General Information of the Disease (ID: DIS00149)
Name
Testicular injury
ICD
ICD-11: NB9Z
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.
References
Ref 1 Di-(2-ethylhexyl) phthalate exposure leads to ferroptosis via the HIF-1/HO-1 signaling pathway in mouse testes. J Hazard Mater. 2022 Mar 15;426:127807. doi: 10.1016/j.jhazmat.2021.127807. Epub 2021 Nov 24.