Deciphering the loss of fertility in ivermectin-treated Brugia malayi females in vitro: a transcriptomic approach [Study II]

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. Overall design: Transcriptomic changes over several different time points and concentrations.

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Ballesteros C, Tritten L, O'Neill M, Burkman E, Zaky WI, Xia J, Moorhead A, Williams SA, Geary TG