Abstract
BACKGROUND: Early-life exposure to exogenous estrogens such as phytoestrogens (plant-derived estrogens) could affect later health through epigenetic modifications. Foeniculum vulgare (fennel) and Linum usitatissimum (flax) are two common medicinal plants with high phytoestrogen content. Considering the developmental epigenetic programming effect of phytoestrogens, the main goal of the present study was to evaluate the perinatal exposure with life-long exposure to hydroalcoholic extracts of both plants on offspring's ovarian epigenetic changes and estrogen receptors (ESRs) expression level as signaling cascades triggers of phytoestrogens. METHODS: Pregnant mice were randomly divided into control (CTL) that received no treatment and extract-treated groups that received 500 mg/kg/day of fennel (FV) and flaxseed (FX) alone or in combination (FV + FX) during gestation and lactation. At weaning, female offspring exposed to extracts prenatally remained on the maternal-doses diets until puberty. Then, the ovaries were collected for morphometric studies and quantitative real-time PCR analysis. RESULTS: A reduction in mRNA transcripts of the epigenetic modifying enzymes DNMTs and HDACs as well as estrogen receptors was observed in the FV and FX groups compared to the CTL group. Interestingly, an increase in ESRα/ESRβ ratio along with HDAC2 overexpression was observed in the FV + FX group. CONCLUSION: Our findings clearly show a positive relationship between pre and postnatal exposure to fennel and flaxseed extracts, ovarian epigenetic changes, and estrogen receptors expression, which may affect the estrogen signaling pathway. However, due to the high phytoestrogen contents of these extracts, the use of these plants in humans requires more detailed investigations.