Expression of Neuropeptide Y gene in mouse testes during testicular development

Aim:To elucidate the distribution and regulation of Neuropeptide Y(NPY)gene expression in testes under physiologi- cal and pathophysiological conditions,such as testicular development,fasting and experimental cryptorchidism. Methods:In the first experiment,C57BL/6J male mice at the ages of 3 days as well as 2,3,5 and 8 weeks were used. In the second and third experiments,adult C57BL/6J male mice were subjected to fasting for 48 h and experimental cryptorchidism for 72 h.The NPY transcripts were detected by isotopic in situ hybridization histochemistry.Results: The NPY transcripts were exclusively expressed in the interstitial cells regardless of the age groups and experimental conditions.The NPY mRNA levels were found to increase significantly with age(from the neonatal to prepubertal period [P<0.01] and from the prepubetal to postpubertal period [P<0.01]).Food deprivation for 48 h resulted in a significant increase in the NPY mRNA levels in the arcuate nucleus of the hypothalamus(P<0.01),but not in the testes.Experimental cryptorchidism for 72 h failed to regulate the NPY gene expression in the testes.Conclusion: NPY gene expression is distributed in Leydig cells and increases in line with testicular development.The regulation of testicular NPY is different from that of hypothalamic NPY.(Asian J Androl 2006 Jul;8:443-449)

X-box binding protein 1 caused an imbalance in pyroptosis and mitophagy in immature rats with di-(2-ethylhexyl)phthalate-induced testis toxicity

As a widely used plasticizer,di-(2-ethylhexyl)phthalate(DEHP)is known to induce significant testicular injury.However,the potential mechanism and effects of pubertal exposure to DEHP on testis development remain unclear.In vivo,postnatal day(PND)21 male rats were gavaged with 0,250,and 500 mg/kg DEHP for ten days.Damage to the seminiferous epithelium and disturbed spermatogenesis were observed after DEHP exposure.Meanwhile,oxidative stress-induced injury and pyroptosis were activated.Both endoplasmic reticulum(ER)stress and mitophagy were involved in this process.Monoethylhexyl phthalate(MEHP)was used as the biometabolite of DEHP in vitro.The GC-1 and GC-2 cell lines were exposed to 0,100μM,200μM,and 400μM MEHP for 24 h.Reactive oxygen species(ROS)generation,oxidative stress damage,ER stress,mitophagy,and pyroptosis were significantly increased after MEHP exposure.The ultrastructure of the ER and mitochondria was destroyed.X-box binding protein 1(XBP1)was observed to be activated and translocated into the nucleus.ROS generation was inhibited by acetylcysteine.The levels of antioxidative stress,ER stress,mitophagy,and pyroptosis were decreased as well.After the administration of the ER stress inhibitor 4-phenyl-butyric acid,both mitophagy and pyroptosis were inhibited.Toyocamycin-induced XBP1 down-regulation decreased the levels of mitophagy and pyroptosis.The equilibrium between pyroptosis and mitophagy was disturbed by XBP1 accumulation.In summary,our findings confirmed that DEHP induced a ROS-mediated imbalance in pyroptosis and mitophagy in immature rat testes via XBP1.Moreover,XBP1 might be the key target in DEHP-related testis dysfunction.