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Recombinant human TNFα (rhTNFα) has previously been shown to reduce fecundity in  Schistosoma mansoni  adult females maintained  in vitro  without males, and adversely affect the uptake of [ 14 C]-tyrosine, an amino acid required for schistosome vitellogenesis. Here we report on the effect of rhTNFα on [ 14 C]-methionine uptake in both separated and paired females, and the effect of three different preparations of rTNFα on schistosome oviposition  in vitro . In the absence of rhTNFa, separated females incorporated only 30% of the [ 14 C]-methionine incorporated by paired females in a dose and time-dependent manner, suggesting low metabolic activity of females in the absence of males. Separated females and worm-pairs were treated with increasing doses of rhTNFα for 2 or 4 hr and then incubated in RPMI 1640 containing 10% fetal calf serum (FCS) and 5 µCi ml −1 [ 14 C]-methionine for 1 hr. Separated females treated with rhTNFa for 4 hr incorporated less methionine than those treated for 2 hr. In contrast, paired females treated with rhTNFa incorporated significantly smaller amounts of [ 14 C]-methionine in a TNFa dose-dependent but time-independent manner [2 hr (P = 0.001) or 4 hr (P = 0.027) One-Way ANOVA]. Worm-pairs maintained in RPMI 1640 containing 10% FCS and 100 ng ml −1  of any of the three rTNFa preparations laid significantly fewer eggs than the worms cultured without rTNFα(P = 0.001; Kruskal-Wallis Test). We also observed that among rTNFα-treated worm-pairs, females were sluggish and tended to separate from their male partners. These observations suggest that TNFa inhibits [ 14 C]-methionine uptake and reduces fecundity in females paired with males. Since paired females incorporate substantially greater amounts of [ 14 C]-methionine, the role of males in stimulating metabolic activity in females is affirmed. Reduced amino acid uptake, and possibly other nutrients, may contribute to the diminished fecundity observed in TNFa-treated females.

Reduced [ 14 C]-methionine uptake and fecundity in Schistosoma mansoni females treated with recombinant tumor necrosis factor α in vitro