【作者】 张冉；

【导师】 胡亮；

【作者基本信息】 中南大学 ， 遗传学， 2022， 硕士

【摘要】 对于人类生殖来说,发育完全的卵母细胞必不可少。位于卵丘-卵母细胞复合体(COC)中心的卵母细胞成熟是一个被精细调控的复杂过程,它不仅依赖于卵母细胞本身,还依赖于卵母细胞与周围的卵丘颗粒细胞(CCs)之间的相互交流。然而,在卵母细胞成熟这一生理过程中,卵母细胞和CCs的转录组学特征及意义仍不清楚。在这项研究中,我们对47名行胚胎植入前染色体非整倍体检测(PGT-A)患者的卵母细胞及其CCs进行了微量转录组分析,以探讨不同成熟阶段的卵母细胞(GV、MI和MII)和相应CCs在转录组上的关联。我们发现卵母细胞的成熟是一个动态变化的过程,MI阶段卵母细胞可进一步细分为早期MI卵母细胞和晚期MI卵母细胞。GV卵母细胞能量消耗比较旺盛,由于此时期CCs中糖酵解比卵母细胞更为活跃,由此推测可能是由相应的CCs通过糖酵解提供主要的能量。有趣的是,我们发现在卵母细胞成熟后期,CCs中脂肪酸和胆固醇代谢通路上相关基因的表达水平显著升高。转录组数据提示以脂肪酸和胆固醇为主的脂质代谢生物学过程活跃,说明CCs在卵母细胞成熟过程表现为通路激活。脂肪酸以脂滴(LDs)形式储存于卵泡中,可能是卵母细胞甚至胚胎发生的更有效的能量来源。此外,胆固醇为成熟卵母细胞提供局部孕酮积累,为受精做准备。总之,我们的数据表明,卵母细胞从GV-MII成熟过程中,转录组学上经历了巨大的变化,CCs从卵子GV-MI-MII过程中转录组学上的变化较小。CCs或许不仅在GV期通过糖酵解提供能量底物,还在卵母细胞成熟后期合成脂质和孕酮,以帮助受精和胚胎发育。揭示了卵母细胞成熟过程中卵母细胞与CCs转录机制的独特特征,为进一步研究CCs与卵母细胞在生长发育过程中的相互交流提供了参考。图10幅,表1个,参考文献52篇更多还原

【Abstract】 For human reproduction,a fully developed oocyte is indispensable.The maturation of the oocyte located in the center of the cumulus-oocyte complex(COC)is an extraordinarily complicated process that depends on not only the oocyte itself but also crosstalk between the oocyte and the surrounding cumulus granulose cells(CCs).However,the energetic crosstalk between the oocyte and CCs during oocyte maturation remains unclear.Here,we performed micro-transcriptomic profiling of oocyte and their CCs from 47 preimplantation genetic testing for aneuploidy(PGT-A)patients to explore the relationship between energy metabolism in the oocyte and CCs at different maturation stages(GV,MI and MII).We found that oocyte maturation was a dynamic process and MI oocyte may be subdivided into early MI oocyte and late MI oocyte.The energy consumption of GV oocyte was relatively vigorous.Due to glycolysis in CCs was more active than oocyte during this period,it was speculated that CCs may provide the main energy source through glycolysis.Interestingly,we found that the expression of genes related to fatty acids(FAs)and cholesterol metabolism pathways were significantly increased in CCs at the late stage of oocyte maturation,which suggested that FAs and cholesterol-based lipid metabolism biological processes were active.FAs are stored in follicles in the form of lipid droplets(LDs)and may be a more efficient source of energy for oocyte and even embryogenesis.Moreover,cholesterol provided local high progesterone for mature oocyte in preparation for fertilization.Taken together,our data suggested that oocyte underwent dramatic changes in the transcriptome during maturation from GV-MII,with less changes occurred in CCs during this process.CCs may not only provide energy substrates through glycolysis during the GV phase,but also synthesize lipids and progesterone in late oocyte maturation to aid fertilization and embryonic development.It provides a reference for further study on the metabolic interaction between oocyte and CCs in maturation and development by revealing unique features in the transcriptional machinery of oocyte and CCs during oocyte maturation.更多还原