Testis

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

Abstract
The process of spermatogenesis requires a delicate balance of pro- and anti-apoptotic signaling to maintain optimal sperm output. A major transcription factor known to regulate numerous apoptosis related genes is NF-B. Here we show that mono-(2-ethylhexyl) phthalate (MEHP, 1g/kg) induces translocation of NF-B subunits (p65, p50 and c-Rel) to germ cell nuclei in young rats (postnatal day 28) as early as one hour 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-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 hours after MEHP exposure. These results suggest that NF-B is involved in the testicular response to MEHP induced injury.

Key words: Testis • Toxicology • Apoptosis • Spermatogenesis

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