Gene Therapy Restores Fertility in Male Mice
Jan. 28, 2002 -- In the U.S., one in 10 couples struggles with infertility. Researchers are furiously looking for the causes of this troubling problem and ways to treat it. And now, a new study explains how gene therapy has taken one step toward conquering male infertility in mice.
When a couple has problems with fertility, 40% of the time, the problem is with the man. In another 40% of infertility cases, it's the woman who has the difficulty. In the remaining cases, there are fertility issues in both the man and the woman.
In the current study, Japanese researchers report on the first successful use of gene therapy to treat infertility. The study appears in the Feb. 5 issue of the Proceedings of the National Academy of Sciences.
Lead author Mito Kanatsu-Shinohara and colleagues were specifically looking at a genetic cause of infertility in male mice that renders them unable to produce mature, functioning sperm.
Gene therapy usually uses a harmless virus that is equipped with a normal copy of the defective gene. The normal copy of the gene should replace the abnormal one and restore function. The researchers injected the virus/gene combination into the male mice.
Giving the normal copy of the gene restored the mice's ability to produce mature sperm. The problem was, the numbers of normal sperm were still low. But using a procedure commonly used in humans called intracytoplasmic sperm injection, or ICSI, the sperm were able to fertilize eggs and produce embryos.
In ICSI, a sperm is removed from the man and an egg from the woman. The sperm is injected directly into the egg using a very small tube. If fertilization occurs, an embryo begins to develop and is implanted into the woman's womb a few days later.
In this study, the embryos developed into normal, healthy mice. One concern with gene therapy is that the DNA of the virus will show up in the mouse -- or human -- in which it is injected. This did not occur in these mice -- an indication that this is a good virus to use for this purpose.
The genetic defect that produces infertility in male mice is not known to occur in humans. However, there are several genetic causes of infertility in men -- defects of the Y "male" chromosome or of DNA in the testicles.
The researchers say they believe that the success of this procedure in male mice offers a promising treatment for infertility in men whose problems have a genetic cause. They say it also has potential as a treatment for men with unknown causes of infertility.