Cellular origins of testicular dysgenesis in rats exposed in utero to di(n-butyl) phthalate
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Cellular origins of testicular dysgenesis in rats exposed in utero to di(n-butyl) phthalate. / Mahood, I Kim; McKinnell, Chris; Walker, Marion; Hallmark, Nina; Scott, Hayley; Fisher, Jane S; Rivas, Ana; Hartung, Stefan; Ivell, Richard; Mason, J Ian; Sharpe, Richard M.
In: INT J ANDROL, Vol. 29, No. 1, 01.02.2006, p. 148-54; discussion 181-5.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Cellular origins of testicular dysgenesis in rats exposed in utero to di(n-butyl) phthalate
AU - Mahood, I Kim
AU - McKinnell, Chris
AU - Walker, Marion
AU - Hallmark, Nina
AU - Scott, Hayley
AU - Fisher, Jane S
AU - Rivas, Ana
AU - Hartung, Stefan
AU - Ivell, Richard
AU - Mason, J Ian
AU - Sharpe, Richard M
PY - 2006/2/1
Y1 - 2006/2/1
N2 - Foetal exposure of male rats to di(n-butyl) phthalate (DBP) induces testicular changes similar to testicular dysgenesis syndrome in humans, including the formation of focal 'dysgenetic areas' within post-natal testes, surrounded by otherwise normal tubules exhibiting complete spermatogenesis. We hypothesize that these dysgenetic areas form when Sertoli (and other) cells are 'trapped' during the abnormal formation of large Leydig cell (LC) clusters in foetal life and by post-natal day (d) 4 these groups of intermingled cells attempt to form seminiferous tubules. It is likely that the malformed tubules resulting correspond to the dysgenetic areas evident in later life. This also provides a plausible explanation for the occurrence of LCs within seminiferous cords/tubules in or bordering the dysgenetic areas. In our previous studies intratubular LCs (ITLCs) were identified by immunostaining for 3beta-hydroxysteroid dehydrogenase (3beta-HSD), the definitive LC cytoplasmic marker. However, the possibility remained that the 'presumptive' ITLCs were in fact Sertoli cells that had aberrantly gained the ability to express 3beta-HSD. Therefore, the aim of the present study was to fully characterize the ITLCs induced by in utero DBP exposure in d25 rats using a number of LC- (3beta-HSD, P450 side-chain cleavage enzyme, insulin-like factor 3, oestrogen receptor alpha) and Sertoli cell- (vimentin, Wilm's tumour-1) specific markers. Our results show that ITLCs express all four LC-specific markers but do not express either of the Sertoli cell markers. It is therefore concluded that the ITLCs are bona fide LCs that are abnormally located within the seminiferous tubules of DBP-exposed rats in post-natal life.
AB - Foetal exposure of male rats to di(n-butyl) phthalate (DBP) induces testicular changes similar to testicular dysgenesis syndrome in humans, including the formation of focal 'dysgenetic areas' within post-natal testes, surrounded by otherwise normal tubules exhibiting complete spermatogenesis. We hypothesize that these dysgenetic areas form when Sertoli (and other) cells are 'trapped' during the abnormal formation of large Leydig cell (LC) clusters in foetal life and by post-natal day (d) 4 these groups of intermingled cells attempt to form seminiferous tubules. It is likely that the malformed tubules resulting correspond to the dysgenetic areas evident in later life. This also provides a plausible explanation for the occurrence of LCs within seminiferous cords/tubules in or bordering the dysgenetic areas. In our previous studies intratubular LCs (ITLCs) were identified by immunostaining for 3beta-hydroxysteroid dehydrogenase (3beta-HSD), the definitive LC cytoplasmic marker. However, the possibility remained that the 'presumptive' ITLCs were in fact Sertoli cells that had aberrantly gained the ability to express 3beta-HSD. Therefore, the aim of the present study was to fully characterize the ITLCs induced by in utero DBP exposure in d25 rats using a number of LC- (3beta-HSD, P450 side-chain cleavage enzyme, insulin-like factor 3, oestrogen receptor alpha) and Sertoli cell- (vimentin, Wilm's tumour-1) specific markers. Our results show that ITLCs express all four LC-specific markers but do not express either of the Sertoli cell markers. It is therefore concluded that the ITLCs are bona fide LCs that are abnormally located within the seminiferous tubules of DBP-exposed rats in post-natal life.
KW - Androgen Antagonists
KW - Animals
KW - Dibutyl Phthalate
KW - Disease Models, Animal
KW - Female
KW - Humans
KW - Leydig Cells
KW - Male
KW - Maternal Exposure
KW - Pregnancy
KW - Prenatal Exposure Delayed Effects
KW - Rats
KW - Rats, Wistar
KW - Sertoli Cells
KW - Testis
U2 - 10.1111/j.1365-2605.2005.00574.x
DO - 10.1111/j.1365-2605.2005.00574.x
M3 - SCORING: Journal article
C2 - 16466534
VL - 29
SP - 148-54; discussion 181-5
IS - 1
ER -