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Maternal lipid mobilization is essential for embryonic development in a key malaria vector

ABSTRACT: Lipid metabolism is an essential component in reproductive physiology. While lipid mobilization has been implicated in the growth of Plasmodium falciparum malaria parasites in their Anopheles vectors, the role of this process in the reproductive biology of these mosquitoes remains elusive. Here, we show that impairing lipolysis in Anopheles gambiae, the major malaria vectors, leads to embryonic lethality. Embryos derived from females in which we silenced the triglyceride lipase AgTL2 or the lipid storage droplet AgLSD1 develop normally during early embryogenesis but fail to hatch. These embryos show severely impaired metabolism and appear to have compromised neuronal functions. Embryonic lethality is efficiently recapitulated by exposing adult females to broad-spectrum lipase inhibitors prior to blood feeding, unveiling lipolysis as a novel target for inducing mosquito sterility. Our findings provide mechanistic insights into the importance of maternal lipid mobilization in embryonic health that could potentially inform studies on human reproduction.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - alternating - hilic, Liquid Chromatography MS - positive - hilic, Liquid Chromatography MS - positive - reverse phase, Liquid Chromatography MS - negative - hilic

PROVIDER: MTBLS9881 | MetaboLights | 2024-11-05

REPOSITORIES: MetaboLights

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			Action	DRS
	Blank_Lip_neg_1.mzML	Mzml
	Blank_Lip_neg_2.mzML	Mzml
	Blank_Lip_neg_3.mzML	Mzml
	GFP_Lip_neg_06h_1.mzML	Mzml
	GFP_Lip_neg_06h_2.mzML	Mzml

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Project description:We explored the role of triglyceride (TAG) mobilization in the reproductive success of female Anopheles gambiae after a blood meal. Silencing triglyceride lipase 2 (TL2) in An. gambiae reduced egg production and abrogates fertility. Embryos from AgTL2-depleted females develop normally but fail to hatch and are characterized by reduced levels of lipids and key metabolites, including carbohydrates, Tricarboxylic acid (TCA) intermediates, paralleled by increased levels of purine and pyrimidine breakdown products, signifying possible cellular death. To obtain a better understanding of the mechanism underlying embryonic lethality in AgTL2-deficient females, we generated RNA-Seq datasets of tissues and embryos from control and TL2-knockdown females at different time points after blood feeding (for tissues) and oviposition. These analyses revealed that while at earlier time points there is almost no difference, transcriptomic profiles at the later time point of 38 hours after laying were profoundly distinct between both groups. Specifically, pathways involved in neuropeptide signaling, G-protein coupled receptor signaling, and eclosion hormone synthesis were repressed in TL2-knockdown condition while hallmarks of cellular stress were significantly up-regulated. More importantly, pathways involved in de novo lipid synthesis and transport were significantly up-regulated, possibly to compensate for reduced levels of maternally inherited lipids.

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Transcriptomic analysis of tissues and embryos from control and triglyceride lipase 2 (TL2)-deficient Anopheles gambiae females.

Project description:Transcriptomic analysis of tissues and embryos from control and triglyceride lipase 2 (TL2)-deficient Anopheles gambiae females.

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