NF-(kappa)B Is Activated in the Rat Testis Following Exposure to Mono-(2-Ethylhexyl) Phthalate

The process of spermatogenesis requires a delicate balance of proapoptotic and antiapoptotic signaling to maintain optimal sperm output. A major transcription factor known to regulate numerous apoptosis-related genes is NF-(kappa)B. Here we show that mono-(2-ethylhexyl) phthalate (MEHP, 1 g/kg) induces translocation of NF-(kappa)B subunits (p65, p50, and c-Rel) to germ cell nuclei in young rats (Postnatal Day 28) as early as 1 h after exposure. Immunohistochemistry of rat testes exposed to MEHP showed increased p50 and c-Rel presence in spermatocytes and spermatogonia. In addition, there was increased p65 nuclear positivity in Sertoli cells and germ cells after MEHP, while Rel-B localization was unchanged. These alterations correlated with increased nuclear NF(kappa)B-binding activity after MEHP exposure, as shown by electrophoretic mobility shift assays of whole-testis nuclear protein extracts. The increased activity of this transcription factor was associated with a transient protection of the seminiferous epithelium manifested as a decreased number of germ cell apoptotic nuclei measured by TUNEL assay 6 h after MEHP exposure. These results suggest that NF-(kappa)B is involved in the testicular response to MEHP-induced injury.