Recent and emerging reproductive biology research in Australia and New Zealand: highlights from the Society for Reproductive Biology Annual Meeting, 2017.

Research in reproductive science is essential to promote new developments in reproductive health and medicine, agriculture and conservation. The Society for Reproductive Biology (SRB) 2017 conference held in Perth (WA, Australia) provided a valuable update on current research programs in Australia and New Zealand. This conference review delivers a dedicated summary of significant questions, emerging concepts and innovative technologies presented in the symposia. This research demonstrates significant advances in the identification of precursors for a healthy pregnancy, birth and child, and discusses how these factors can influence disease risk. A key theme included preconception parental health and its effect on gametogenesis, embryo and fetal development and placental function. In addition, the perturbation of key developmental checkpoints was shown to contribute to a variety of pathological states that have the capacity to affect health and fertility. Importantly, the symposia discussed in this review emphasised the role of reproductive biology as a conduit for understanding the transmission of non-communicable diseases, such as metabolic disorders and cancers. The research presented at SRB 2017 has revealed key findings that have the prospect to change not only the fertility of the present generation, but also the health and reproductive capacity of future generations.

Novel cationic amphiphiles as delivery agents for antisense oligonucleotides.

There has been great interest recently in therapeutic use of nucleic acids including genes, ribozymes and antisense oligonucleotides. Despite recent improvements in delivering antisense oligonucleotides to cells in culture, nucleic acid-based therapy is still often limited by the poor penetration of the nucleic acid into the cytoplasm and nucleus of cells. In this report we describe nucleic acid delivery to cells using a series of novel cationic amphiphiles containing cholic acid moieties linked via alkylamino side chains. We term these agents 'molecular umbrellas' since the cationic alkylamino chains provide a 'handle' for binding of nucleic acids, while the cholic acid moieties are likely to interact with the lipid bilayer allowing the highly charged nucleic acid backbone to traverse across the cell membrane. Optimal gene and oligonucleotide delivery to cells was afforded by a derivative (amphiphile 5) containing four cholic acid moieties. With this amphiphile used as a constituent in cationic liposomes, a 4-5 log increase in reporter gene delivery was measured. This amphiphile used alone provided a 250-fold enhancement of oligo-nucleotide association with cells as observed by flow cytometry. A substantial fraction of cells exposed to complexes of amphiphile 5 and fluorescent oligo-nucleotide showed nuclear accumulation of the fluorophore. Enhanced pharmacological effectiveness of antisense oligonucleotides complexed with amphiphile 5 was observed using an antisense splicing correction assay that activates a Luciferase reporter. Intracellular delivery, nuclear localization and pharmacological effectiveness of oligonucleotides using amphiphile 5 were similar to those afforded by commercial cytofectins. However, in contrast to most commercial cytofectins, the umbrella amphiphile showed substantial delivery activity even in the presence of high concentrations of serum.