{"id":27,"title":"DART AOPs","purpose":"A collection of Adverse Outcome Pathways (AOPs) relevant to Developmental and Reproductive Toxicity (DART).  \r\nIt was initiated following the ISTNET-DART Workshop held in Basel on 24–25 September 2026.  \r\nThis is a first, evolving collection and is open to discussion, review and further refinement.","creation_strategy":"Candidate AOPs were identified through two complementary routes: a semantic screening of the AOP-Wiki using the expert-defined DART scope, and a reviewed ontology-term-based analysis. The combined candidate set was then provisionally assessed for DART strength.  \r\n\r\nThis collection includes all AOPs classified as C1, meaning that developmental or reproductive biology is considered the principal causal focus of the pathway. No restriction was applied based on OECD status; endorsed, under-review and other AOPs were included equally.","creation_strategy_notes":"Candidate AOPs were identified through two complementary routes: a semantic screening of the AOP-Wiki using the expert-defined DART scope, and a reviewed ontology-term-based analysis. The combined candidate set was then provisionally assessed for DART strength.  \r\n\r\nThis collection includes all AOPs classified as C1, meaning that developmental or reproductive biology is considered the principal causal focus of the pathway. No restriction was applied based on OECD status; endorsed, under-review and other AOPs were included equally.","collection_type":"aop","status":"submitted","creator_id":72,"submitted_at":"2026-10-19T04:30:20.000-04:00","approved_at":null,"rejected_at":null,"contributors":[{"id":72,"name":"Clemens Wittwehr"},{"id":19508,"name":"Lidwina Gerner"}],"item_count":88,"items":[{"id":7,"title":"Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female"},{"id":8,"title":"Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals"},{"id":12,"title":"Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging"},{"id":13,"title":"Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities"},{"id":15,"title":"Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations"},{"id":17,"title":"Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory"},{"id":18,"title":"PPARα activation in utero leading to impaired fertility in males"},{"id":23,"title":"Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)"},{"id":25,"title":"Aromatase inhibition leading to reproductive dysfunction"},{"id":28,"title":"Cyclooxygenase inhibition leading reproductive failure"},{"id":29,"title":"Estrogen receptor agonism leading to reproductive dysfunction"},{"id":30,"title":"Estrogen receptor antagonism leading to reproductive dysfunction"},{"id":42,"title":"Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals"},{"id":43,"title":"Disruption of VEGFR Signaling Leading to Developmental Defects"},{"id":51,"title":"PPARα activation leading to impaired fertility in adult male rodents "},{"id":63,"title":"Cyclooxygenase inhibition leading to reproductive dysfunction"},{"id":64,"title":"Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility"},{"id":65,"title":"XX Inhibition of Sodium Iodide Symporter and Subsequent Adverse Neurodevelopmental Outcomes in Mammals"},{"id":66,"title":"Modulation of Adult Leydig Cell Function Subsequent Glucocorticoid Activation in the Fetal Testis"},{"id":67,"title":"Modulation of Adult Leydig Cell Function Subsequent to Estradiaol Activation in the Fetal Testis"},{"id":68,"title":"Modulation of Adult Leydig Cell Function Subsequent to Alterations in the Fetal Testis Protome"},{"id":73,"title":"Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity"},{"id":74,"title":"Modulation of Adult Leydig Cell Function Subsequent to Hypermethylation in the Fetal Testis"},{"id":94,"title":"Sodium channel inhibition leading to congenital malformations"},{"id":100,"title":"Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of female spawning behavior"},{"id":101,"title":"Cyclooxygenase inhibition leading to reproductive dysfunction via inhibition of pheromone release"},{"id":102,"title":"Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition"},{"id":103,"title":"Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint"},{"id":106,"title":"Chemical binding to tubulin in oocytes leading to aneuploid offspring"},{"id":122,"title":"Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation"},{"id":123,"title":"Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription"},{"id":124,"title":"HMG-CoA reductase inhibition leading to decreased fertility"},{"id":126,"title":"Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation"},{"id":134,"title":"Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals"},{"id":146,"title":"Estrogen Receptor Activation and Female Precocious Puberty"},{"id":152,"title":"Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity "},{"id":153,"title":"Aromatase Inhibition leading to Ovulation Inhibition and Decreased Fertility in Female Rats"},{"id":204,"title":"5-hydroxytryptamine transporter inhibition leading to