A NEW XENOGRAFT TESTICULAR CANCER MODEL

NEW YORK (Reuters Health) Aug 03 - U.K. scientists hope their new xenograft model of human fetal testis tissue will shed light on the fetal origins of testicular germ cell tumors and infertility.

The xenografts demonstrate normal structure, function and development, including normal germ cell differentiation, Dr. Richard M. Sharpe from the University of Edinburgh and colleagues say in an August 4th online article in Human Reproduction.

"If the authors' technique can be replicated by others, it would be a substantial advance because currently we have no models of human testicular tissue that allow us to understand both how exogenous factors alter the normal development of the testes, and how characteristics such as host genetics and other molecular features might be interacting with exogenous factor," Dr. Stephen M. Schwartz said in an email to Reuters Health.

"As the authors point out, mostly what is available now are rodent models or cell lines, and these require some pretty big leaps of inference to the human situation," he added. Dr. Schwartz, from the Fred Hutchinson Cancer Research Center in Seattle, was not involved in the research.

The difference between the current model and previous attempts at xenografting human testes is that Dr. Sharpe's team used testes obtained after first-trimester (9 weeks) and second-trimester (14-18 weeks) pregnancy terminations.

Testis tissue was placed subcutaneously in castrated male nude mice, then retrieved after 6 weeks. According to the report, more than 75% of the grafts survived with normal morphology.

In the first-trimester xenografts, normal appearing seminiferous cords developed. The older grafts produced Sertoli, Leydig and peritubular myoid cells comparable to age-matched controls. Grafts produced testosterone, especially when the mice had been treated with human chorionic gonadotropin.

Moreover, germ cells differentiated from gonocytes into pre-spermatogonia and proliferated.

Now that they have a model of normal testicular development, the researchers plan to study genetic and environmental factors related to disorders in sex development and later testicular dysgenesis syndrome.

"There are a number of exogenous factors that are of interest for their possible effect on testicular development, including chlorinated pesticides (e.g., DDE) and industrial products (e.g., PCBs), bisphenol A, and phthalates, just to name a few," Dr. Schwartz told Reuters Health. "These could all be tested using such a system."

"From my own research we have identified associations between marijuana use and testicular cancer risk that would be important to study in xenograft models," he added.

SOURCE: Abstract

Hum Reprod 2010.