profiling of fetal testis RNA on gestational days e15.5, 17.5, and 19.5 in offspring from dams treated daily e12.5 with 500 mg/kg di(n-butyl) phthalate (DBP). At e17.5–19.5, reduced expression genes involved cholesterol uptake/metabolism steroidogenesis was identified DBP-exposed animals, including scavenger receptor B1 (SCARB1), HMGCoA synthase, steroidogenic acute regulatory protein, Cyp11a, Cyp17. Genes encoding inhibin-α, phosphatidylethanolamine-binding...
The European Commission intends to protect vertebrate wildlife populations by regulating plant protection product (PPP) active substances that have endocrine-disrupting properties with a hazard-based approach. In this paper we consider how the Commission's regulation and accompanying guidance can be operationalized ensure technically robust process is used distinguish between adverse population-level effects those for which it demonstrated observed (typically in laboratory) do not translate...
Previous analysis of in utero dibutylphthalate (DBP)-exposed fetal rat testes indicated that DBP's antiandrogenic effects were mediated, part, by indirect inhibition steroidogenic factor 1 (SF1), suggesting peroxisome proliferator–activated receptor alpha (PPARα) might be involved through coactivator (CREB-binding protein [CBP]) sequestration. To test this hypothesis, we have performed chromatin immunoprecipitation (ChIP) microarray to assess the DNA binding PPARα, SF1, CBP, and RNA...
The cardiac embryonic stem cell test (ESTc) is a well-studied non-animal alternative method based on differentiation inhibition as measure for developmental toxicity of tested chemicals. In the ESTc, heterogenic population generated besides cardiomyocytes. Using full biological domain ESTc may improve sensitivity system, possibly broadening range chemicals which effects can be detected in test. order to our knowledge and chemical applicability domains we applied hypothesis-generating...