Melatonin enhances mitochondrial biogenesis and protects against rotenone‐induced mitochondrial deficiency in early porcine embryos

Abstract

Melatonin, a major hormone of the pineal gland, exerts many beneficial effects on mitochondria. Several studies have shown that melatonin can protect against toxin‐induced oocyte quality impairment during maturation. However, there is little information regarding the beneficial effects of melatonin on toxin‐exposed early embryos, and the mechanisms underlying such effects have not been determined. Rotenone, a chemical widely used in agriculture, induces mitochondrial toxicity, therefore, damaging the reproductive system, impairing oocyte maturation, ovulation, and fertilization. We investigated whether melatonin attenuated rotenone exposure‐induced impairment of embryo development by its mitochondrial protection effect. Activated oocytes were randomly assigned to four groups: the control, melatonin treatment, rotenone‐exposed, and “rotenone + melatonin” groups. Treatment with melatonin abrogated rotenone‐induced impairment of embryo development, mitochondrial dysfunction, and ATP deficiency, and significantly decreased oxidative stress and apoptosis. Melatonin also increased SIRT1 and PGC‐1α expression, which promoted mitochondrial biogenesis. SIRT1 knockdown or pharmacological inhibition abolished melatonin's ability to revert rotenone‐induced impairment. Thus, melatonin rescued rotenone‐induced impairment of embryo development by reducing ROS production and promoting mitochondrial biogenesis. This study shows that melatonin rescues toxin‐induced impairment of early porcine embryo development by promoting mitochondrial biogenesis.

Pathological Roles of Mitochondrial Oxidative Stress and Mitochondrial Dynamics in Cardiac Microvascular Ischemia/Reperfusion Injury

“…Under physiological conditions, fusion and fission are balanced, and mitochondrial networks are present. Fusion facilitates distribution of metabolites, proteins, and mtDNA and helps maintain electrical and biochemical connectivity [156][157][158]. However, there is little evidence available to describe the precise role played by mitochondrial fusion in microvascular I/R injury.…”

Melatonin protects mouse testes from palmitic acid‐induced lipotoxicity by attenuating oxidative stress and DNA damage in a SIRT1‐dependent manner

“…25 Interestingly, recent studies have shown that melatonin exerts biological effects via a SIRT1-dependent mechanism in aging, inflammation, and embryo development. [26][27][28] Although evidence linking melatonin to the role of SIRT1 has been reported, only a few of the molecular mechanisms involved have been addressed. It would be interesting to clarify the functional link between SIRT1 and melatonin in response to PA-induced lipotoxicity.…”

“…Similarly, SIRT1 has been shown to deacetylate and inactivate p53 in response to DNA damage 25 . Interestingly, recent studies have shown that melatonin exerts biological effects via a SIRT1‐dependent mechanism in aging, inflammation, and embryo development 26‐28 . Although evidence linking melatonin to the role of SIRT1 has been reported, only a few of the molecular mechanisms involved have been addressed.…”

Sirtuin 3 is required for the protective effect of Resveratrol on Manganese‐induced disruption of mitochondrial biogenesis in primary cultured neurons

“…In addition, our results further demonstrated that mitochondrial dysfunction might be related to the disruption of mitochondrial biogenesis, which involves the synthesis of nuclear‐encoded proteins, and the replication of mitochondrial DNA. PGC‐1α/NRF1/TFAM is currently recognized as the major pathway for regulation of mitochondrial biogenesis (Niu et al, 2020). We found that high‐dose Mn treatment significantly reduced their transcription and expression levels along with an inhibition of mtDNA replication, but that low‐dose Mn treatment increased mitochondrial biogenesis.…”

“…A number of researches reveal that RSV is a potent activator of sirtuin 1 (SIRT1), which exerts important biological effects on mitochondrial biogenesis by regulating SIRT1’s downstream target genes, such as peroxisome proliferator‐activated receptor gamma co‐activator‐1α (PGC‐1α) (Fanibunda et al., 2019; Wang et al., 2019). PGC‐1α is a central regulator of mitochondrial biogenesis, and mitochondrial DNA is activated and up‐regulated by the transcription factors nuclear respiratory factor (NRF 1) and mitochondrial transcription factor A (TFAM) (Niu, Zhou, Nie, Shin, & Cui, 2020). However, it is not known whether the protective role of RSV is further associated with the activation of the SIRT1/PGC‐1α pathway in Mn‐induced mitochondrial damage.…”