The contraceptive pill, implants or injections all contain synthetic versions of certain female hormones. These contraceptives are not suitable for everyone, as they may cause side effects such as mood changes, nausea and breakthrough bleeding. Also, none of these contraceptives protect against sexually transmitted infections. We are interested in developing non-hormonal contraception by blocking embryo implantation. Our strategy is to utilise our understanding of embryo implantation to target key proteins and prevent implantation.
We are interested in a range of implantation regulators for contraception development, one of which is proprotein convertase (PC) 6, a member of the PC serine protease family. PC enzymes convert numerous proteins from their non-active precursors into bioactive forms. PCs are therefore important regulatory molecules in generating a large number of tissue-specific and functionally important bioactive proteins. These proteins include growth factors, peptide hormones, adhesion molecules, and HIV envelope proteins. PCs are therefore regarded as promising targets for various therapeutic applications.
We have discovered that PC6 in the uterus is critical for embryo implantation. Preventing PC6 production in the mouse uterus leads to a complete failure of implantation, while blocking PC6 function in human cells inhibits the equivalent critical step of implantation. What makes this discovery even more important is that PCs, including PC6, also play a critical role in HIV infection through the activation of HIV envelope proteins. This makes PC6 an exciting target for preventing pregnancy and HIV infection at the same time (a “double whammy” female contraceptive).
We have developed an in vitro model of human embryo implantation using cell embryo “mimetics”; this model is suitable for sensitive and high throughput screening for implantation inhibitors. Our research program is developing different ways to inhibit PC6 to prevent embryo implantation in animals, and in cell models relevant to human implantation. Our ultimate goal is to develop a novel female non-hormonal contraceptive method that could also protect women from HIV infection.
Dr Jian Wang (Shanghai Institute of Planned Parenthood Research, Shanghai, China)
Dr Zhaogui Sun (Shanghai Institute of Planned Parenthood Research, Shanghai, China)
Dr Tracy Nero (Bio21, Melbourne, Australia)
Prof Michael Parker (Bio21, Melbourne, Australia)
Dr Guan-Sheng Jiao (PanThera Biopharma LLC, Hawaii, USA)