Abstract
Mating causes decreased life span in female Drosophila. Here we report that mifepristone blocked this effect, yielding life span increases up to +68%. Drug was fed to females after mating, in the absence of males, demonstrating function in females. Mifepristone did not increase life span of virgin females or males. Mifepristone reduced progeny production but did not reduce food intake. High-throughput RNA sequencing was used to identify genes up-regulated or down-regulated upon mating, and where the change was reduced by mifepristone. Five candidate positive regulators of life span were identified, including dosage compensation regulator Unr and three X-linked genes: multi sex combs (PcG gene), Dopamine 2-like receptor and CG14215. The 37 candidate negative genes included neuropeptide CNMamide and several involved in protein mobilization and immune response. The results inform the interpretation of experiments involving mifepristone, and implicate steroid hormone signaling in regulating the trade-off between reproduction and life span.
Highlights
Mifepristone (RU486) is a progesterone receptor antagonist and glucocorticoid receptor antagonist with human contraceptive and abortifacient activities, and is in clinical trials for its potential as an anticancer drug [1]
The results indicate that mifepristone may sometimes lead to inflated estimates of female life span increase upon transgene overexpression using Gene-Switch
A small decrease was observed in males in this experiment, negative effect in males was not observed with other genotypes (Table 1)
Summary
Mifepristone (RU486) is a progesterone receptor antagonist and glucocorticoid receptor antagonist with human contraceptive and abortifacient activities, and is in clinical trials for its potential as an anticancer drug [1]. Activated Gene-Switch binds to UAS sites in the promoter of target constructs to yield transgene over-expression. Certain previous studies have included controls for possible effects of mifepristone on life span, typically using the progeny of a driver strain crossed to the non-transgenic control strain w[1118]. We report that mifepristone acts in females to block the negative effect of mating, yielding increased life span for several genotypes, including the popular w[1118] control strain and Elav-Gene-Switch (Elav-GS) driver strain [2]. The results indicate that mifepristone may sometimes lead to inflated estimates of female life span increase upon transgene overexpression using Gene-Switch.
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