Melatonin inhibits paraquat‐induced cell death in bovine preimplantation embryos

Abstract

Preimplantation embryos are sensitive to oxidative stress-induced damage that can be caused by reactive oxygen species (ROS) originating from normal embryonic metabolism and/or the external surroundings. Paraquat (PQ), a commonly used pesticide and potent ROS generator, can induce embryotoxicity. The present study aimed to investigate the effects of melatonin on PQ-induced damage during embryonic development in bovine preimplantation embryos. PQ treatment significantly reduced the ability of bovine embryos to develop to the blastocyst stage, and the addition of melatonin markedly reversed the developmental failure caused by PQ (20.9% versus 14.3%). Apoptotic assay showed that melatonin pretreatment did not change the total cell number in blastocysts, but the incidence of apoptotic nuclei and the release of cytochrome c were significantly decreased. Using real-time quantitative polymerase chain reaction analysis, we found that melatonin pre-incubation significantly altered the expression levels of genes associated with redox signaling, particularly by attenuating the transcript level of Txnip and reinforcing the expression of Trx. Furthermore, melatonin pretreatment significantly reduced the expression of the pro-apoptotic caspase-3 and Bax, while the expression of the anti-apoptotic Bcl-2 and XIAP was unaffected. Western blot analysis showed that melatonin protected bovine embryos from PQ-induced damage in a p38-dependent manner, but extracellular signal-regulated kinase (ERK) and c-JUN N-terminal kinase (JNK) did not appear to be involved. Together, these results identify an underlying mechanism by which melatonin enhances the developmental potential of bovine preimplantation embryos under oxidative stress conditions.

Melatonin protects in vitro matured porcine oocytes from toxicity of Aflatoxin B1

“…Our data indicates that a relative high level of melatonin (10 −3 mol/L) significantly reversed the reduction in blastocyst quality caused by AFB1 exposure during oocyte maturation. Similarly, previous studies also proved that melatonin has an essential function in improving embryo quality under normal IVM‐IVF conditions or stressed conditions …”

Liver X Receptor Agonist TO901317 Attenuates Paraquat-Induced Acute Lung Injury through Inhibition of NF-κB and JNK/p38 MAPK Signal Pathways

“…Our results showed that TO901317 treatment significantly inhibited PQ-induced apoptosis. Regarding the apoptotic signal pathway, JNK and p38 MAPK were described as the mediator of PQ-induced apoptosis [8] mainly through promoting Bax expression while suppressing Bcl-2 expression [10]. The increased Bax/Bcl-2 ratio leads to reduction of the mitochondrial transmembrane potential and release of proapoptotic protein from the mitochondria into the cytosol, ultimately resulting in apoptosis [35].…”

“…Activation of mitogen-activated protein kinases (MAPKs) may be involved in the molecular mechanism of PQ-induced apoptosis [8]. MAPKs are protein Ser/Thr kinases that respond to various stressors and regulate cellular responses.…”

Protective effects of melatonin on bovine sperm characteristics and subsequent in vitro embryo development

“…Melatonin provided the most desirable characteristics, given its role as an antioxidant that prevents free radical‐mediated damage (Reiter et al, ). Numerous studies have shown that melatonin and its metabolic derivatives modulate the activity of many pro‐ and anti‐oxidant enzymes, leading to a reduction in oxidative damage to lipids, proteins, and DNA (Manchester et al, ; Pang et al, ). More specifically, melatonin can directly benefit sperm characteristics, including enhanced total motility, progressive motility, and viability rates (Ortiz et al, ; Succu et al, ; Ashrafi et al, ); increased sperm membrane and DNA integrity (Succu et al, ; Ashrafi et al, ); reduced membrane lipid peroxidation (Jang et al, ; Ashrafi et al, ); and modulation of sperm capacitation (Casao et al, ).…”