Melatonin protects oocytes from MEHP exposure-induced meiosis defects in porcine

In 2011, DEHP (plasticizer) was reported to illegally be added in food and beverage products in Taiwan, which caused great concerns about food safety worldwide. DHEP has multiple toxic effects to human and animals such as endocrine disruption, cardiotoxicity, reproductive function, and development defects. However, the toxic effects of DEHP on mammalian oocyte quality are still unclear. Since MEHP is the active metabolite of DEHP in vivo, in this study we used porcine oocyte as model to explore the effects of MEHP on oocyte maturation and we also studied the effects of melatonin administration on MEHP exposure-induced meiosis defects. Our results showed that exposure to MEHP significantly decreased the polar body extrusion rate in porcine oocytes. Further study showed that cell cycle progression, meiotic spindle organization, and actin assembly were all disturbed after MEHP exposure. Moreover, the DNA and histone methylation levels were also affected, showing with altered 5mC and H3K4me2 levels. These results indicated that MEHP affected porcine oocyte maturation, while MEHP exposure-induced meiotic defects were all remarkably ameliorated by the administration of melatonin in porcine oocytes. We further tried to explore the causes of MEHP toxicity on oocytes, and we found that MEHP exposure resulted in significant elevations of oxidative stress and induced early apoptosis as well as elevated autophagy, while melatonin administration could reduce these. Taken together, our results indicated that MEHP exposure induced deterioration of oocyte quality, whereas melatonin supplement showed amelioration on oocyte maturation through its rescue effects on oocyte oxidative stress-mediated apoptosis and autophagy. Summary Sentence Melatonin supplement rescued cell cycle and cytoskeleton defects through ameliorating oxidative stress-mediated apoptosis/autophagy in MEHP-exposed porcine oocytes.