Protective effect of resveratrol on urogenital sinus and prostate development in rats exposed in utero to TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin)

Abstract

This study evaluated the protective effects of resveratrol on the prostate development of rats exposed to TCDD. Pregnant rats received TCDD (1 μg/kg) at GD15 and/or RES (20 mg/kg/day) from GD10 to PND21. Newborn and adult males from Control, TCDD, TCDD + RES and RES groups were euthanized and the prostate was excised. On PND1, there was a reduction in the number of prostatic buds, AR-positive mesenchymal cells and proliferation index in epithelial and mesenchymal cells in TCDD group, but restored by RES. AhR immunoreactivity was greater in TCDD group than the other groups. On PND90, there was higher frequency of functional hyperplasia in the distal area of the prostate acini in TCDD group, but restored by RES. AhRR expression was higher in the TCDD while NRF2 was higher in the TCDD + RES compared to the other groups. Resveratrol was able to reduce the adverse effects of TCDD on prostate development and its long-term repercussions.

Animal Toxicology Studies on the Male Reproductive Effects of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin: Data Analysis and Health Effects Evaluation

“…The systematic literature search was performed using the PECO statement and generated 3246 studies after finding duplication. After screening, a total of 55 studies ( 12 – 15 , 19 – 21 , 23 – 70 ) passed the inclusion criteria for data extraction. The literature selection process is displayed as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow chart ( Figure 1 ) .…”

“…TCDD exposure may result in numerous male reproductive toxic effects, such as spermatogenesis retardance and low testicular and sex organ weight ( 13 ). According to studies focusing on its toxicological mechanisms, TCDD is believed to exert its effects by binding to an intracellular transcription factor known as aryl hydrocarbon receptor (AhR) with high affinity ( 15 ). The treatment of wild-type rats with TCDD during pregnancy may result in gonadotropins and testicular steroid synthesis disorders in their offspring, but AhR knockout rats are not sensitive to this treatment ( 70 ).…”

“…Recent studies found that resveratrol can rescue the toxic effects caused by TCDD to some extent. TCDD administration induces the reduction in the number of prostatic buds, which may cause prostate dysplasia, whereas this adverse effect is not significantly observed when TCDD is taken with resveratrol simultaneously ( 15 ). The reduction in Sertoli cell numbers and abnormal seminiferous tubule numbers caused by TCDD exposure can be protected by resveratrol ( 14 ).…”

“…The gestational exposure of TCDD is reported to decrease the body weight of male offspring, but a 30year cohort study found no significant association between male offspring birthweight changes and in utero TCDD exposure (16)(17)(18). A dosage of 0.7 µg/kg TCDD exposure on gestational day 15 reduces the anogenital distance (AGD) of male offspring on postnatal days 1 and 4, whereas 1 µg/kg TCDD exposure on gestational day 15 shows no apparent effect on male AGD on postnatal day 1 in another study (15,19). The oral dosage of 1 µg/kg TCDD is reported to induce low testes weight, but these results are still inconsistent with other studies (20,21).…”

“…The potential adverse effects of TCDD on males have been investigated by human epidemiological studies and nonhuman animal studies (6,(12)(13)(14)(15)(16). The gestational exposure of TCDD is reported to decrease the body weight of male offspring, but a 30year cohort study found no significant association between male offspring birthweight changes and in utero TCDD exposure (16)(17)(18).…”