Iprodione and/or chlorpyrifos exposure induced testicular toxicity in adult rats by suppression of steroidogenic genes and SIRT1/TERT/PGC-1α pathway

There is cumulative evidence that iprodione (IPR) fungicide and chlorpyrifos (CPF) insecticide are endocrine disruptors that can evoke reproductive toxicity. Yet, the underlying mechanisms are still unclear. Besides, the outcomes of their co-exposure to male sexual behavior and male fertility are still unknown. The effects of IPR (200 mg/kg b.wt) and CPF (7.45 mg/kg b.wt) single or mutual exposure for 65 days on sexual behavior, sex hormones, testicular enzymes, testis, and accessory sex gland histomorphometric measurements. apoptosis, and oxidative stress biomarkers were investigated. In addition, expression of nuclear receptor subfamily group A (NR5A1), 17 beta-hydroxysteroid dehydrogennsf. (HSD17B3), silent information regulator type-1 (SIRT1), telomerase reverse transcriptase (TERT), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha) genes has been assessed. Our results revealed that the individual or concurrent IPR and CPF exposure significantly disturb the sexual behavior, semen characteristics, testicular enzymes, and male hormones level. Oxidative stress caused by IPR and CPF activates apoptosis by inducing Caspase-3 and reducing Bcl-2. Downregulation of HSD17B3, NR5A1, and SIRT1/TERT/PGC-1 alpha pathway was evident. Of note, most of these disturbances were exaggerated in rats co-exposed to IPR and CPF compared to IPR or CPF alone. Conclusively, our findings verified that IPR and CPF possibly damage the male reproductive system, and concurrent exposure should be avoided.