NF-kappaB 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-kappaB. Here we show that mono-(2-ethylhexyl) phthalate (MEHP, 1 g/kg) induces translocation of NF-kappaB 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-kappaB-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-kappaB is involved in the testicular response to MEHP-induced injury.
Rasoulpour
Reza J
RJ
Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island 02912, USA.
Boekelheide
Kim
K
D000818:Animals; D017209:Apoptosis; D003720:Densitometry; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D024202:Electrophoretic Mobility Shift Assay; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D013737:Testis / Q000187:drug effects* / Q000378:metabolism*
D016328:NF-kappa B; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate