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不饱和脂肪酸是生殖系增殖和[具体生物名称]膜结构完整性所必需的。

Unsaturated Fatty Acids Are Required for Germline Proliferation and Membrane Structural Integrity in .

作者信息

Battista Bernabe, Lascarez-Lagunas Laura I, de Mendoza Diego, Colaiácovo Monica P

机构信息

Institute of Molecular and Cellular Biology of Rosario, National University of Rosario (IBR-CONICET-UNR) Ocampo y Esmeralda, Rosario 2000, Argentina.

Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.

出版信息

bioRxiv. 2025 Jul 29:2025.07.24.666670. doi: 10.1101/2025.07.24.666670.

Abstract

Unsaturated fatty acids (UFAs) are critical components of membrane lipids, but their specific roles in germline development and reproductive health remain poorly defined. Here, we investigated the consequences of UFA depletion in the s germline using an auxin-inducible degron (AID) system to conditionally degrade FAT-7, the major Δ9 stearoyl-CoA desaturase, in a double mutant background. This strategy bypassed the lethality associated with complete loss of Δ9 desaturase activity, enabling analysis of UFA deficiency in adult animals. UFA depletion led to a dramatic reduction in brood size, elevated embryonic and larval lethality, and a severe loss of germline nuclei. We found that UFAs are essential for mitotic proliferation, DNA replication, and chromosome organization in the germline. Moreover, reduced UFA levels impaired meiotic progression, accompanied by loss of membrane integrity in the syncytial germline. Notably, UFA deficiency increased nuclear pore complex (NPC) signal intensity, suggesting alterations to the nuclear envelope (NE). Together, our findings demonstrate that UFAs are indispensable for germline maintenance, affecting cell cycle progression, chromosome organization, and membrane architecture. These results underscore a fundamental link between acyl chain composition and reproductive success, highlighting the critical role of lipid homeostasis in the germline.

摘要

不饱和脂肪酸(UFAs)是膜脂的关键组成部分,但其在生殖系发育和生殖健康中的具体作用仍不清楚。在这里,我们利用生长素诱导降解子(AID)系统,在双突变背景下有条件地降解主要的Δ9硬脂酰辅酶A去饱和酶FAT-7,研究了生殖系中UFA缺失的后果。该策略绕过了与Δ9去饱和酶活性完全丧失相关的致死性,从而能够分析成年动物中UFA缺乏的情况。UFA缺失导致产卵量显著减少、胚胎和幼虫致死率升高以及生殖系细胞核严重丧失。我们发现,UFA对生殖系中的有丝分裂增殖、DNA复制和染色体组织至关重要。此外,UFA水平降低会损害减数分裂进程,并伴随着合胞体生殖系中膜完整性的丧失。值得注意的是,UFA缺乏会增加核孔复合体(NPC)信号强度,表明核膜(NE)发生了改变。总之,我们的研究结果表明,UFA对生殖系维持不可或缺,影响细胞周期进程、染色体组织和膜结构。这些结果强调了酰基链组成与生殖成功之间的基本联系,突出了脂质稳态在生殖系中的关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0884/12324212/6922d57441a4/nihpp-2025.07.24.666670v1-f0001.jpg

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