Signal transduction regulates schistosome reproductive biology

Abstract

Schistosome parasites exhibit separate sexes and with the evolution of sex they have developed an intricate relationship between the male and female worms such that signals between the male and female that are initiated at the time of mating, regulate female reproductive development and subsequent egg production. As the egg stage is responsible for pathogenesis and transmission, understanding the molecular mechanisms of female reproductive development may identify novel targets for the control of transmission and morbidity of this major world public health problem. Recent data have demonstrated that the pairing process, proliferation, and differentiation of vitelline cells, expression of female-specific genes and egg embryogenesis are regulated by the TGFbeta pathway and protein tyrosine kinases.

Figure 1

Female Schistosoma mansoni, showing (a) an immature female from a single-sex infection that is stunted and reproductively underdeveloped, (b) female lying in the gynecophoric canal of a male, (c) a mature female from a bisexual infection showing that the posterior 2/3rds of the body is comprised of the vitellaria (V) that develops in response to pairing; O, ovary (d) enlargement of the mature female reproductive system. Oocytes produced in the ovary are released into an oviduct. A dilitated region in the oviduct, the seminal receptacle, is the site of fertilization. The fertilized egg moves down the oviduct to a region where it meets the vitelline duct, the vitello-oviduct. Here, each fertilized egg is surrounded by approximately 38 vitelline cells. This bolus of material moves into the ootype which is filled with mucus secretions presumably from the Mehlis' gland. With the contraction of the ootype, which determines the shape of the egg, granules are released from the surrounding vitelline cells. The materials from the granules (vitelline droplets) begin to crosslink, due to the action of a tyrosinase enzyme(s) and the eggshell forms. The egg (f) which contains the fertilized egg and a number of vitelline cells that each contain nutrients for embryogenesis is released into the uterus and one at a time deposited by the female worm through the gonopore, (e) Mature vitelline cell (S4) containing the vitelline droplets (VD) and (f) just formed egg containing the zygote and numerous vitelline cells that will contribute to embryonation. (Modified from [41])

Figure 2

TGFβsignaling pathway in male Schistosoma mansoni showing signaling from the female to the male that contributes to parasite pairing (based on experimental data). The cartoon depicts surface-exposed tegument of the gynecophoric canal. SmTGFβtype II receptor (RII) binds a parasite or a host TGFβ ligand (SmInAct, hTGFβ1). The ligand/RII complex triggers the interaction with a type I receptor (RIA; SmTβRI), phosphorylates and activates it. The activated type I receptor relays the signal down to a R-Smad (RIA to SmSmad2), where the SmSmad2 is activated via phosphorylation. The activated SmSmad2 interacts with the co-Smad (SmSmad4) in the subtegument. The SmSmad complex translocates to the nucleus of the sub-tegumental cell, binds nuclear partners and the assembled transcription complex binds to the Smad binding element in the promoter of the target gene (SmGCP) and regulates target gene transcription. The SmGCP transcript is translated and the protein transported to the surface of the gynecophoric canal where it facilitates worm pairing. See text and [3, 6, *10] for further details.(modified from [6]).