Abstract
4-tert-octylphenol (OP) is known to disrupt testicular development and reduce male fertility. In the present study, male mice were exposed to OP at two different developmental stages, and the expression of steroidogenic enzymes and testosterone production were evaluated. Juvenile (15-day-old) and adult (8-week-old) male mice were injected with 2, 20, or 200 mg/kg of OP or 0.2 microg/kg of estradiol valerate for 5 days. Testosterone concentration was measured by radioimmunoassay and the expressions of the testicular genes were determined by RT-PCR analysis and immunohistochemistry. In the animals exposed with 20 mg/kg of OP during juvenile stage, histochemical analysis of the testis showed that number of pyknotic germ cells inside the tubule was increased, while the number of oil red O positive Leydig cells was decreased. Moreover, the lumen formation was remarkably delayed. A reduced serum testosterone concentration and down-regulated expressions of the mRNAs for steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (P450scc), and 17alpha-hydroxylase/C(17-20) lyase (P450(17alpha)) were also observed after juvenile exposure to OP. Immunohistochemical staining for P450scc was mainly detected in interstitial Leydig cells, and a slightly reduced expression of P450scc protein was observed in the testis exposed to 20 mg/kg of OP during juvenile stage. The present study demonstrates that juvenile exposure to OP inhibits steroidogenesis by decreasing the expressions of steroidogenic enzymes in the testis. Diminished lipid content in Leydig cells and reduced transcriptional expression of the cholesterol transport gene, StAR, also support altered cholesterol metabolism and/or transport as a potential mechanism for the decreased testosterone production following exposure to OP. Altogether, the alteration of steroidogenesis by exposure to OP may adversely affect the normal development of the testis and spermatogenesis.
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