Melatonin protects oocytes from MEHP exposure-induced meiosis defects in porcine
Melatonin protects oocytes from MEHP exposure-induced meiosis defects in porcine
复制标题
褪黑激素保护卵母细胞免受 MEHP 暴露引起的猪减数分裂缺陷的影响
DOI：
10.1093/biolre/iox185
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发表时间：
2018
影响因子：
3.6
通讯作者：
Sun Shao-Chen
中科院分区：
文献类型：
--
作者：
Zhang Yu;Wang Teng;Lan Mei;Zang Xin-Wei;Li Yi-Lun;Cui Xiang-Shun;Kim Nam-Hyung;Sun Shao-Chen
2011年，台湾的食品和饮料产品中被报道非法添加DEHP(增塑剂)，引起了全球对食品安全的极大担忧。DHEP对人和动物有多种毒性作用，如内分泌干扰、心脏毒性、生殖功能和发育缺陷。然而，DEHP对哺乳动物卵母细胞质量的毒性作用仍不清楚。鉴于MEHP是DEHP在体内的活性代谢物，本研究以猪卵母细胞为模型，探讨了MEHP对卵母细胞成熟的影响，并研究了褪黑素对MEHP诱导的减数分裂缺陷的影响。结果表明，暴露于MEHP可显著降低猪卵母细胞极体排出率。进一步研究表明，MEHP暴露后，细胞周期进程、减数分裂纺锤体组织和肌动蛋白组装均受到干扰。此外，DNA和组蛋白甲基化水平也受到影响，表现为5mC和H3K4me2水平的变化。这些结果表明，MEHP影响猪卵母细胞的成熟，而在猪卵母细胞中加入褪黑素可显著改善MEHP所致的减数分裂缺陷。我们进一步试图探讨MEHP对卵母细胞毒性的原因，我们发现MEHP暴露导致氧化应激显著增加，并诱导早期细胞凋亡和自噬增加，而褪黑素可以减少这些。综上所述，我们的结果表明，MEHP暴露导致卵母细胞质量恶化，而补充褪黑素则通过拯救卵母细胞氧化应激介导的细胞凋亡和自噬而改善卵母细胞的成熟。
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.