Mice, Men and Babies

You probably never thought you would be asked to decide what role a rat's testicles should play in the birth of your child. But the modern world is full of choices. Perhaps the ultimate choice, and

May 13, 1999 at 2:06 pm

You probably never thought you would be asked to decide what role a rat's testicles should play in the birth of your child. But the modern world is full of choices.

Perhaps the ultimate choice, and the ultimate responsibility, is whether or not to have children. To that end, couples experiencing fertility problems spend millions of dollars each year on the medical assistance that might increase their chances of conception. Soon, a controversial therapy that uses the testicles of rodents might provide would-be parents with a whole new set of choices and some difficult ethical questions to address. So, if you think it would be hard to tell your child that he or she is adopted, imagine telling him that he spent a few months being incubated inside the gonads of a rat called Benny.

Both infertility and rodents have been around ever since our much hairier, and slightly sillier, descendants began chasing one another around the campfire millions of years ago. Throughout history, infertility frequently was considered to be a solely feminine problem. Consequently, many women were blamed, labeled as barren and unfairly shunned by society.

We now know that reduced fertility is as frequently a result of complications in males as in females.

The causes of male infertility are numerous and range from the effects of injuries, environmental pollutants and genetic deletions to hot baths and tight pants. The way they exert their effects on fertility are as varied as the causes themselves. It should be noted, however, that many of these factors have been studied separately and, consequently, the effects of wearing tight pants in a hot bath are not yet known.

Although the possible causes of male infertility are many, they act to bring about only two common effects. Either sperm production is reduced, thereby lowering the probability of fertilization, or the sperm or reproductive system are damaged in such a way as to prevent successful migration to an otherwise viable egg. In some men, this is attributed to the production of sperm with misshapen bodies or completely absent tails while, in others, it is due to sperm that have no endurance, little sense of direction and cannot swim well. Coincidentally, many men have no endurance, little sense of direction and cannot swim well either. But this does not necessarily correlate with a low sperm count.

Regardless, in more and more cases, successful therapy for male infertility exists. This often consists of removal of the causative agents wherever possible and sometimes includes additional prescription of various therapeutic drugs. Frequently, in vitro-fertilization, or IVF, might help in which sperm and egg are brought into closer proximity with one another to increase the likelihood of conception.

Some complications cannot be overcome by IVF. This usually is because of the complete absence of sperm production. Such a complaint is due to failure of the sperm precursor cells, or spermatogonia, to proceed along the normal developmental cycle that results in mature sperm.

This vital process normally occurs in the seminiferous tubules of the testes and any interruption of the system has generally been considered a problem for which no remedy exists.

In 1996, however, a team of University of Pennsylvania scientists discovered that transplantation of rat spermatogonia into mice testes resulted in cells that produced healthy rat sperm capable of fertilizing rat eggs. Researchers were quick to ask whether human sperm could successfully be manipulated in the same way and made to grow in the testicles of different species.

Nikolaos Sofikitis, of Tottori University in Japan, was the first to answer in the affirmative. By sufficiently disrupting the immune response of rodents, he was able to transplant spermatogonia from the testicles of infertile men to those of mice and rats. Five months after transplantation, mature and healthy human sperm were detectable in the testes of both the mice and the rats.

Despite resistance from groups with ethical concerns, Sofikitis immediately applied to the Japanese government for permission to experiment further by actually fertilizing human eggs with the sperm harvested from rodents. Many of the ethical and scientific concerns raised were extremely valid. More cautious researchers called for the procedure to first be repeated in nonhuman primates to ascertain whether transplantation was possible in animals that exhibited greater species differences than those that existed between rats and mice. With initial data being obtained from only rodent to rodent transplantation, the effects on human sperm could not be accurately predicted. It is highly possible, and even expected, that a system as far removed from the human reproductive system could significantly and negatively affect the genetic information carried by the sperm.

Although, if you ask Sevetino Antinori he'll tell you that's not a problem. Antinori, an Italian reproductive specialist, claimed during a March news conference that he already had used the technique to successfully produce four babies, the eldest of which is almost a year old.

He previously has garnered extensive media attention by overseeing the successful IVF treatment of a 67-year-old woman. So, this is merely the latest in an impressive catalogue of ethically questionable achievements.

Not surprisingly, people will find this latest development shocking and will oppose it. Many find this level of interference unsettling and perhaps the fact that Antinori disregarded the fears of other specialists even more so. The average childless couple, however, probably will find it much easier to justify such a procedure if it affords them new options.

It also is important to realize that such advances have many other widespread benefits. Research on human sperm always has been complicated in that, by definition, it has to be carried out in humans. This no longer will be true should these techniques be mandated. The new findings also might expedite the development of efficacious male contraceptives, again, due to the availability of human sperm and an alternative system within which to study them. This might prove to be a vital development in the slowing of an unchecked and alarming rate of birth in the Third World.

So, maybe fewer babies will be born that aren't wanted and more will be born that are. That really can't be a bad thing. It just depends on whether we can resolve ourselves to the methods by which we accomplish such a positive outcome.

A concern shared by many is that we might only be aware of the negative effects when they are observed and characterized for the first time. As with many new technologies, a system that has not been adequately investigated has been prematurely used. Inevitably, many more fears and reservations yet will be raised before spermatogonia transplantation can be considered a routine treatment for infertility in this country.

Furthermore, before you give your local doctor a call, it also is likely that we will see the advent of new laws preventing its use until more is known of its reliability, So there's no need to go to the local pet store to try and select a suitable rat just yet.

And hopefully, if it ever does become a valid treatment, I will have had time to get over my fear of Ricki Lake hosting a show titled: "You came from a rat's testicle, and you ain't all that!"