Abstract

Schistosomes infect over 200 million people. The prodigious egg output of these parasites is the sole driver of pathology due to infection, yet our understanding of sexual reproduction by schistosomes is limited because normal egg production is not sustained for more than a few days in vitro. Here, we describe culture conditions that support schistosome sexual development and sustained egg production in vitro. Female schistosomes rely on continuous pairing with male worms to fuel the maturation of their reproductive organs. Exploiting these new culture conditions, we explore the process of male-stimulated female maturation and demonstrate that physical contact with a male worm, and not insemination, is sufficient to induce female development and the production of viable parthenogenetic haploid embryos. We further report the characterization of a nuclear receptor (NR), which we call Vitellogenic Factor 1 (VF1), that is essential for female sexual development following pairing with a male worm. Taken together, these results provide a platform to study the fascinating sexual biology of these parasites on a molecular level, illuminating new strategies to control schistosome egg production.

Highlights

  • Schistosomes are blood-dwelling parasitic flatworms that cause serious disease in millions of people in the developing world [1]

  • Capitalizing on these culture conditions, we further report the characterization of a previously uncharacterized nuclear receptor (NR) that is essential for normal female development following pairing with a male worm

  • As previously reported [15], adult schistosomes recovered from mice and cultured in Basch’s “medium 169” (BM169) progressively lost the ability to lay eggs with the morphological characteristics of those laid in vivo or immediately ex vivo (Fig 1A)

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Summary

Introduction

Schistosomes are blood-dwelling parasitic flatworms that cause serious disease in millions of people in the developing world [1]. The pathology caused by these parasites is entirely due to the parasite’s prodigious egg output [2]. The goal of the parasite is to pass these eggs from the host to ensure the continuity of the parasite’s complex life cycle, approximately half of these eggs become trapped in host tissues, inducing inflammation that represents the primary driver of disease [3]. Since parasites incapable of producing eggs produce little pathology in infected hosts, understanding the biology of schistosome egg production could suggest new therapeutic strategies aimed at diminishing the pathogenesis and spread of these devastating parasites. Schistosomes are unusual among flatworms because they do not sexually reproduce as hermaphrodites.

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