Maternal Resveratrol Treatment Reduces the Risk of Mammary Carcinogenesis in Female Offspring Prenatally Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) presents adverse effects on breast development/carcinogenesis. This study aimed to identify the ability of resveratrol (Res) to modify the adverse effects of TCDD in a female offspring. Pregnant female Wistar rats were allocated into four groups: TCDD, TCDD + Res, Res, and control. TCDD (1 μg/kg) was orally administered as a single dose on gestational day (GD) 15, and Res was orally administered during GD10-21 and lactation at a dose of 20 mg/kg/day. Female offsprings were euthanized on a specific postnatal day (PND) for hormonal analysis (PND 22, 48-51), vaginal opening (PND 30-48), and mammary gland morphology (PND 22). Other females received two doses of N-nitroso-N-methylurea (MNU, 50 mg/kg) on PNDs 22 and 51 and were euthanized on PND 24 (Ki-67, ER-α and apoptosis indexes or molecular analysis) or PND 180 (tumor assay). TCDD exposure altered the development of the mammary structure while these alterations were partially improved by maternal Res. Two days after first MNU administration, some genes associated with apoptosis were altered in the mammary tissue from the TCDD group (Bax and Caspase 3 down- and Bcl-2 upregulated) but were also partially reestablished by maternal Res. Mammary gland bcl-2 and bcl-xl proteins expression was increased while the apoptosis index was reduced by TCDD exposure but restored by maternal Res. An increase in number of mammary tumors was observed in female offspring from the TCDD group compared to the other groups. The results indicate that most mammary changes induced in female offspring through TCDD exposure or after MNU administrations were reduced by maternal resveratrol treatment.

Acquired Resilience: An Evolved System of Tissue Protection in Mammals

“…125 Work is beginning on the ability of resveratrol exposure to pregnant rats to improve the health of their offspring, for example, to reduce the susceptibility of offspring to toxin-induced carcinogenesis. 126 And the protection provided by resveratrol against cancer is being traced, for example, to its ability at low concentrations to stabilize spindle assemblies during mitotic division of normally mitotic cells. 127 The horizons of study of resveratrol, indeed of all the resilience-inducing interventions considered here, continue to broaden.…”

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

“…Although the effects of oxidative stress caused by TCDD in the prostate were not excessively harmful during the study period, other studies point to an increase in the susceptibility to breast carcinogenesis [54], alteration in the stereogenesis and in the antioxidant system of epididymal sperm [81]. Adittionally, further studies can be proposed for an evaluation of the effects of gestational exposure to TCDD in older adult animals and in models of prostatic carcinogenesis.…”

“…Thus, resveratrol is a polyphenolic compound with an AhR antagonist activity and that has anti-inflammatory, antioxidant and anti-cancer properties that might to inhibit TCDD adverse actions [49][50][51][52][53]. Some in vivo studies have shown that resveratrol can mitigate the toxic effects induced by in utero TCDD exposure in male and female reproductive organs, including reduction in breast cancer susceptibility [54][55][56].…”

Prevention and Co-Management of Breast Cancer-Related Osteoporosis Using Resveratrol

“…More interestingly, resveratrol is able to synergistically enhance the effect of aromatase inhibitors on hormone-sensitive BC cells by modulating aromatase activity at the epigenetic level, sustaining the hypothesis of its co-therapeutic benefits [ 177 ]. Further, resveratrol also appears to be a promising natural substance for the prevention of BC recurrence during pregnancy, without negative effects on the embryo [ 178 ]. Indeed, positive effects of resveratrol on embryogenesis and the prevention of BC during pregnancy and pregnancy complications as well as on improvements in reproductive health have been reported [ 179 , 180 ].…”