increased reproductive success and population increase"},{"id":207,"title":"NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans"},{"id":208,"title":"Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) and Transforming growth factor (TGF)-beta pathways activation leading to reproductive failure"},{"id":210,"title":"Activation of c-Jun N-terminal kinase (JNK) and Forkhead box O (FOXO) and reduction of WNT pathways leading to reproductive failure: Integrated multi-OMICS approach for AOP building"},{"id":212,"title":"Histone deacetylase inhibition leading to testicular atrophy"},{"id":218,"title":"Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity"},{"id":219,"title":"Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior"},{"id":271,"title":"Inhibition of thyroid peroxidase leading to impaired fertility in fish"},{"id":288,"title":"Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)"},{"id":289,"title":"Inhibition of 5α-reductase leading to decreased population growth rate via impaired fecundity in female fish"},{"id":300,"title":"Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals"},{"id":305,"title":"5α-reductase inhibition leading to short anogenital distance (AGD) in male (mammalian) offspring"},{"id":306,"title":"Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring"},{"id":307,"title":"Decreased testosterone synthesis leading to short anogenital distance (AGD) in male (mammalian) offspring"},{"id":309,"title":"Luteinizing hormone receptor antagonism leading to reproductive dysfunction"},{"id":310,"title":"Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR"},{"id":345,"title":"Androgen receptor (AR) antagonism leading to decreased fertility in females"},{"id":346,"title":"Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation"},{"id":398,"title":"Decreased ALDH1A (RALDH) activity leading to decreased fertility via disrupted meiotic initiation of fetal oogonia "},{"id":400,"title":"Inhibition of CYP26B1 activity in fetal testis leading to reduced fertility"},{"id":442,"title":"Binding to voltage gate sodium channels during development leads to cognitive impairment"},{"id":444,"title":"Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability"},{"id":458,"title":"AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals"},{"id":459,"title":"AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals"},{"id":465,"title":"Alcohol dehydrogenase leading to reproductive dysfunction"},{"id":476,"title":"Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity"},{"id":477,"title":"Androgen receptor (AR) antagonism leading to hypospadias in male (mammalian) offspring"},{"id":485,"title":"Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition"},{"id":492,"title":"Glutathione conjugation leading to reproductive dysfunction via oxidative stress"},{"id":520,"title":"Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory"},{"id":521,"title":"Essential element imbalance leads to reproductive failure via oxidative stress"},{"id":525,"title":"Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory"},{"id":526,"title":"Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Impaired, Spermatogenesis"},{"id":527,"title":"Decreased, Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) leads to Hypospadias, increased"},{"id":528,"title":"Decreased Insulin-like peptide 3 (INSL3) leads to Malformation, cryptorchidism - maldescended testis"},{"id":533,"title":"Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memory"},{"id":537,"title":"Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liver"},{"id":540,"title":"Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production"},{"id":547,"title":"Androgen receptor agonism leading to long anogenital distance (AGD) in female offspring"},{"id":549,"title":"Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafish"},{"id":566,"title":"Decreased, GnRH pulsatility/release leading to estradiol availability, increased via impaired ovulation"},{"id":570,"title":"Decreased testosterone synthesis leading to hypospadias in male (mammalian) offspring"},{"id":571,"title":"5α-reductase inhibition leading to hypospadias in male (mammalian) offspring"},{"id":581,"title":"Glucocorticoid receptor (GR) activation during development leads to cognitive function (COG) decrease"},{"id":595,"title":"Emerging OPFRS reproductive outcome pathway"},{"id":609,"title":"Activation, estrogen receptor alpha leads to prolonged estrus cycle via decreased kisspeptin release"},{"id":616,"title":"organic UV filter and its Photoproducts reproductive toxicity pathways "},{"id":620,"title":"The Adverse Outcome Pathway to Deposition of Energy Leading to Female Decreased Fertility"},{"id":623,"title":"Activation, estrogen receptor alpha leads to persistent vaginal cornification via increased kisspeptin release"},{"id":639,"title":"Activation, estrogen receptor alpha leads to precocious puberty via increased kisspeptin release"},{"id":640,"title":"Activation, estrogen receptor alpha leads to decreased fertility via prolonged estrus cycle"}]}