Rotenone causes mitochondrial dysfunction and prevents maturation in porcine oocytes

Abstract

Rotenone is a commonly used insecticidal chemical in agriculture and it is an inhibitor of mitochondrial complex Ⅰ. Previous studies have found that rotenone induces the production of reactive oxygen species (ROS) by inhibiting electron transport in the mitochondria of somatic and germ cells. However, there is little precise information on the effects of rotenone exposure in porcine oocytes during in vitro maturation, and the mechanisms underlying these effects have not been determined. The Cumulus-oocyte complexes were supplemented with different concentrations of rotenone to elucidate the effects of rotenone exposure on the meiotic maturation of porcine oocytes during in vitro maturation for about 48 hours. First, we found that the maturation rate and expansion of cumulus cells were significantly reduced in the 3 and 5 μM rotenone-treated groups. Subsequently, the concentration of rotenone was determined to be 3 μM. Also, immunofluorescence, western blotting, and image quantification analyses were performed to test the rotenone exposure on the meiotic maturation, total and mitochondrial ROS, mitochondrial function and biogenesis, mitophagy and apoptosis in porcine oocytes. Further experiments showed that rotenone treatment induced mitochondrial dysfunction and failure of mitochondrial biogenesis by repressing the level of SIRT1 during in vitro maturation of porcine oocytes. In addition, rotenone treatment reduced the ratio of active mitochondria to total mitochondria, increased ROS production, and decreased ATP production. The levels of LC3 and active-caspase 3 were significantly increased by rotenone treatment, indicating that mitochondrial dysfunction induced by rotenone increased mitophagy but eventually led to apoptosis. Collectively, these results suggest that rotenone interferes with porcine oocyte maturation by inhibiting mitochondrial function.

Monoterpenoid Epoxidiol Ameliorates the Pathological Phenotypes of the Rotenone-Induced Parkinson’s Disease Model by Alleviating Mitochondrial Dysfunction

“…A number of studies have shown that rotenone induces cell death along the path of mitochondrial-dependent apoptosis, increasing the number of apoptotic cells [ 25 , 56 , 57 ]. In the present study, the effect of diol and its epoxidized form on the survival of the neuroblastoma cell line SH-SY5Y exposed to rotenone was studied.…”

Rotenone-induced PINK1/Parkin-mediated mitophagy: establishing a silkworm model for Parkinson’s disease potential

“…Park and Koh (2020) and Wang et al (2021) discovered that rotenone treatment significantly enhanced the expression of LC3II and p62 in SH-SY5Y cells. In addition, Heo et al (2022) found increased levels of ubiquitin and LC3 expression in rotenone-exposed porcine oocytes. These findings aligned with our results.…”

Berberine Induces Combined Cell Death in Gastrointestinal Cell Lines

“…Furthermore, inhibition of complex II by malonic acid counteracted the effects of BBR and rotenone, suggesting that the activation of complex II as well as inhibition of complex I is involved in the action of BBR. Rotenone enhances ROS production by complex II [ 21 ], induces mitochondrial depolarization [ 22 ], increases mitophagy [ 23 ], and inhibits mitochondrial Fe 2+ oxidation, which results in cytotoxicity [ 24 ]. These suggest that the mitochondrial effects of BBR, like rotenone, are based on the inhibition of complex I.…”