Hudson Institute researchers have discovered that inhibiting a protein called SOX17 prevents an embryo mimic from ‘sticking’ to the uterus lining-highlighting potential for a new contraceptive strategy.
Hormone-based contraceptives are used by millions of women worldwide, and have been for decades. Some women face little or no problems with their use, yet others may suffer with several side effects-both those of a less serious nature (weight gain, breakthrough bleeding) and those more severe (an increased risk of blood clots or various cancers).
A non-hormonal strategy
In the first stages of pregnancy, the embryo adheres or ‘sticks’ to the lining of the uterus, known as the endometrium. This is referred to as the implantation phase, and can only occur within a short window of time each menstrual cycle when the endometrium is ready, in a receptive state.
Targeting the endometrium to ensure it remains in a non-receptive state is an alternative approach to contraception, which doesn’t involve hormones.
“Hormone-based contraceptives were designed in the late 1950’s” said Dr Jemma Evans, Deputy Head of the Endometrial Remodelling Lab at Hudson Institute. “Times have changed in the almost 60 years since they were introduced and women’s needs have changed too, so we need to radically rethink contraceptive options.”
A study published in Scientific Reports, led by Dr Jemma Evans and honours student Sophie Kinnear investigated SOX17-a protein that is known to be present in the endometrium when it is in a receptive state.
The researchers inhibited SOX17-using both genetic knockdown and a chemical inhibitor-to study the effect this would have on the implantation phase of a ‘pregnancy’ (in endometrial samples taken from women). The team discovered that inhibiting SOX17 prevented adhesion of an embryo mimic to endometrial cells, suggesting that targeting SOX17 could be a new, non-hormonal contraceptive strategy.
“We found that targeting a critical molecule called SOX17 prevented ’embryos’ from implanting on endometrial cells, which is a critical step in starting pregnancy” said Dr Evans. “This suggests that delivering an inhibitor of SOX17 to the womb, for instance using a vaginally-applied gel containing the SOX17 inhibitor, may be an effective contraceptive strategy.”
A new contraception regime?
The endometrium is only ready for an embryo for around four days each menstrual cycle, so women would only need to use the contraceptive for a short period of time each cycle to prevent pregnancy, or only after intercourse.
In addition, a vaginal gel could be applied to the uterus locally, and therefore would reduce the risk of systemic side effects (occurring in other areas of the body) that other contraception methods may cause.
“Providing a form of contraception which doesn’t need to be used every day, can be managed by the woman herself, and with fewer side-effects than hormone-based contraceptives are the ‘holy grail’ of contraceptive research. That was the motivation for this study” commented Dr Evans.
Millions of women worldwide have an unmet need of reliable contraceptives. Offering a non-hormonal, locally-administered option could help these women live their lives without the risk of systemic side effects and fear of unintended pregnancies.
“These contraceptives could be used together with mobile phone-based menstrual cycle tracking to provide a ‘ping’ reminder to use the treatment when the chance of falling pregnant is highest. This empowers women as they have autonomy over their bodies and contraceptive choices.”
Future research will focus on assessing SOX17 inhibitors in preclinical models, to help make the concept of this contraception become a reality for women.
The yin and yang of fertility
Conversely, by highlighting SOX17’s key role in the implantation phase of pregnancy, the study’s results also suggest a potential opportunity for assisted reproduction technologies, such as IVF.
Up-regulating SOX17 (rather than inhibiting it) could enhance the endometrium’s receptive state and encourage the implantation of an embryo.
Further studies are required to determine whether such a strategy could be a safe and effective option for those who are struggling to conceive-yet these findings provide an exciting new concept.
Collaborators
Professor Vincent Harley, Hudson Institute; Mathias Francois, University of Queensland; Monash University.
Funders
CASS foundation.
