Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Expression data from wild type and ttk^twk mutant whole ovaries

ABSTRACT: Epithelial tube morphogenesis requires precise orchestration of cell signaling, shape, migration, and adhesion. Follicle cells in the Drosophila ovary form epithelial tubes, the lumens of which act as molds for the eggshell respiratory filaments, or dorsal appendages (DAs). The Tramtrack69 (TTK69) transcription factor controls DA lumen volume and shape by promoting tube expansion; the tramtrack mutation twin peaks (ttk^twk) reduces TTK69 levels late in oogenesis, inhibiting DA tube expansion. We used microarrays to identify differentially expressed genes in the ttk^twk mutant that are downstream of TTK69 and that play a functional role in DA tube expansion. Ovaries were dissected from female flies at 36 hours of age, to maximize the proportion of developing egg chambers undergoing DA tube expansion. Flies were raised at a constant temperature of 25C in the presence of wet yeast, to maximize the rate of egg chamber production.

ORGANISM(S): Drosophila melanogaster

SUBMITTER: Nathaniel Peters

PROVIDER: E-GEOD-42758 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Per- and polyfluoroalkyl substances (PFAS) are persistent pollutants known for their bio-accumulative properties and prevalence in water supplies and household products. Although legacy PFAS, such as perfluorooctanoic acid, are phased out in the U.S. due to public health concerns, a PFAS variant hexafluoropropylene oxide-dimer acid (HFPO-DA) is an emerging replacement. HFPO-DA is a potential neurotoxicant that has been shown to cause dopaminergic neurodegeneration. We investigated the bioaccumulative potential of HFPO-DA and its effects on lifespan, locomotor activity, and brain gene expression in female and male Drosophila melanogaster (fruit flies). Flies were collected less than 4 hours post-eclosion and exposed to 0, 10, 10^2, 10^3, or 10^4 mg/kg/day HFPO-DA. To measure the effect of HFPO-DA on lifespan, surviving flies from each exposure were recorded every 24 hours. Flies were subjected to a negative geotaxis assay at 3, 7, and 14 days of exposure to measure the effects of acute, sub-chronic, and chronic exposures on locomotor ability. To capture HFPO-DA-induced sexually dimorphic gene expression responses in the brain, we sequenced brain-specific mRNA from flies exposed for 3, 7, or 14 days. The Bioconcentration Factor was 0.031 for females, and 0.026 for males. Dose and median lifespan were negatively correlated in both female (R^2 adj = 0.77, p<0.0001) and male flies (R^2 adj = 0.77, p<0.0001). Log-rank Mantel-Cox tests and one-way ANOVAs revealed that median lifespan was reduced in females starting at 10 mg/kg/day and in males starting at 10^2 mg/kg/day (p< 0.01). Acute exposure at 10 mg/kg/day significantly decreased locomotor ability in females (p<0.0001) while acute exposures at 1 mg/kg/day decreased locomotor activity in males (p <0.0001). Among 7500 genes analyzed, pairwise gene expression comparison between controls and treatments identified 2496 differentially expressed genes. While HFPO-DA does not readily bioaccumulate in fruit fly bodies, high-dose exposures have sex-specific effects on lifespan, locomotor ability, and brain gene expression. LOAEL for median lifespan is 10 mg/kg/day in females, and 10^2 mg/kg/day in males. Both locomotor ability and brain gene expression exhibited non-conventional dose-response as seen in other endocrine disrupting chemical exposures.

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Expression data from wild type and ttk^twk mutant whole ovaries

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