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Research finds sperm's 'on' switch

21 March 2016
Appeared in BioNews 844

Researchers have discovered a receptor on the cell membrane of sperm that is vital for their activation.

In response to progesterone in the female reproductive tract, the ABHD2 receptor triggers a cascade that powers the sperm to penetrate and fertilise the egg.

The findings, published in Science, suggest that this knowledge may aid in developing new contraceptive methods as well as new treatments for infertility resulting from problems with sperm mobility.

'If the receptor protein doesn’t recognise progesterone, you would be infertile,' Dr Melissa Miller, first author of the paper from University of California, Berkeley, told Medical Daily. 'What is really cool is that we have an actual target for unisex contraceptive development.'

The researchers say it had previously been difficult to study how sperm work due to US laws restricting funding for research bringing sperm and eggs together in the same dish. However, a new technique developed by the authors enabled them to record how sperm behave in response to different hormones by attaching electrodes to their tails.

Previous research showed that a calcium channel referred to as CatSper is activated by progesterone, which is released after ovulation.

In the current study, the researchers found that progesterone was not acting directly on CatSper itself, but to an enzyme called ABHD2 which, in turn, activates the calcium channel.

Once progesterone binds to the enzyme, which sits on the surface of the sperm, it removes a lipid called 2AG that has been inhibiting the calcium channel. This opens the channel to allow calcium ions to enter, leading the sperm to release a 'power kick' that can propel them towards the egg.

The researchers said that the findings could lead to new diagnostics and treatments for male infertility, as well as new types of contraceptives designed to prevent sperm from reaching the egg.

But study author Dr Polina Lishko from the University of California, Berkeley, told BioNews that although the contraceptive aspect of the research had captivated the media, other implications of the research were potentially of greater value.

Dr Lishko said that the signalling pathway they identified could be active in other tissues and processes.

'This lipid molecule, 2AG, is known to regulate huge variety of physiological processes: short term memory, pain, obesity, smooth muscle contraction etc. Thus, it means that any other tissue that expresses ABHD2 (and ABHD2 is expressed in neurons and smooth muscles) would be regulated by progesterone in similar manner,' she said.

Dr Lishko also said that their research produced a complete sperm transcriptome which could be very useful to other researchers. Mature sperm do not transcribe genes but they do contain mRNA from their time as precursor cells, which can tell researchers which genes have been expressed.

She added: 'Sperm cells are very species specific, so mouse or bovine sperm databases do not necessarily reflect what is going on in human sperm cells. Now, since we have a map of what is in human sperm cells, we can make a huge leap in understanding human sperm physiology on a molecular level.'

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