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First published online December 12, 2006
doi: 10.1242/10.1242/dev.02667

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Infertility caused by retardation of follicular development in mice with oocyte-specific expression of Foxo3a

Lian Liu^1,2,*, Singareddy Rajareddy^1,*, Pradeep Reddy^1,*, Chun Du¹, Krishna Jagarlamudi¹, Yan Shen¹, David Gunnarsson³, Gunnar Selstam³, Karin Boman⁴ and Kui Liu^1,

¹ Department of Medical Biochemistry and Biophysics, Umeå University, SE-90187, Umeå, Sweden.
² Qilu Hospital, Shandong University, Jinan, 250012, Shandong, China.
³ Department of Molecular Biology and Umeå University, SE-90187, Umeå, Sweden.
⁴ Department of Radiation Sciences, Umeå University, SE-90187, Umeå, Sweden.

Author for correspondence (e-mail: kui.liu{at}medchem.umu.se)

Accepted 29 September 2006

In recent years, mammalian oocytes have been proposed to have important roles in the orchestration of ovarian follicular development and fertility. To determine whether intra-oocyte Foxo3a, a component of the phosphatidylinositol 3-kinase (PI3K) signaling pathway, influences follicular development and female fertility, a transgenic mouse model was generated with constitutively active Foxo3a expressed in oocytes. We found that the female transgenic mice were infertile, which was caused by retarded oocyte growth and follicular development, and anovulation. Further mechanistic studies revealed that the constitutively active Foxo3a in oocytes caused a dramatic reduction in the expression of bone morphogenic protein 15 (Bmp15), connexin 37 and connexin 43, which are important molecules for the establishment of paracrine and gap junction communications in follicles. Foxo3a was also found to facilitate the nuclear localization of p27^kip1 in oocytes, a cyclin-dependent kinase (Cdk) inhibitor that may serve to inhibit oocyte growth. The results from the current study indicate that Foxo3a is an important intra-oocyte signaling molecule that negatively regulates oocyte growth and follicular development. Our study may therefore give some insight into oocyte-borne genetic aberrations that cause defects in follicular development and anovulation in human diseases, such as premature ovarian failure.

Key words: Oocyte, Foxo3a, PI3K pathway, Follicular development, Transgenic, Mouse

Related articles in Development:

Foxa3: support signal from oocyte to follicle

Development 2007 134: e105. [Full Text]  

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