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

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 Caenorhabditis elegans germline using an auxin-inducible degron (AID) system to conditionally degrade FAT-7, the major {Delta}9 stearoyl-CoA desaturase, in a fat-5; fat-6 double mutant background. This strategy bypassed the lethality associated with complete loss of {Delta}9 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. SummaryUnsaturated fatty acids (UFAs) are essential for fertility, but their role in germline maintenance remains unclear. In this study, we used Caenorhabditis elegans to examine how UFA depletion affects the germline. By conditionally disrupting UFA synthesis, we found that low UFA levels impair germline mitotic proliferation, DNA replication, meiotic progression, and germline membrane structures. These findings demonstrate that lipid composition is critical for germline maintenance and highlight a broader role for fatty acids in reproductive health, offering insights relevant to metabolic and fertility disorders in humans.