Ferroptosis-centered Disease Response Information
General Information of the Disease (ID: DIS00149)
Name |
Testicular injury
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ICD |
ICD-11: NB9Z
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Full List of Target(s) of This Ferroptosis-centered Disease
Heme oxygenase 1 (HMOX1)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Testicular injury [ICD-11: NB9Z] | ||||
Responsed Drug | Diethylhexylphthalate | Investigative | |||
Responsed Regulator | Hypoxia-inducible factor 1-alpha (HIF1A) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
HIF-1 signaling pathway | hsa04066 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | TM3 cells | Normal | Mus musculus | CVCL_4326 | |
TM4 cells | Normal | Mus musculus | CVCL_4327 | ||
In Vivo Model |
Specific pathogen-free (SPF) pregnant C57BL/6 mice were purchased from the Experimental Animal Center of Chongqing Medical University. Under SPF conditions, all mice had free access to food and water. All mice were fed under a 12-hour light/dark cycle at 25 ± 2 , and the relative humidity was 50 ± 5%. Male neonatal mice were selected at postnatal day (PND) 21. Since we aimed to mimic the prepubertal testicular injury induced byDEHPexposure, all male mice were randomly divided into four groups and treated by oral gavage from PND22 to PND35 with corn oil (Aladdin, C116023, China), or DEHP at a dose of 100 mg/kg/day (D100), 250 mg/kg/day (D250), or 500 mg/kg/day (D500).
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Response regulation | Di-(2-ethylhexyl) phthalate (DEHP) exposure led to testicular injury including excessive ROS accumulation. Prepubertal DEHP exposure induces ferroptosis in mouse testes. In particular, MEHP exposure leads to ferroptosis in Leydig and Sertoli cells via the HIF-1/HO-1 signaling pathway. | ||||