# A male-pheromone-elevated transcription factor ZNF362.1 in female schistosomes determines sexual maturation

## TL;DR

A male pheromone triggers a gene in female schistosomes that is crucial for their sexual development, offering new targets for treating schistosomiasis.

## Contribution

Discovery of znf362.1 as a key transcription factor in female schistosome sexual maturation triggered by male pheromones.

## Key findings

- ZNF362.1 is essential for BATT-induced maturation of female schistosome reproductive organs.
- ZNF362.1 activates Smp_349410, a gene encoding a CPEB1 homolog critical for oocyte and vitellocyte differentiation.
- SmCPEB1 regulates cyclin B1 mRNA polyadenylation and S1 cell differentiation in the vitellaria.

## Abstract

Egg production by female schistosomes drives both transmission and pathology of schistosomiasis, affecting over 200 million people. Female maturation relies on the male-derived pheromone β-alanyl-tryptamine (BATT), but underlying molecular mechanisms are unclear. We identified the BATT-responsive transcription factor gene znf362 as a key regulator of female reproductive development. Functional studies showed that znf362.1, but not znf362.2, is essential for BATT-induced ovary and vitellaria maturation. Single-cell transcriptomics and in situ hybridization revealed up-regulation of znf362.1 in oocytes and vitellaria S1 cells after BATT exposure. Multiomics analysis showed ZNF362.1 directly activates Smp_349410, a female gonad-specific gene encoding a CPEB1 homolog. Loss of znf362.1 or Smp_349410 impaired oocyte and vitellocyte differentiation without affecting progenitors. Mechanistically, SmCPEB1 promotes female ovary development by regulating polyadenylation of cyclin B1 mRNA and drives S1 cell differentiation in the vitellaria. These findings define a transcriptional and post-transcriptional axis, BATT-znf362.1-cpeb1, that initiates female sexual maturation, offering mechanistic insight into schistosome reproduction and potential targets for schistosomiasis control.

Female Schistosoma mansoni start sexual maturation upon male signals, highlighting potential therapy targets.