Dr. Deepak Modi (left) and Vrushali Sagare-Patil found low levels of heat shock protein 90 (HSP90) in sperm reduces motility and causes infertility in men.

A Mumbai-based team of researchers has identified one more protein — heat shock protein 90 (HSP90) — found in human sperm that determines the ability of sperm to vigorously whip their tail and move or swim (motility) faster towards an egg to fertilise it. The reduced ability of sperm to move towards the egg is one of the causes of infertility in men. The results were published recently in the Journal of Assisted Reproduction and Genetics.

Studying groups of infertile men to find the causes of male infertility, the researchers observed that men with poor sperm motility have very low amounts of HSP90 in the sperm. In men with greater percentage of highly motile sperm, the amount of the protein in the sperm was higher.

The protein is present in two forms — HSP90 alpha and HSP90 beta. While the alpha form is present in the junction between the head and midpiece of a sperm, the beta form is found in the tail. This is the first time the presence and abundance of the two forms of the protein in certain parts of the sperm has been reported.

“HSP90 beta is dominant in the tail. So we thought the motility is regulated by HSP90 beta isoform” says Dr. Deepak Modi at ICMR’s National Institute for Research in Reproductive Health (NIRRH), Mumbai and the corresponding author of the paper.
At any time, sperm keep moving at a slow speed (basal motility) but in the presence of progesterone hormone, which is found in the female reproductive tract, the motility of sperm suddenly increases. It is this increased motility due to the hormone that helps sperm to travel the long distance to reach the egg.

To ascertain whether the protein is needed for motility, the researchers used two drugs to inhibit the protein in vitro. “The basal motility of sperm was unaffected. But when we added progesterone hormone to sperm (which had the functions of HSP90 already inhibited by the drugs) we did not see sperm move faster and forward,” Dr. Modi says.

Basal motility

“HSP90 protein is not the only one that is responsible for motility. So inhibition of this protein alone may not affect basal motility. Thus we got interested in looking at the effect of progesterone-induced motility,” says Vrushali Sagare-Patil from NIRRH and the first author of the paper.

While the basal motility is not dependent on HSP90, the protein is required to increase the motility of sperm when exposed to progesterone hormone. “If a man has low amounts of HSP90 protein in his sperm, the sperm will be unable to swim upwards to the tubes and fertilize the egg because it cannot feel the effects of progesterone. This will be a cause of infertility,” Dr. Modi says.

“So the progesterone-driven motility requires additional machinery. One of the components is the HSP90 protein,” he says.

Drug development

The information about the crucial role of HSP90 protein can help scientists develop drugs to make sperm move faster and forward in the female reproductive tract in people who low sperm motility.

“At present there is no treatment for male infertility due to poor sperm motility caused by genetic causes” says Dr Indira Hinduja an IVF expert at Mumbai’s Hinduja Hospital and a co-author of the paper. There is a possibility that this work might help the development of drugs that would help enhance sperm motility by restoring the functions of the protein.

Conversely, contraceptives can be developed to inhibit the protein so that sperm do not move faster and reach the egg to fertilise it even in the presence of the hormone.

Published in The Hindu on March 4, 2017