PAEs 暴露抑制线粒体呼吸链复合体酶活性致胚胎质量下降的机制研究

Reproductive toxicology studies have suggested that phthalates and their metabolites can cause reproductive and developmental toxicity such as in jury of germ cell, interference with the endocrine systems, reduction in oocytes and embryos quality. However, the mechanism of the effects of PAEs exposure on oocyte and embryo mitochondrial leading to embryo quality decline is not clear. The project on the basis of a large number of clinical research data and animal experiment were confirmed the effects of PAEs metabolites on the mitochondrial function harm were examined by Real-Time of PCR, confocal microscopy, and multifunctional chemiluminescence, and put forward the scientific hypothesis about the metabolites of PAEs reducing the expression level of mitochondrial respiratory chain complexes I and III, reducing respiratory chain complex I and III enzyme activity, thereby inducing mitochondrial ROS increased, and then change its function leads to a decrease in oocyte and embryo quality. The study may reveal the mechanism of PAEs exposure on the functional damage of oocyte and embryo mitochondria on the basis of “exposure-effects- mechanism” and to provide a solution to reduce the cumulative effect of PAEs exposure on female reproductive damage by improving oocyte and embryo mitochondrial function.

生殖毒理学研究表明酞酸酯类（PAEs）及其代谢产物对雌性动物具有损伤生殖细胞、干扰内分泌系统、降低卵母细胞和胚胎的质量等生殖毒性，但PAEs暴露对卵母细胞和胚胎线粒体的影响导致胚胎质量下降的研究机制尚不清楚。本课题结合前期大量的临床研究数据，在动物预实验的基础上，采用Real-Time PCR、共聚焦显微镜、多功能化学发光仪验证了PAEs代谢产物对胚胎线粒体功能的影响，并提出PAEs代谢产物通过降低线粒体呼吸链复合体I和III的表达水平，降低呼吸链复合体I和III酶的活性，从而诱导线粒体产生ROS增多，进而改变其功能导致卵母细胞和胚胎质量下降的科学假说。在“暴露-效应-机制”的基础上揭示PAEs暴露对卵母细胞和胚胎线粒体功能毒性损伤的研究机制，从改善卵母细胞和胚胎线粒体功能入手阻断PAEs暴露对女性生殖损伤的累积效应提供解决方案。

生殖毒理学研究表明酞酸酯类（PAEs）及其代谢产物对雌性动物具有损伤生殖细胞、干扰内分泌系统、降低卵母细胞和胚胎的质量等生殖毒性，但PAEs暴露对卵母细胞和胚胎线粒体的影响导致胚胎质量下降的研究机制尚不清楚。本课题结合前期大量的临床研究数据，在动物预实验的基础上，采用Real-Time PCR、共聚焦显微镜、多功能化学发光仪验证了PAEs代谢产物对胚胎线粒体功能的影响，并提出PAEs代谢产物通过降低线粒体呼吸链复合体I和III的表达水平，降低呼吸链复合体I和III酶的活性，从而诱导线粒体产生ROS增多，进而改变其功能导致卵母细胞和胚胎质量下降。在“暴露-效应-机制”的基础上揭示PAEs暴露对卵母细胞和胚胎线粒体功能毒性损伤的研究机制，从改善卵母细胞和胚胎线粒体功能入手阻断PAEs暴露对女性生殖损伤的累积效应提供解决方案。面对PAEs的广泛暴露，不孕率和流产率逐年增多，本研究将从分子机制新的层面进一步阐明PAEs暴露对卵母细胞和胚胎线粒体毒性的机制研究，为临床阻断PAEs对女性生殖损害提出有效的解决方案具有重要科学意义，为下一步我们实施不孕女性相关的临床实验奠定了坚实的研究基础。