Voices of Change

C. Yan Cheng: Mediating the Effects of a Toxic Environment

C. Yan Cheng is a senior scientist at the Population Council's Center for Biomedical Research. His research focuses on the development of a novel contraceptive for human males. He is also the editor-in-chief of the quarterly, peer-reviewed journal  Spermatogenesis.

In recent years, we're finding that the quality of men's semen is going down. Not only in terms of sperm mobility, but also in the number of sperm produced. About 30 percent of cases of couples' infertility can be attributed to the man these days. There are increasing numbers of studies that link poor sperm performance with cadmium. Men who have difficulty conceiving babies have significantly higher levels of cadmium in their body fluids, such as semen, than men with normal fertility.

Cadmium is a very common environmental toxicant. It's used in the manufacture of batteries and pigments. Industrial activities, such as the refining and smelting of metals and municipal waste incineration, also release cadmium to the atmosphere. This means that the general population is exposed to cadmium via contaminants found in drinking water and food. Smokers are exposed to high levels of cadmium, since each cigarette has a small amount of cadmium in it. If you smoke one pack of cigarettes a day, you inhale an additional one to three micrograms of cadmium in addition to the microgram each of us ingests each day. McDonald's used paint that contained cadmium on some drinking glasses it gave away; in the dishwasher the cadmium could leach onto other dishes. McDonald's recalled 12 million of these glasses. Cadmium has a very long half life of between 20 and 40 years. Because it mimics calcium, it's absorbed into your body and ends up staying in your body for a long time, especially the bones, liver, and kidneys.

I started studying cadmium in the course of doing research on a possible male contraceptive. The seminiferous tubule is where the final stage of sperm formation occurs. Inside the seminiferous tubule are two types of cells, Sertoli cells and germ cells. Sertoli cells are what I call the mommy cells. Germ cells are the babies that eventually become sperm. Each Sertoli cell in the seminiferous tubule takes care of about 40 or 50 germ cells. Protecting the seminiferous tubule is something called the blood–testis barrier (BTB), which is formed by tight connections between Sertoli cells. Sertoli cells mediate what crosses the BTB, and the reason the BTB exists is to prevent the passage of substances toxic to germ cells into the seminiferous tubule.

We found out that high doses of cadmium destroy the BTB over a relatively short period, about 20 hours. I realized that if I could inject cadmium into an animal and then study the timeframe in which the destruction of the BTB occurred, I might be able to figure out the sequence of events and the genes and proteins involved at certain times. Then maybe I could develop a way to open the BTB momentarily, but not completely destroy it. Our findings have also identified potential therapeutic molecular targets to block the disruptive effects of cadmium in the testis.

It's important to figure out a way to temporarily disrupt the BTB, because this will allow the delivery of important drugs, including contraceptives. I've been studying the contraceptive effects of a drug called adjudin that was derived from a very toxic anticancer drug called lonidamine. When adjudin makes its way into the seminiferous tubule, it disrupts communication between Sertoli cells and germ cells so that the germ cells don't have the opportunity to mature into sperm. The intact BTB doesn’t allow adjudin to pass through. If we can figure out how to temporarily open the BTB to allow adjudin in, we will be on our way to developing an effective male contraceptive for men.