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Publication : Constitutively active Foxo3 in oocytes preserves ovarian reserve in mice.

First Author  Pelosi E Year  2013
Journal  Nat Commun Volume  4
Pages  1843 PubMed ID  23673628
Mgi Jnum  J:318965 Mgi Id  MGI:6862129
Doi  10.1038/ncomms2861 Citation  Pelosi E, et al. (2013) Constitutively active Foxo3 in oocytes preserves ovarian reserve in mice. Nat Commun 4:1843
abstractText  During female reproductive life, ovarian follicle reserve is reduced by maturation and atresia until menopause ensues. Foxo3 is required to maintain the ovarian reserve in mice. Here we show that overexpression of constitutively active FOXO3 can increase ovarian reproductive capacity in mice. We find increased follicle numbers and decreased gonadotropin levels in aging FOXO3-transgenic mice compared with wild-type littermates, suggesting maintenance of a greater ovarian reserve. Based on cumulative progeny in aging animals, we find 31-49% increased fertility in transgenic females. The gene expression profile of Foxo3-/- knockout ovaries appears older than that of wild-type littermates, and the transgene induces a younger-looking profile, restoring much of the wild-type transcriptome. This is the first gain-of-function model of augmented reproductive reserve in mice, thus emphasizing the role of Foxo3 as a guardian of the ovarian follicle pool in mammals and a potential determinant of the onset of menopause.
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