Deciphering the loss of fertility in ivermectin-treated Brugia malayi females in vitro: a transcriptomic approach
Ontology highlight
ABSTRACT:
ORGANISM(S): Brugia malayi
PROVIDER: GSE75341 | GEO | 2016/07/27
SECONDARY ACCESSION(S): PRJNA303984
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-07-27 | E-GEOD-75341 | biostudies-arrayexpress
Project description:In this study, we analyzed transcriptomic profiles from ivermectin-treated and -untreated B. malayi adult females using Next Generation RNA Sequencing technology at different concentrations (100 nM, 300 nM and 1 µM) and time points (24, 48, 72 h, and 5 days). Our analysis revealed altered expression of multiple genes involved in meiosis, as well as oxidative phosphorylation which were significantly down-regulated as early as 24 hours post-exposure. RNA interference phenotypes of the orthologs of these down-regulated genes in C. elegans include “maternal sterile”, “embryonic lethal”, “larval arrest”, “larval lethal”, “reduced brood size” and “egg shape variable”. These changes reflect and provide insight into the mechanisms involved in ivermectin-induced reduction in microfilaria output and impaired fertility, embryogenesis, and larval development.
2016-07-27 | GSE75340 | GEO
Project description:In this study, we analyzed transcriptomic profiles from ivermectin-treated and -untreated B. malayi adult females using Next Generation RNA Sequencing technology at different concentrations (100 nM, 300 nM and 1 µM) and time points (24, 48, 72 h, and 5 days). Our analysis revealed altered expression of multiple genes involved in meiosis, as well as oxidative phosphorylation which were significantly down-regulated as early as 24 hours post-exposure. RNA interference phenotypes of the orthologs of these down-regulated genes in C. elegans include “maternal sterile”, “embryonic lethal”, “larval arrest”, “larval lethal”, “reduced brood size” and “egg shape variable”. These changes reflect and provide insight into the mechanisms involved in ivermectin-induced reduction in microfilaria output and impaired fertility, embryogenesis, and larval development.
2016-07-27 | GSE75339 | GEO
Project description:In this study, we analyzed transcriptomic profiles from ivermectin-treated and -untreated B. malayi adult females using Next Generation RNA Sequencing technology at different concentrations (100 nM, 300 nM and 1 µM) and time points (24, 48, 72 h, and 5 days). Our analysis revealed altered expression of multiple genes involved in meiosis, as well as oxidative phosphorylation which were significantly down-regulated as early as 24 hours post-exposure. RNA interference phenotypes of the orthologs of these down-regulated genes in C. elegans include âmaternal sterileâ, âembryonic lethalâ, âlarval arrestâ, âlarval lethalâ, âreduced brood sizeâ and âegg shape variableâ. These changes reflect and provide insight into the mechanisms involved in ivermectin-induced reduction in microfilaria output and impaired fertility, embryogenesis, and larval development. Transcriptomic changes over several different time points and concentrations.
2016-07-27 | E-GEOD-75339 | biostudies-arrayexpress
Project description:In this study, we analyzed transcriptomic profiles from ivermectin-treated and -untreated B. malayi adult females using Next Generation RNA Sequencing technology at different concentrations (100 nM, 300 nM and 1 µM) and time points (24, 48, 72 h, and 5 days). Our analysis revealed altered expression of multiple genes involved in meiosis, as well as oxidative phosphorylation which were significantly down-regulated as early as 24 hours post-exposure. RNA interference phenotypes of the orthologs of these down-regulated genes in C. elegans include âmaternal sterileâ, âembryonic lethalâ, âlarval arrestâ, âlarval lethalâ, âreduced brood sizeâ and âegg shape variableâ. These changes reflect and provide insight into the mechanisms involved in ivermectin-induced reduction in microfilaria output and impaired fertility, embryogenesis, and larval development. Transcriptomic changes over several different time points and concentrations.
2016-07-27 | E-GEOD-75340 | biostudies-arrayexpress
Project description:BackgroundLymphatic filariasis and onchocerciasis are disabling and disfiguring neglected tropical diseases of major importance in developing countries. Ivermectin is the drug of choice for mass drug administration programs for the control of onchocerciasis and lymphatic filariasis in areas where the diseases are co-endemic. Although ivermectin paralyzes somatic and pharyngeal muscles in many nematodes, these actions are poorly characterized in adult filariae. We hypothesize that paralysis of pharyngeal pumping by ivermectin in filariae could result in deprivation of essential nutrients, especially iron, inducing a wide range of responses evidenced by altered gene expression, changes in metabolic pathways, and altered developmental states in embryos. Previous studies have shown that ivermectin treatment significantly reduces microfilariae release from females within four days of exposure in vivo, while not markedly affecting adult worms. However, the mechanisms responsible for reduced production of microfilariae are poorly understood.Methodology/principal findingsWe analyzed transcriptomic profiles from Brugia malayi adult females, an important model for other filariae, using RNAseq technology after exposure in culture to ivermectin at various concentrations (100 nM, 300 nM and 1 μM) and time points (24, 48, 72 h, and 5 days). Our analysis revealed drug-related changes in expression of genes involved in meiosis, as well as oxidative phosphorylation, which were significantly down-regulated as early as 24 h post-exposure. RNA interference phenotypes of the orthologs of these down-regulated genes in C. elegans include "maternal sterile", "embryonic lethal", "larval arrest", "larval lethal" and "sick".Conclusion/significanceThese changes provide insight into the mechanisms involved in ivermectin-induced reduction in microfilaria output and impaired fertility, embryogenesis, and larval development.
