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Abstract
Mixed cultures of Sertoli and germ cells were prepared from rat testes and their response
to some model testicular toxins was studied. Cultures consisted of a monolayer of
Sertoli cells to which clusters of spermatocytes and spermatogonia adhered. With time
in culture, germ cells progressively detached from the Sertoli cells into the medium.
Addition of mono-(2-ethylhexyl) phthalate (MEHP) to the culture medium resulted in
a concentration-dependent increase in the rate of germ-cell detachment over the range
10(-7) - 10(-4) M. No such effect was produced by di-(2-ethylhexyl) phthalate or 2-ethylhexanol.
An increased rate of germ-cell detachment was also produced by other phthalate monoesters
known to cause testicular damage in vivo, whereas similar concentrations of a number
of monophthalates not known to affect the testis in vivo had no such effect on the
cultures. Known age and species differences in the testicular toxicity of di-(2-ethylhexyl)
phthalate could be reproduced in cultures treated with MEHP. There was little effect
on the viability of either germ cells or Sertoli cells at concentrations of MEHP that
caused marked germ-cell detachment, but there were changes in Sertoli-cell morphology.
Increased germ-cell detachment was also observed in cultures treated with 10(-7) -
10(-4) M-AF1312/TS, a compound that affects Sertoli cells in vivo, but was not seen
in cultures exposed to a range of other testicular toxins with different target cells
in the testis. Thus, the effects produced by phthalate monoesters in vitro may reflect
damage to the Sertoli cells. Testicular cell cultures could be of value both for screening
compounds and for studying underlying mechanisms of testicular toxicity.