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Showing 2976 to 3000 of 3164 KERs

ID	Upstream Event	Downstream Event	Creation Date	Last Updated	AOPs

439	413: Reduction, Testosterone synthesis in Leydig cells	446: Reduction of testosterone	Nov 29, 2016	Dec 2, 2016	None
2125	413: Reduction, Testosterone synthesis in Leydig cells	1690: Decrease, circulating testosterone levels	May 11, 2020	May 1, 2024	3 AOPs 18: PPARα activation in utero leading to impaired fertility in males 51: PPARα activation leading to impaired fertility in adult male rodents 64: Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
2923	2139: Reduction, the ratio of E2/11-KT in plasma	221: Reduction, Plasma vitellogenin concentrations	May 22, 2023	May 22, 2023	1 AOP 496: Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）
3393	2139: Reduction, the ratio of E2/11-KT in plasma	2137: Increase, Gonadotropins concentration in plasma	Nov 16, 2024	Nov 16, 2024	1 AOP 496: Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）
337	309: Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development	78: Reduction, Cumulative fecundity and spawning	Nov 29, 2016	Mar 20, 2017	9 AOPs 25: Aromatase inhibition leading to reproductive dysfunction 23: Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish) 30: Estrogen receptor antagonism leading to reproductive dysfunction 122: Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation 123: Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription 310: Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR 496: Androgen receptor agonism leading to reproduction dysfunction （in zebrafish） 540: Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production 549: Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafish
3396	309: Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development	1467: Growth, reduction	Nov 16, 2024	Nov 16, 2024	1 AOP 549: Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafish
315	285: Reduction, Vitellogenin synthesis in liver	221: Reduction, Plasma vitellogenin concentrations	Nov 29, 2016	Mar 20, 2017	7 AOPs 25: Aromatase inhibition leading to reproductive dysfunction 23: Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish) 30: Estrogen receptor antagonism leading to reproductive dysfunction 122: Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation 123: Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription 310: Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR 540: Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production
1081	1040: relaxation, smooth muscle	1042: Proliferation/Clonal Expansion, smooth muscle	Nov 29, 2016	Dec 3, 2016	1 AOP 164: Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse
1564	1426: Release of G Proteins	1427: Opening of GIRK channels	Jun 8, 2017	Jun 8, 2017	2 AOPs 233: Mu Opioid Receptor Agonism leading to Analgesia via K Channel Opening 235: Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via K Channel Opening
1568	1426: Release of G Proteins	1429: Inhibition of Ca Channels	Jun 23, 2017	Jun 23, 2017	2 AOPs 234: Mu Opioid Receptor Agonism leading to Analgesia via Ca Channel Inhibition 236: Serotonin 1A Receptor Agonism leading to Anti-depressant Activity via Ca Channel Inhibition
108	87: Release, Cytokine	149: Increase, Inflammation	Nov 29, 2016	Dec 3, 2016	1 AOP 27: Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)
925	87: Release, Cytokine	907: Infiltration, Inflammatory cytokines	Nov 29, 2016	Dec 3, 2016	None
994	87: Release, Cytokine	901: Infiltration, Inflammatory cells	Nov 29, 2016	Nov 29, 2016	None
1963	87: Release, Cytokine	1497: Recruitment of inflammatory cells	Jul 3, 2019	Jul 3, 2019	2 AOPs 303: Frustrated phagocytosis-induced lung cancer 377: Dysregulated prolonged Toll Like Receptor 9 (TLR9) activation leading to Multi Organ Failure involving Acute Respiratory Distress Syndrome (ARDS)
2454	87: Release, Cytokine	1914: Platelet activation, Increased	Aug 4, 2021	Aug 4, 2021	1 AOP 412: Endothelial cell dysfunction leading to thromboinflammation
2455	87: Release, Cytokine	1915: Neutrophil activation, Increased	Aug 4, 2021	Aug 4, 2021	1 AOP 412: Endothelial cell dysfunction leading to thromboinflammation
3751	87: Release, Cytokine	1263: Necrosis	Mar 25, 2026	Mar 25, 2026	1 AOP 638: Co-exposure to microplastics and cadmium leading to progression from NAFLD to liver tumorigenesis
3752	87: Release, Cytokine	1262: Apoptosis	Mar 25, 2026	Mar 25, 2026	1 AOP 638: Co-exposure to microplastics and cadmium leading to progression from NAFLD to liver tumorigenesis
3753	87: Release, Cytokine	2009: Activation, inflammation pathway	Mar 25, 2026	Mar 25, 2026	1 AOP 638: Co-exposure to microplastics and cadmium leading to progression from NAFLD to liver tumorigenesis
1648	495: Repressed expression of steroidogenic enzymes	413: Reduction, Testosterone synthesis in Leydig cells	Aug 11, 2017	Aug 11, 2017	1 AOP 64: Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility
3615	495: Repressed expression of steroidogenic enzymes	1690: Decrease, circulating testosterone levels	Sep 3, 2025	Sep 3, 2025	1 AOP 595: Emerging OPFRS reproductive outcome pathway
3623	495: Repressed expression of steroidogenic enzymes	3: Reduction, 17beta-estradiol synthesis by ovarian granulosa cells	Sep 3, 2025	Sep 3, 2025	None
2436	1902: Repression of Gbx2 expression	1903: foxi1 expression, increased	Jul 14, 2021	Aug 13, 2021	1 AOP 410: GSK3beta inactivation leading to increased mortality via defects in developing inner ear
433	445: Respiratory distress/arrest	351: Increased Mortality	Nov 29, 2016	Dec 20, 2019	1 AOP 16: Acetylcholinesterase inhibition leading to acute mortality
592	445: Respiratory distress/arrest	590: N/A, hypoxia	Nov 29, 2016	Dec 3, 2016	1 AOP 94: Sodium channel inhibition leading to congenital malformations

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