| S-EPMC4986938 | biostudies-literature
Project description:Deciphering the loss of fertility in ivermectin-treated Brugia malayi females in vitro: a transcriptomic approach
| PRJNA303984 | ENA
Project description:Ivermectin (IVM) is a broad-spectrum anthelmintic used in filariasis control programs. By binding to nematode glutamate-gated chloride channels (GluCls), IVM disrupts neurotransmission processes regulated by GluCl activity. IVM treatment of filarial infections is characterized by an initial dramatic drop in the levels of circulating microfilariae, followed by long-term suppression of their production, but the drug has little direct effect on microfilariae in culture at pharmacologically relevant concentrations. We localized Brugia malayi GluCl expression solely in a muscle structure that surrounds the microfilarial excretory-secretory (ES) vesicle, which suggests that protein release from the ES vesicle is regulated by GluCl activity. Consistent with this hypothesis, exposure to IVM in vitro decreased the amount of protein released from microfilariae. To better understand the scope of IVM effects on protein release by the parasite, three different expression patterns were identified from immunolocalization assays on a representative group of five microfilarial ES products. Patterns of expression suggest that the ES apparatus is the main source of regulated ES product release from microfilariae, as it is the only compartment that appears to be under neuromuscular control. Our results show that IVM treatment of microfilariae results in a marked reduction of protein release from the ES apparatus. Under in vivo conditions, the rapid microfilarial clearance induced by IVM treatment is proposed to result from suppression of the ability of the parasite to secrete proteins that enable evasion of the host immune system.
| S-EPMC2993382 | biostudies-literature
Project description:Lymphatic filariasis (LF) threatens nearly 20% of the world's population and has handicapped one-third of the 120 million people currently infected. Current control and elimination programs for LF rely on mass drug administration of albendazole plus diethylcarbamazine (DEC) or ivermectin. Only the mechanism of action of albendazole is well understood. To gain a better insight into antifilarial drug action in vivo, we treated gerbils harbouring patent Brugia malayi infections with 6 mg kg-1 DEC, 0.15 mg kg-1 ivermectin or 1 mg kg-1 albendazole. Treatments had no effect on the numbers of worms present in the peritoneal cavity of treated animals, so effects on gene expression were a direct result of the drug and not complicated by dying parasites. Adults and microfilariae were collected 1 and 7 days post-treatment and RNA isolated for transcriptomic analysis. The experiment was repeated three times. Ivermectin treatment produced the most differentially expressed genes (DEGs), 113. DEC treatment yielded 61 DEGs. Albendazole treatment resulted in little change in gene expression, with only 6 genes affected. In total, nearly 200 DEGs were identified with little overlap between treatment groups, suggesting that these drugs may interfere in different ways with processes important for parasite survival, development, and reproduction.
| S-EPMC7994942 | biostudies-literature
Project description:Filarial parasites like Brugia pahangi and Brugia malayi can infect dogs. Adults of Brugia genus resides in the lymphatic system and microfilariae, in blood. There are increasing reports of detection of B. malayi microfilariae in dogs. A study was undertaken to compare the efficacy of repeated oral dosing of ivermectin (IVT) and diethylcarbamazine (DEC), individually and in combination against naturally infected B. malayi microfilariae in dogs. The species of the microfilariae was confirmed by acid phosphatase staining and polymerase chain reaction. The three treatment groups were 200 mcg/kg body weight IVT daily for 14 days (I), 6.6 mg/kg body weight DEC daily for 14 days (II) and IVT and DEC together in the same dose for a period of 5 days (III). Microfilarial status of the peripheral blood was assessed on the 0th, 7th, 14th and 21st day. Haematological parameters were measured on day zero and on the 21st day. Though, all the three treatment groups showed a reduction in the microfilarial concentration through the study period, complete absence of detectable microfilaremia was not noticed in any of the three groups by 21st day. Among the haematological parameters, statistically significant difference was observed in the post-treatment means of haemoglobin levels of group III when compared with group II. Since group III regime (IVT + DEC) was shorter and just as effective as the longer ones, it is considered superior to the other two.
| S-EPMC6841773 | biostudies-literature