Curcumin protects porcine granulosa cells and mouse ovary against reproductive toxicity of aflatoxin B1 via PI3K/AKT signaling pathway

Abstract

Aflatoxin B1 (AFB1) is a widespread food contaminant with toxic effects on female reproductive system. This concerns the human public health and the development of the livestock industry. Effective and feasible measures against reproductive toxicity of AFB1 are also unknown. Curcumin has been shown to improve animal production performance and alleviate toxicity of AFB1 in other tissues. The study aimed to reveal the potential mechanism of curcumin in alleviating AFB1 exposure-triggered reproductive toxicity in porcine. Porcine GCs and matured oocytes in vitro and mouse ovary in vivo were cultured as model and then exposed to AFB1 and curcumin. The transcriptomics for porcine GCs was performed. The apoptosis, cell cycle, ROS content and mitochondrial membrane potential level analysis were determined using probe staining and flow cytometry. QRT-PCR and western blotting were analyzed for the genes expression. Oocytes maturation and parthenogenetic activation were performed to evaluate the quality of oocytes. The data showed that AFB1 exposure significantly inhibited porcine GCs viability and exhibited concentration-dependent relationship from 1 to 16 μM. Curcumin supplementation efficiently reversed the inhibition of cell viability. Further analysis indicated that curcumin application alleviated AFB1-exposed porcine GCs and mouse ovary mitochondria dysfunction, oxidative stress, cell cycle arrest, and apoptosis. We found that PI3K/Akt signaling pathway plays a vital role in AFB1-induced porcine GCs toxicity through bioinformatic analysis. The data not only confirmed the correlation of PI3K/Akt signaling pathway and oxidative stress, cell cycle arrest and apoptosis, but also consistent with the results that curcumin supplementation could markedly activate the PI3K/Akt signal inhibited by AFB1. Moreover, curcumin reversed AFB1-impaired cumulus-oocyte complex expansion, oocytes maturation rate, blastocyst rate and formation. Our study demonstrated that curcumin supplementation can protect porcine GCs and mouse ovary from toxicity of AFB1 by targeting the PI3K/AKT signaling pathway and provides a viable treatment approach for AFB1-induced female reproductive toxicity.