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氧水平改变牛植入前胚胎的能量代谢。

Oxygen level alters energy metabolism in bovine preimplantation embryos.

作者信息

Boskovic Nina, Ivask Marilin, Yazgeldi Gunaydin Gamze, Yaşar Barış, Katayama Shintaro, Salumets Andres, Org Tõnis, Kurg Ants, Lundin Karolina, Tuuri Timo, Daub Carsten O, Kere Juha

机构信息

Department of Medicine Huddinge, Karolinska Institutet, 14183, Huddinge, Sweden.

Department of Obstetrics and Gynecology, University of Helsinki, 00290, Helsinki, Finland.

出版信息

Sci Rep. 2025 Apr 2;15(1):11327. doi: 10.1038/s41598-025-95990-z.

Abstract

Mammalian preimplantation embryo development is a complex sequence of events. This period of development is sensitive to oxygen (O) levels that can affect various cellular processes. We compared the influence of O tension by culturing embryos either in normoxic (20% O) or physiological hypoxic (6% O) conditions, or sequential low O concentration starting with 6% O until 16-cell stage and then switching to ultrahypoxic conditions (2% O). Due to ethical concerns, we used bovine as an animal model with a good similarity of embryogenesis to human. We found that the cleavage rate was not affected by O levels but there was a clear difference in blastocyst formation rate. In hypoxia, 36% of embryos reached blastocyst stage while in normoxia only 13%. In ultrahypoxia conditions only 4.6% of embryos developed up to blastocyst stage. Transcriptomic profiles showed that normoxic conditions slowed down oocyte transcript degradation which is a prerequisite for reprogramming of the embryonic cell lineages. There were also clear differences in the expression of key metabolic enzymes between hypoxic and normoxic conditions at the blastocyst stage. Both hypoxic and ultrahypoxic conditions seemed to induce appropriate energy production by upregulating genes involved in glycolysis and lipid metabolism typical to in vivo embryos. In contrast, normoxic conditions failed to upregulate glycolysis genes and only depended on oxidative phosphorylation metabolism. We conclude that constant hypoxia culture of in vitro embryos provided the highest blastocyst formation rate and appropriate energy metabolism. Normoxia altered the energy metabolism and decreased the blastocyst formation rate. Even though ultrahypoxia at blastocyst stage resulted in the lowest blastocyst formation, the transcriptional profile of surviving embryos was normal.

摘要

哺乳动物植入前胚胎发育是一系列复杂的事件。这一发育阶段对氧(O)水平敏感,氧水平会影响各种细胞过程。我们通过在常氧(20% O)或生理低氧(6% O)条件下培养胚胎,或从6% O开始直至16细胞期采用连续低氧浓度培养然后切换至超低氧条件(2% O),比较了氧张力的影响。出于伦理考虑,我们使用牛作为动物模型,其胚胎发生与人类有很好的相似性。我们发现卵裂率不受氧水平影响,但囊胚形成率存在明显差异。在低氧条件下,36%的胚胎达到囊胚阶段,而在常氧条件下只有13%。在超低氧条件下,只有4.6%的胚胎发育至囊胚阶段。转录组图谱显示,常氧条件减缓了卵母细胞转录本的降解,而这是胚胎细胞谱系重编程的一个先决条件。在囊胚阶段,低氧和常氧条件下关键代谢酶的表达也存在明显差异。低氧和超低氧条件似乎都通过上调参与糖酵解和脂质代谢的基因来诱导适当的能量产生,这是体内胚胎的典型特征。相比之下,常氧条件未能上调糖酵解基因,仅依赖氧化磷酸化代谢。我们得出结论,体外胚胎的持续低氧培养提供了最高的囊胚形成率和适当的能量代谢。常氧改变了能量代谢并降低了囊胚形成率。尽管囊胚阶段的超低氧导致囊胚形成率最低,但存活胚胎的转录谱是正常的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c99/11965477/d6ef028944f7/41598_2025_95990_Fig1_HTML.jpg

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