Authors

Discussion

The human parasitic flatworm Schistosoma mansoni genome encodes more than 260 protein kinases, important regulatory proteins that are highly conserved across eukaryotes. Our previous studies demonstrated that the exchange of male or female excretory-secretory products (ESPs) between groups of opposite-sex adult worms rapidly activated the p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated kinase (ERK) pathways within the worms. Moreover, treatment with SB203580 and U0126 significantly attenuated the ESP-mediated phosphorylation (activation) of p38 MAPK and ERK, respectively. Next, to investigate stem cell proliferation, Click-it EdU and Alexa Fluor staining were performed in in vitro cultured worms. In homosexual culture, adult males and females exhibited a significant cell proliferation reduction over six days, compared to day zero controls. Remarkably, however, exposure to opposite sex ESPs significantly increased cell proliferation in the testicular lobes of males, ovaries and vitellaria of females, and the surface tegument layer of both sexes. This effect was attenuated by either SB203580 or U0126, highlighting the involvement of p38MAPK and ERK pathways in the ESP-mediated responses. We next conducted proteomic analysis of the male/female ESPs, revealing 705 proteins in total, with 583 common to males and females, and 74 and 48 exclusively present in ESPs of the male and female, respectively. Analysis of extracellular vesicle (EV)-depleted fractions revealed 362 proteins in total, 286 in common, and 62 and 14 exclusive to males and females respectively. Although the molecules responsible for stimulating responses in opposite sex worms have not yet been definitively identified, future research aims to elucidate the nature of the critical ESPs and further characterise their effects on opposite sex worms. These findings provide valuable insights into male-female schistosome interactions that might open potential avenues for the development of novel strategies to control schistosomiasis, a disease affecting over 240 million people.