Reproduction Abstracts

Introduction: Women with mutations in BRCA1 gene have an increased lifetime risk of ovarian cancer. Many studies but not all have shown that an adequate folate intake is protective against many cancers including ovarian, but recent studies have shown that high levels of folic acid (FA) supplementation can promote cancer risk. The aim of this study is to determine FA impact on the expression of cancer related genes in the ovary such as OCT4 a pluripotency factor, BRCA1 related to DNA repair and the chromatin modifying enzyme EZH2.

Methods: Juvenile (4 wks old) or adult (10 wks old) female C57BL/6 mice were fed for 4 weeks with normal (1 mg/Kg), high (5 mg/Kg) or supramaximal (20 mg/kg) doses of FA and then kept on maintenance diet until 4 or 12 weeks after supplementation. Quantitative RT-PCR was performed to determine the mRNA levels.

Results and Discussion: FA supplementation during the juvenile period led to an increase in Oct4, Brca1 and Ezh2 expression immediately after the treatment. However, those effects did not persist after the end of supplementation. In contrast, FA during adulthood led to an increase in Oct4, Brca1 and Ezh2, which persisted 4 weeks after the end of supplementation. These results show that FA affects the expression of cancer related genes in the ovary, but the effects are dependent on the dose and time of supplementation. Future work is needed to identify histological alterations on ovaries and if FA could modify the quality and/or quantity of ovarian follicles.