Synthesis and maintenance of lipid droplets are essential for mouse preimplantation embryonic development
Synthesis and maintenance of lipid droplets are essential for mouse preimplantation embryonic development
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DOI：
10.1242/dev.181925
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发表时间：
2019-11-15
期刊：
影响因子：
4.6
通讯作者：
Tsukamoto, Satoshi
中科院分区：
文献类型：
--
作者：
Aizawa, Ryutaro;Ibayashi, Megumi;Tsukamoto, Satoshi
脂滴是细胞内普遍存在的一种细胞器，由中性脂质核心包裹磷脂单层构成，在细胞脂质代谢的调节中起着重要作用。虽然众所周知哺乳动物卵母细胞和胚胎含有LD，并且LD的量在动物物种之间变化，但它们的生理功能仍然不清楚。在这项研究中，我们开发了一种基于两步离心的方法，用于有效地去除小鼠MII卵母细胞中几乎所有的LD（脱脂）。我们发现，脱脂的MII卵母细胞可以在体外受精，并正常发育到囊胚期，即使胚胎培养在没有脂肪酸供应。LDs是新的合成和积累脱脂后不久，但化学抑制长链酰基辅酶A合成酶（ACSL）阻断这一过程，导致早期胚胎发育严重受损。此外，我们发现过量的LD对早期胚胎发育不利。我们的研究结果表明，在植入前胚胎发育过程中，部分由ACSL活性介导的LD合成和维持的重要性。
Lipid droplets (LDs), which are ubiquitous organelles consisting of a neutral lipid core coated with a phospholipid monolayer, play key roles in the regulation of cellular lipid metabolism. Although it is well known that mammalian oocytes and embryos contain LDs and that the amount of LDs varies among animal species, their physiological functions remain unclear. In this study, we have developed a method based on two-step centrifugation for efficient removal of almost all LDs from mouse MII oocytes (delipidation). We found that delipidated MII oocytes could be fertilized in vitro, and developed normally to the blastocyst stage even when the embryos were cultured in the absence of a fatty acid supply. LDs were newly synthesized and accumulated soon after delipidation, but chemical inhibition of long chain acyl-CoA synthetases (ACSLs) blocked this process, resulting in severe impairment of early embryonic development. Furthermore, we found that overabundance of LDs is detrimental to early embryonic development. Our findings demonstrate the importance of synthesis and maintenance of LDs, mediated in part by ACSL activity, during preimplantation embryonic development.