Abstract
The objective of the present study is to determine whether methoxychlor (MXC) exposure in adulthood affects rat Leydig cell regeneration and to compare its effects with estradiol (E2). Adult 90-day-old male Sprague-Dawley rats received ethane dimethane sulfonate (EDS) to eliminate the adult Leydig cell population. Subsequently, rats were randomly assigned to four groups and gavaged with corn oil (control), 0.25 mg/kg E2 and 10 or 100 mg/kg MXC daily from days 5 to 30 post-EDS treatment. The results showed that MXC and E2 reduced serum testosterone levels on day 58 post-EDS treatment. qPCR showed Hsd17b3 mRNA levels were downregulated 7–15 fold by E2 and MXC, indicating that development of the new population of Leydig cells was arrested at the earlier stage. This observation was supported by the results of histochemical staining, which demonstrated that Leydig cells in MXC-treated testis on day 58 post-EDS treatment were mostly progenitor Leydig cells. However, Pdgfb mRNA levels were downregulated, while Lif transcript levels were increased by MXC. In contrast, E2 did not affect gene expression for these growth factors. In conclusion, our findings indicated that both MXC and E2 delayed rat Leydig cell regeneration in the EDS-treated model, presumably acting by different mechanisms.
Highlights
Methoxychlor (MXC) is an organochlorine insecticide that is widely utilized in the agriculture sector [1,2,3,4]
The present study demonstrated that the exposure of adult rats to MXC during the critical window of days 5 to 30 post-ethane dimethane sulfonate (EDS) treatment resulted in the delayed maturation of Leydig cells, as assessed on day 58 post-EDS treatment
The levels of testicular Hsd17b3 mRNA in rats exposed to E2 and MXC on day 58 post-EDS treatment were similar to the control levels 32 days after EDS treatment, indicating that most Leydig cells remained at the progenitor or immature stages of development
Summary
Methoxychlor (MXC) is an organochlorine insecticide that is widely utilized in the agriculture sector [1,2,3,4]. Previous observations suggest that MXC is a reproductive toxicant, albeit with weak estrogenic activity [3], and its bioactive metabolite, 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), caused greater endocrine-disrupting toxicity in both sexes than the parent MXC compound [1,5]. Both MXC and HPTE inhibited androgen production by rat Leydig cells [1,5]. Several studies have shown that estradiol blocks the regeneration of the Leydig cell population in rats after treatment with the Leydig cell cytotoxin, ethane dimethane sulfonate (EDS) [7]. The results can provide a research basis for sexual dysfunction caused by pollutants
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call