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

Abstract

Aflatoxin B1 (AFB1) is a major food and feed contaminant that threaten public health. Previous studies indicate that AFB1 exposure disrupted oocyte maturation. However, an effective and feasible method is unavailable for protecting oocytes against toxicity of AFB1. In the present study, using in vitro matured porcine oocytes and parthenogenetic embryos as model, we confirmed that AFB1 exposure during in vitro oocyte maturation (IVM) significantly impaired both nuclear and cytoplasmic maturation in a dose‐ and time‐dependent manner. The different concentrations of melatonin were also tested for their protective effects on oocytes against the AFB1‐induced toxicity. Our results showed that supplementation of a relative high concentration of melatonin (10−3mol/L) during IVM efficiently reversed the impaired development rate and blastocyst quality, to the levels comparable to those of the control group. Further analysis indicated that melatonin application efficiently alleviated reactive oxygen species accumulation and initiation of apoptosis induced by AFB1 exposure. In addition, disrupted GSH/GPX system, as well as inhibited mitochondrial DNA (mtDNA) replication and mitochondrial biogenesis in AFB1‐treated oocytes, can be notably reversed by melatonin application. Furthermore, cumulus cells may be important in mediating the toxicity of AFB1 to oocytes, and the metabolism of AFB1 in cumulus cells can be depressed by melatonin. To the best of our knowledge, this is the first report to confirm that melatonin application can efficiently protect oocytes from AFB1‐induced toxicity. Our study provides a promising and practical strategy for alleviating or reversing AFB1‐induced female reproductive toxicity in both clinical treatment and domestic reproductive management.

Effect of Melatonin on the In Vitro Maturation of Porcine Oocytes, Development of Parthenogenetically Activated Embryos, and Expression of Genes Related to the Oocyte Developmental Capability

“…Culture media supplemented with melatonin are helpful for improving developmental capability and quality of in vitro fertilized embryos in the porcine [27], and melatonin treatment can improve developmental potential of in vitro PA embryos in pigs [28]. Melatonin treatment could protect in vitro oocytes and PA embryos from toxicity (impaired development rate and blastocyst quality) induced by aflatoxin B1 in the porcine [29]. The MT1 receptor is involved in improving development of in vitro embryo by melatonin treatment in cattle [30].…”

Melatonin Abrogates the Anti-Developmental Effect of the AKT Inhibitor SH6 in Bovine Oocytes and Embryos

“…Melatonin also alleviated the apoptotic effect of mycotoxins (β-zearalenol and HT-2) in bovine ovarian granulosa cells [37]. Moreover, it protected oocytes from the harmful effect of paraquat (a widely used herbicide), aflatoxin B1 and Bisphenol A [34,35,36]. However, the actual mechanisms underlying this function are not fully clarified.…”

“…The higher oxygen concentration under the in vitro maturation environment leads to production of high concentrations of ROS which can have detrimental effects on developing embryos [31]. Moreover, the antioxidant activity of melatonin improved the quality of the inferior oocytes [32] in addition to the protective role against certain cytotoxic compounds during IVM process [33,34,35,36]. Also, melatonin alleviated the meiotic defects in fetal mouse oocytes [33] and reduced the apoptosis and oxidative stress in bovine ovarian granulosa cells [37].…”

Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging

“…Reducing oxidative stress and apoptosis of oocytes and promoting mitochondrial function via melatonin treatment have been shown to improve oocyte maturation, fertilization rate, and rate of blastocyst formation (blastocyst cell count) [51][52][53]. Furthermore, the effect of oxidative stress induced by substances that generate ROS, such as bisphenol A (BPA) and aflatoxin B1 (AFB1), is reduced when melatonin is added to the culture medium [54,55]. This action of melatonin reduces ROS and oxidative stress due to its direct antioxidative actions.…”