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Abstract：
BACKGROUND: Extensive research has been conducted on embryonic developmental disorders linked to Polycystic Ovary Syndrome (PCOS), a pathological condition that affects 5-10% of women and is characterized by irregularities in the menstrual cycle and infertility. By employing RNA sequencing (RNA-seq), we performed an in-depth investigation of PCOS-related changes in gene expression patterns at the mouse blastocyst stage.
METHODS: The zygotes of female B6D2 mice were obtained and then differentiated into blastocysts in K + Simplex Optimised Medium (KSOM) cultures containing exo-NC (negative control for exosomes) or exo-LIPE-AS1 (a novel exosomal marker of PCOS). Subsequently, blastocysts were collected for RNA-seq. The bioinformatics was performed to analyze and compare the differences of gene expression profile between blastocysts of control and PCOS group.
RESULTS: There were 1150 differentially expressed genes (DEGs) between the two groups of mouse blastocysts; 243 genes were upregulated and 907 downregulated in the blastocysts of the exo-LIPE-AS1 group compared to those of the exo-NC group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the genes involved in amino acid synthesis and glutathione metabolic pathways were down-regulated in exo-LIPE-AS1 group.
CONCLUSIONS: This study has revealed that blastocyst developmental retardation may be associated with the downregulation of amino acid synthesis and glutathione metabolism, which may affect energy metabolism, biosynthesis, cellular osmotic pressure, antioxidant synthesis, ROS clearance or mitochondrial function, and ultimately cause blastocyst cell development abnormalities. Our research offers encouraging data on the mechanisms underlying aberrant embryonic development in patients with PCOS as well as potential treatment strategies.
METHODS: The zygotes of female B6D2 mice were obtained and then differentiated into blastocysts in K + Simplex Optimised Medium (KSOM) cultures containing exo-NC (negative control for exosomes) or exo-LIPE-AS1 (a novel exosomal marker of PCOS). Subsequently, blastocysts were collected for RNA-seq. The bioinformatics was performed to analyze and compare the differences of gene expression profile between blastocysts of control and PCOS group.
RESULTS: There were 1150 differentially expressed genes (DEGs) between the two groups of mouse blastocysts; 243 genes were upregulated and 907 downregulated in the blastocysts of the exo-LIPE-AS1 group compared to those of the exo-NC group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the genes involved in amino acid synthesis and glutathione metabolic pathways were down-regulated in exo-LIPE-AS1 group.
CONCLUSIONS: This study has revealed that blastocyst developmental retardation may be associated with the downregulation of amino acid synthesis and glutathione metabolism, which may affect energy metabolism, biosynthesis, cellular osmotic pressure, antioxidant synthesis, ROS clearance or mitochondrial function, and ultimately cause blastocyst cell development abnormalities. Our research offers encouraging data on the mechanisms underlying aberrant embryonic development in patients with PCOS as well as potential treatment strategies.
摘要：
背景：已经对与多囊卵巢综合征（PCOS）相关的胚胎发育障碍进行了广泛的研究，一种影响5-10％女性的病理状况，其特征是月经周期不规则和不孕症。通过使用RNA测序（RNA-seq），我们对小鼠囊胚期与PCOS相关的基因表达模式变化进行了深入研究.
方法:获得雌性B6D2小鼠的受精卵,然后在含有exo-NC(外泌体的阴性对照)或exo-LIPE-AS1(PCOS的新型外泌体标记)的K+Simplex优化培养基(KSOM)培养物中分化成胚泡。随后，收集胚泡的RNA-seq。采用生物信息学方法分析比较PCOS组和对照组胚泡基因表达谱的差异。
结果：两组小鼠囊胚之间有1150个差异表达基因（DEGs）；与exo-NC组相比，exo-LIPE-AS1组的囊胚中有243个基因上调，907个基因下调。京都基因和基因组百科全书（KEGG）途径分析显示，在exo-LIPE-AS1组中，参与氨基酸合成和谷胱甘肽代谢途径的基因下调。
结论：本研究表明，胚泡发育迟缓可能与氨基酸合成和谷胱甘肽代谢的下调有关。这可能会影响能量代谢，生物合成，细胞渗透压,抗氧化剂合成，ROS清除或线粒体功能，并最终导致胚泡细胞发育异常。我们的研究提供了关于PCOS患者异常胚胎发育机制以及潜在治疗策略的令人鼓舞的数据。
方法:获得雌性B6D2小鼠的受精卵,然后在含有exo-NC(外泌体的阴性对照)或exo-LIPE-AS1(PCOS的新型外泌体标记)的K+Simplex优化培养基(KSOM)培养物中分化成胚泡。随后，收集胚泡的RNA-seq。采用生物信息学方法分析比较PCOS组和对照组胚泡基因表达谱的差异。
结果：两组小鼠囊胚之间有1150个差异表达基因（DEGs）；与exo-NC组相比，exo-LIPE-AS1组的囊胚中有243个基因上调，907个基因下调。京都基因和基因组百科全书（KEGG）途径分析显示，在exo-LIPE-AS1组中，参与氨基酸合成和谷胱甘肽代谢途径的基因下调。
结论：本研究表明，胚泡发育迟缓可能与氨基酸合成和谷胱甘肽代谢的下调有关。这可能会影响能量代谢，生物合成，细胞渗透压,抗氧化剂合成，ROS清除或线粒体功能，并最终导致胚泡细胞发育异常。我们的研究提供了关于PCOS患者异常胚胎发育机制以及潜在治疗策略的令人鼓舞的数据。
