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Danustouch
August 20th, 2001, 01:11 PM
a possible lead in the race to find a MALE birth control pill???????

Protein essential for male fertility in the mouse identified




Last Updated: 2001-05-03 18:33:40 EDT (Reuters Health)


By Megan Rauscher


WESTPORT, CT (Reuters Health) - Scientists have identified a protein in male mice that plays a crucial role in the very early stages of fertilization. In the May 4th issue of Science, they report that an isoform of phospholipase C (PLC), PLCdelta4, which is predominately expressed in the testis, mediates the zona pellucida-induced acrosome reaction, a key event in fertilization.


Until now, "there has been no report which identified the protein involved in the acrosome reaction at the molecular level," lead researcher Dr. Kiyoko Fukami, of The University of Tokyo, Japan, told Reuters Health.


The scientists report that fertility is severely impaired in male, but not female, PLCdelta4 knockout mice. Male PLCdelta4-null mice "either produced few small litters or were sterile," they write.


In in vitro fertilization studies, the majority of PLCdelta4-null eggs that were fertilized with PLCdelta4-null sperm failed to enter the blastocyst stage. PLCdelta4 mutant sperm were also unable to initiate timely calcium oscillations associated with fertilization, according to the team.


Dr. Fukami noted, in comments to Reuters Health, that about 10% of male factor infertility is due to an abnormality of acrosome reaction. "Continued efforts to analyze the function of PLCdelta4 will assist in elucidating the molecular mechanisms underlying mammalian fertilization and may have implications in the field of contraception," Dr. Fukami's group concludes in the journal.


"The development of drugs that would either prematurely induce, or, prevent the acrosome reaction, could have a great impact in the development of techniques for male contraception," Dr. Fukami continued. "In the future, it might be possible, either through the knockout technique or via expression of a transgene, to closely regulate the expression of this protein in a manner that the fertility of a male could be turned on or off according to the expression of the targeted protein, in this case PLCdelta4. In this manner, we would be creating a reversible male contraception system that has, so far, remained elusive."


Science 2001;292:920-923.


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