A study reveals that a molecular handshake may exist between cells of the uterus and sperm that may help sperm evade attack by the female immune response.
According to the paper published in the Journal of Biological Chemistry, the researchers showed for the first time an interaction between immune receptors on uterine cells and the complex 'sugar coating' on the surface of sperm cells. The researchers concluded that this 'handshake' may regulate the female immune attack on sperm, helping healthy sperm survive and faulty sperm to be destroyed.
Professor Pascal Gagneux, principal investigator of the study at the University of California, San Diego, said: 'My elevator spiel is that all of life is one big compromise. [For an egg cell], being too easy to fertilise is bad; being too difficult to fertilise is also bad.'
It takes some 200 million sperm to fertilise one solitary egg. This unlikely ratio has arisen because the vast majority of sperm entering the uterus are attacked and killed by cells of the immune system. As Gagneux explains: 'After crossing the cervix, millions of sperm – a US population worth of sperm – that arrive in the uterus are faced by a barrage of [immune cells] macrophages and neutrophils.'
This mass culling by the immune system, known as the leukocytic reaction, whittles millions of sperm down to a few hundred that enter the fallopian tube. Although the leukocytic reaction is not fully understood, it's believed to be one of a series of pre-fertilisation events that reduce the risk of polyspermy – where an egg is fertilised by more than one sperm and cannot develop.
Based on previous research, Gagneux and his team initially thought the complex sugar coating on the surface of sperm, known as glycans, might directly interact with immune cells; however, they did not see much of a response when they tested this. Instead, they discovered the presence of immune receptors along the female reproductive tract that can bind to the sperm glycans, protecting them from the immune response en route to fertilisation.
The researchers plan to follow up this work using intact uterine tissue to better understand this 'secret handshake' and determine if it helps sperm dampen the immune system or uterine cells weed out faulty sperm.
'It's somewhat embarrassing how little we can say about what this [interaction] means,' said Gagneux, adding that it was 'humbling' to work in such a poorly understood field. '[Reproduction] is a very, very delicate tug-of-war at many levels. The fact that there is (also) this immune game going on is completely fascinating.'