State Key Laboratory of Animal Nutrition, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China.
J Pineal Res. 2013 Oct;55(3):267-74. doi: 10.1111/jpi.12069. Epub 2013 Jun 15.
When a defect occurs in the in vitro development of a pronuclear embryo, the interruption of the subsequent implantation limits the success of assisted conception. This common problem remains to be solved. In this study, we observed that melatonin at its physiological concentration (10(-7) m) significantly promoted the in vitro development of murine pronuclear embryos. This was indicated by the increased blastocyst rate, hatching blastocyst rate, and blastocyst cell number with melatonin treatment. In addition, when these blastocysts were implanted into female recipient mice, the pregnancy rates (95.0% versus control 67.8%), litter sizes (4.1 pups/litter versus control 2.7 pups/litter), and postnatal survival rates of offspring (96.84% versus control 81.24%) were significantly improved compared with their non-melatonin-treated counterparts. Mechanistic studies revealed that melatonin treatment upregulates gene expression of the antioxidant enzyme, superoxide dismutase (SOD), and the anti-apoptotic factor bcl-2 while downregulating the expression of pro-apoptotic genes p53 and caspase-3. Due to these changes, melatonin treatment reduces ROS production and cellular apoptosis during in vitro embryo development and improves the quality of blastocysts. The implantation of blastocysts with higher quality leads to more healthy offspring and increased pup survival.
当体外培养的原核胚胎出现缺陷时，随后的着床中断会限制辅助受孕的成功。这个常见的问题仍然有待解决。在这项研究中，我们观察到褪黑素在其生理浓度（10(-7) m）下显著促进了鼠原核胚胎的体外发育。这表现为在褪黑素处理下囊胚率、孵化囊胚率和囊胚细胞数量增加。此外，当这些囊胚被植入雌性受体小鼠时，与未用褪黑素处理的囊胚相比，妊娠率（95.0% 对对照 67.8%）、产仔数（4.1 只/窝对对照 2.7 只/窝）和后代的产后存活率（96.84% 对对照 81.24%）显著提高。机制研究表明，褪黑素处理上调了抗氧化酶超氧化物歧化酶（SOD）和抗凋亡因子 bcl-2 的基因表达，同时下调了促凋亡基因 p53 和 caspase-3 的表达。由于这些变化，褪黑素处理减少了体外胚胎发育过程中的 ROS 产生和细胞凋亡，提高了囊胚的质量。质量更高的囊胚的植入导致更健康的后代和更高的幼仔存活率。
