Foxo3 negatively regulates the activation of mouse primordial oocytes.

PURPOSE: The objective of this study is to know the role of Foxo3, a forkhead transcription factor, in the growth initiation of primordial oocytes in neonatal mice. METHODS: We studied the expression of Foxo3 in 0-, 1-, 2-, 7- and 21-day-old mouse ovaries by immunohistochemistry. Ovaries from 1-day-old mice were treated with Foxo3 siRNAs (small interfering RNAs) and subsequently organ-cultured for 6 days, and the oocyte growth was examined histologically. RESULTS: Expression of Foxo3 was low in newborn mouse ovaries. In 1-day-old ovaries, Foxo3 was expressed in the nuclei of 20 ± 7 % primordial oocytes. The percentage of Foxo3-positive primordial oocytes was increased to 48 ± 8, 37 ± 2 and 47 ± 4 in 2-, 7- and 21-day-old mice, respectively. After treatment of ovaries with Foxo3 siRNAs, higher proportion of oocytes entered the growth phase in cultured ovaries than that in control. CONCLUSIONS: These results suggest that Foxo3 negatively regulates the growth initiation of primordial oocytes and knockdown of Foxo3 leads primordial oocytes to the growth phase in vitro.