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Female contraceptives that also block STDs
Summary
The World Health Organisation has identified a critical need to increase contraceptive options for women. We have shown that blocking cytokine action with unique inhibitors results in total pregnancy failure. We are investigating the effect of delivering these cytokine inhibitors with agents that also block sexually transmitted diseases on pregnancy outcome.
Description
More than 700,000 maternal deaths, most in the developing world and related to causes associated with unintended pregnancies, occurred between 1995 and 2000; more than 400,000 of these deaths resulted from unsafe abortions. For many women, existing contraceptives are therefore not acceptable or not available, and thus in many cases are not used.
Two cytokines, leukaemia inhibitory factor (LIF) and interleukin 11 (IL-11) are absolutely required for embryo implantation in mice and have important roles in embryo-endometrial interactions.
Through our collaborations with industry and non-industry partners we have access to novel LIF and IL-11 inhibitors and have demonstrated that these inhibitors block implantation and lead to pregnancy failure in mice. We are currently investigating whether these inhibitors can be administered in combination with agents that prevent sexually transmitted infections including HIV.
We are further investigating the mechanisms by which LIF and IL-11 act in the endometrium of women at the very early stages of implantation.
This project utilises animal and human cell culture models, state-of-the-art techniques including PHI's protoemics facility.
Funding
National Health and Medical Research Council
Contraceptive Research and Development Agency (CONRAD), USA
The Lalor Foundation, USA
Outcomes
Demonstration that new long-acting inhibitors of specific cytokines can block development of uterine receptivity provides proof of principal that they could be used for contraceptive purposes in women.
Selected Publications
Marwood E, Visser K, LA Salamonsen, E Dimitriadis (2009) Interleukin 11 and leukemia inhibitory factor regulate the adhesion of endometrial epithelial cells: implications in fertility regulation. Endocrinology, 150:2915-23
Menkhorst E, Salamonsen LA, Robb L, Dimitriadis E (2009) IL11 antagonist inhibits uterine stromal cells differentiation causing pregnancy failure in mice. Biology of Reproduction, 80:920-7
White CA, Zhang J-G, Salamonsen LA, Baca M, Fairlie WD, Metcalf D, Nicola NA, Robb L, Dimitriadis E (2007) Blocking leukemia inhibitory factor action in the uterus using a novel PEGylated antagonist prevents implantation: a new non-hormonal contraceptive strategy. Proc Natl Acad Sci USA 104:19357-62. (Work included in an Editorial in Science, 318: 1835 (2007) and PNAS cover feature)
Dimitriadis E Robb L, Liu Y-X, Enders AC, Martin H, Stoikos C, Wallace E and Salamonsen LA (2003) IL-11 and IL-11 ralpha immunolocalisation at primate implantation sites implies a role for IL-11 in placentation and fetal development. Reproductive Biology and Endocrinology, Biomed Central, 1, 34.