Carbendazim (CBZ), a widely used fungicide, induces in vivo severe testicular alterations in rats. However, its cellular and molecular mechanisms of action are not completely understood. We used the validated rat seminiferous tubule culture model to test the effects of concentrations of CBZ at least 60-fold lower than the serum concentrations found in rats treated with high doses of CBZ. Seminiferous tubules from pubertal rats were treated with CBZ 50 nM, 500 nM, or 5 μM over a 3-week culture period. The trans-epithelial electrical resistance was slightly increased by CBZ from day 16 onward; the expression of connexin 43 and gap junction functionality were decreased, whereas the expression of claudin-11 was increased. CBZ enhanced the Sertoli cell number and decreased germ cells on day 21. The most striking effect of low doses of CBZ was a dose-dependent reduction of the round spermatid (RS) number, at every day of culture, associated to an increase in TP1 and TP2 mRNAs, specific of RSs. ERα and ERβ mRNAs were either increased or decreased depending of the CBZ concentration. The absence of testosterone in the culture medium resulted in a relative greater increase of TP1 and TP2 mRNAs by CBZ on day 21 versus controls. Hence, low doses of CBZ do possess an endocrine-disrupting effect on spermatogenesis by regulating the levels of Erα and Erβ mRNAs and the mRNAs of the androgen-dependent RS-specific genes, TP1 and TP2.
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