Lipid droplet synthesis is associated with angiogenesis in mouse ovarian follicles
Lipid droplet synthesis is associated with angiogenesis in mouse ovarian follicles
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DOI：
10.1093/biolre/ioac223
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发表时间：
2023-01-08
影响因子：
3.6
通讯作者：
Tsukamoto，Satoshi
中科院分区：
文献类型：
--
作者：
Ibayashi，Megumi;Aizawa，Ryutaro;Tsukamoto，Satoshi
脂滴（LD）是内质网（ER）衍生的细胞器，其包括被磷脂单层包围的中性脂质核心。脂滴在脂质代谢和能量平衡中起重要作用。哺乳动物卵巢被假设为使用储存在LD中的中性脂质来产生快速卵泡发育所需的激素和营养物质;然而，我们对LD合成的理解仍然不完整。在这项研究中，我们产生了转基因报告小鼠，表达mCherry融合到HPos，一个最小的肽，专门定位于新生LD在ER合成。有了这个工具，可视化初始LD合成卵巢，我们发现，LD是连续合成的卵泡膜细胞，但很少在内部颗粒细胞（GC）在早期卵泡发育。外源性促性腺激素的管理增强LD的合成在GC，表明LD的合成是经尿道调节。相反，我们观察到大量的LD在黄体中的合成，以及过多的LD在闭锁卵泡中的积累。此外，我们证明了LD合成与卵泡周围的血管生成同步，并且抑制血管生成会导致发育中的卵泡中LD生物合成缺陷。总体而言，我们的研究是第一个证明在哺乳动物卵泡发育过程中LD合成和新生血管形成之间存在时空调节的相互作用。
Lipid droplets (LDs) are endoplasmic reticulum (ER)-derived organelles comprising a core of neutral lipids surrounded by a phospholipid monolayer. Lipid droplets play important roles in lipid metabolism and energy homeostasis. Mammalian ovaries have been hypothesized to use neutral lipids stored in LDs to produce the hormones and nutrients necessary for rapid follicular development; however, our understanding of LD synthesis remains incomplete. In this study, we generated transgenic reporter mice that express mCherry fused to HPos, a minimal peptide that localizes specifically to nascent LDs synthesized at the ER. With this tool for visualizing initial LD synthesis in ovaries, we found that LDs are synthesized continuously in theca cells but rarely in inner granulosa cells (Gc) during early follicular development. Administration of exogenous gonadotropin enhances LD synthesis in the Gc, suggesting that LD synthesis is hormonally regulated. In contrast, we observed copious LD synthesis in the corpus luteum, and excessive LDs accumulation in atretic follicles. Furthermore, we demonstrated that LD synthesis is synchronized with angiogenesis around the follicle and that suppressing angiogenesis caused defective LD biosynthesis in developing follicles. Overall, our study is the first to demonstrate a spatiotemporally regulated interplay between LD synthesis and neovascularization during mammalian follicular development.