Constitutively active Foxo3 in oocytes preserves ovarian reserve in mice

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 fin...

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Bibliographic Details
Published in:Nature communications Vol. 4; no. 1; p. 1843
Main Authors: Pelosi, Emanuele, Omari, Shakib, Michel, Marc, Ding, Jun, Amano, Tomokazu, Forabosco, Antonino, Schlessinger, David, Ottolenghi, Chris
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 2013
Nature Publishing Group
Subjects:
631/443/494
692/698/1460/1527/1710
Aging
Animals
Female
Females
Fertility
Follicle Stimulating Hormone - blood
Forkhead Box Protein O3
Forkhead Transcription Factors - metabolism
Gene Expression Profiling
Gene Expression Regulation, Developmental
Humanities and Social Sciences
Humans
Luteinizing Hormone - blood
Menopause
Mice
Mice, Knockout
multidisciplinary
Oligonucleotide Array Sequence Analysis
Oocytes - cytology
Oocytes - metabolism
Ovarian Follicle - growth & development
Ovarian Follicle - metabolism
Ovary - cytology
Ovary - metabolism
Science
Transgenes
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary: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. The number of primordial follicles, which constitute the ovarian reserve, decreases with age. By overexpressing a constitutively active version of the transcription factor FOXO3, the authors increase the ovarian reserve and fertility in aging female mice.
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ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms2861