A previous study in the rat (Pollard et al. 1990)
established that caffeine, when administered during pregnancy, significantly
inhibited the differentiation of the seminiferous cords and subsequent Leydig
cell development in the interstitium. However, that study could not
distinguish between the direct effects of caffeine and/or the intermediary
secondary toxic effects of metabolites such as theophylline and theobromine.
Because the fetus lacks the appropriate enzyme systems, clearance of toxic
substances takes place via the placenta and maternal liver. Thus, a suitable
in vitro system can effectively differentiate between
primary and secondary drug effects. In the present study, 13-day-old fetal
testis, at the stage of incipient differentiation, were cultured for 4 days
in vitro in the presence of graded doses of caffeine,
theophylline or theobromine. It was found that explants exposed to caffeine or
theobromine differentiated normally, developing seminiferous cords made up of
Sertoli and germ cells, soon followed by the differentiation of functionally
active Leydig cells appearing in the newly formed interstitium. However,
explants exposed to theophylline failed to develop seminiferous cords and, as
a consequence, Leydig cells. In conclusion, insights obtained from different
experimental methods, such as organ culture or whole organism studies, are not
always identical. It may be prudent, therefore, to take into account that
certain experimental techniques, despite providing valuable information, may
require confirmation by other test methods in order to obtain an in-depth
understanding of mechanisms of action involved.
