One more reason for infertility in women

There are many reasons for a man or woman to be infertile. A recent finding adds one more to this list for infertility in women. A joint research in Germany, by Professor Dr. Walter Stöcker of the Institute of Zoology at Johannes Gutenberg University Mainz (JGU) and a team led by Professor Dr. Willi Jahnen-Dechent of the Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, have found a new mechanism involving a protein Fetuin-B secreted by liver for infertility and the discovery has a potential therapeutic value.

The joint venture of the two teams, have found out for the first time that premature hardening of ovum may prevent the entry of sperms leading to infertility.

Soon after fertilization, a cascade of reactions called as “cortical reaction” sets in that makes the outer most region the Zona Pellucida (ZP) of the fertilized ovum hard. Normally, this hardening of ZP is essential to prevent subsequent sperm penetration of the ovum, in other words the hardening of ZP stops a condition called polyspermy. Polyspermy results in the death of the embryo and thus leads to infertility. 

Team headed by Professor Dr. Walter Stöcker has already been working on the mechanism of the cortical reaction. They found out that the hardening of the ZP is triggered by a proteolytic enzyme called ovastacin stored in small vesicles within the ovum. When a sperm enters an ovum for the first time, the entry triggers an explosive release of ovastacin into the gap between the egg cell and the zona pellucida which ultimately makes ZP hard. The story doesn’t stop there, normally there is a constant low level release of the enzyme ovastacin. If the action of this ‘background’ ovastacin is not prevented, then it may lead to the hardening of ZP. This premature hardening of ovum may prevent the entry of sperms leading to infertility. 

The team led by Professor Dr. Willi Jahnen-Dechent, discovered that female mice lacking a protein called fetuin-B were infertile even though they had a normal functional ovaries. They could successfully restore fertility by restoring normal fetuin-B production.

Jointly both the teams have found out a new role for Fetuin-B which is formed in the liver and released into the blood stream in low quantities. They discovered that Fetuin-B is actually an inhibitor of ovastacin which prevents the background ovastacin activity so that oocytes does not become hard even before fertilization.

After a sperm has penetrated an egg cell, the cortical reaction will trigger the release of huge amounts of ovastacin that will overwhelm the inhibitory capacity of fetuin-B and initiate the hardening process of ZP to prevent polyspermy.

-Dr. P. Kumarasamy

Further reading:

http://www.sciencenewsline.com/summary/2013042415120010.html 

http://www.cell.com/developmental-cell/abstract/S1534-5807(13)00132-9

http://www.sciencedirect.com/science/article/pii/S1534580713001329

http://www.sciencedaily.com/releases/2012/04/120402124335.htm

http://www.uscnk.com/directory/Fetuin-A(FETUA)-1860.htm

http://www.biolreprod.org/content/early/2013/04/12/biolreprod.113.110171.abstract