Abstract
Aotearoa faces a pressing biodiversity issue caused by introduced mammalian pests. Possums, stoats, rats and feral cats endanger indigenous flora and fauna. The current approach to pest management relies heavily on dispersal of 1080 poison and trapping, which are effective lethally but can kill non-target species, causing suffering and be labour-intensive. An alternative, humane approach would be to specifically ablate cells with reproductive capabilities. This project aims to impede the fertility of target species specifically by evaluating the efficacy of two cytotoxin drugs, saporin and D-(KLAKLAK)2, conjugated to a targeting molecule. The cytotoxins are hypothesized to become internalized in the targeted cells, induce apoptosis and thereby impede reproductive capacity.
Female mice were injected, first with the saporin-conjugate given peripherally (3μM/animal, n=3), and then D-(KLAKLAK)2-conjugate injected centrally (1μM/animal, n=4) alongside a matching control group injected with saline. Reproductive capacity was measured by following the estrous cycles of these mice and analysing the mean time spent in each cycle phase compared to controls. Brain samples are currently being assessed to identify whether the saporin-conjugate is localising to target cells utilizing a fluorescently tagged saporin variant for tracking. Data was analysed with a two-way ANOVA and presented as mean ± standard error of the mean.
Saporin-conjugate animals spent more time in the metestrus and diestrus phases compared to controls (72.2 ± 11.1% vs 46.1 ± 8.4%, P<0.05), and the time spent in estrus was reduced (16.7 ± 8.3% vs 41.7 ± 8.3%, P<0.05). D-(KLAKLAK)2-conjugate animals showed no significant changes compared to controls in time spent at each phase (P<0.05).
These data suggest that the saporin-conjugate caused disturbances to estrous cyclicity of female mice reflecting a possible inhibition of reproductive capability, but the D-(KLAKLAK)2-conjugate did not achieve the same result. Further studies will evaluate the impact of higher doses on ablating target reproductive cells.