The potential to improve the effectiveness and efficiency of potential estrogen-based oral contraceptives (fertility control) for possums was investigated by comparing the inhibitory potential of hepatic CYP3A and UGT2B catalytic activity using a selected compound library (CYP450 inhibitor-based compounds) in possums to that of three other species (mouse, avian, and human). The results showed higher CYP3A protein levels in possum liver microsomes compared to other test species (up to a 4-fold difference). Also, possum liver microsomes had significantly higher basal p-nitrophenol glucuronidation activity than other test species (up to an 8-fold difference). However, no CYP450 inhibitor-based compounds significantly decreased the catalytic activity of possum CYP3A and UGT2B below the estimated IC₅₀ and 2-fold IC₅₀ values and were therefore not considered to be potent inhibitors of these enzymes. However, compounds such as isosilybin (65%), ketoconazole (72%) and fluconazole (74%) showed reduced UGT2B glucuronidation activity in possums, mainly at 2-fold IC₅₀ values compared to control (p<0.05). Given the structural features of these compounds, these results could provide opportunities for future compound screening. More importantly, however, this study provided preliminary evidence that the basal activity and protein content of two major drug metabolising enzymes differ in possums compared to other test species, suggesting that this could be further exploited to reach the ultimate goal, a potential target-specific fertility control for possums in New Zealand.

The New Zealand brushtail possum (Trichosurus vulpecula), introduced from Australia in the 1850s, is an invasive species that is widespread throughout New Zealand and forms the largest self-sustained reservoir of bovine tuberculosis (Mycobacterium bovis) in the wild. Conservation and agricultural authorities regularly apply a series of population control measures to suppress brushtail possum populations. The evolutionary consequence of more than half a century of intensive population control operations on the species genomic diversity and population structure is hindered by a paucity of available genomic resources for the species. This study is the first to characterise the functional content and diversity of brushtail possum liver and brain cerebral cortex transcriptomes. Raw sequences from hepatic cells and cerebral cortex were assembled into 58,001 and 64,735 transcripts in hepatic cells and cerebral cortex, respectively. Functional annotation and polymorphism assignment of the assembled transcripts demonstrated a considerable level of variation in the core metabolic pathways that represent potential targets for selection pressure exerted by chemical toxicants. This study suggests that the brushtail possum population in New Zealand harbours considerable levels of variation in metabolic pathways that could potentially promote the development of tolerance against chemical toxicants.