Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 1 February 2008:
Vol. 319. no. 5863, pp. 611 - 613
DOI: 10.1126/science.1152257
Prev | Table of Contents | Next

Reports

Oocyte-Specific Deletion of Pten Causes Premature Activation of the Primordial Follicle Pool

Pradeep Reddy,1 Lian Liu,1,2* Deepak Adhikari,1* Krishna Jagarlamudi,1* Singareddy Rajareddy,1* Yan Shen,1 Chun Du,1 Wenli Tang,1 Tuula Hämäläinen,3 Stanford L. Peng,4 Zi-Jian Lan,5 Austin J. Cooney,6 Ilpo Huhtaniemi,3,7 Kui Liu1{dagger}

In the mammalian ovary, progressive activation of primordial follicles from the dormant pool serves as the source of fertilizable ova. Menopause, or the end of female reproductive life, occurs when the primordial follicle pool is exhausted. However, the molecular mechanisms underlying follicle activation are poorly understood. We provide genetic evidence that in mice lacking PTEN (phosphatase and tensin homolog deleted on chromosome 10) in oocytes, a major negative regulator of phosphatidylinositol 3-kinase (PI3K), the entire primordial follicle pool becomes activated. Subsequently, all primordial follicles become depleted in early adulthood, causing premature ovarian failure (POF). Our results show that the mammalian oocyte serves as the headquarters of programming of follicle activation and that the oocyte PTEN-PI3K pathway governs follicle activation through control of initiation of oocyte growth.

1 Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.
2 Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan 250012, China.
3 Department of Physiology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.
4 Clinical Research and Exploratory Development, Roche Palo Alto, Palo Alto, CA 94304, USA.
5 Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA.
6 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
7 Department of Reproductive Biology, Imperial College London, Hammersmith Campus, London W12 0NN, UK.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: kui.liu{at}medchem.umu.se

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Inhibition of Vascular Endothelial Growth Factor Receptor Signal Transduction Blocks Follicle Progression but Does Not Necessarily Disrupt Vascular Development in Perinatal Rat Ovaries.
R. M. McFee, R. A. Artac, R. M. McFee, D. T. Clopton, R. A. L. Smith, T. G. Rozell, and A. S. Cupp (2009)
Biol Reprod 81, 966-977
   Abstract »    Full Text »    PDF »
Neutralization of Vascular Endothelial Growth Factor Antiangiogenic Isoforms Is More Effective Than Treatment with Proangiogenic Isoforms in Stimulating Vascular Development and Follicle Progression in the Perinatal Rat Ovary.
R. A. Artac, R. M. McFee, R. A. Longfellow Smith, M. M. Baltes-Breitwisch, D. T. Clopton, and A. S. Cupp (2009)
Biol Reprod 81, 978-988
   Abstract »    Full Text »    PDF »
The Mammalian Ovary from Genesis to Revelation.
M. A. Edson, A. K. Nagaraja, and M. M. Matzuk (2009)
Endocr. Rev. 30, 624-712
   Abstract »    Full Text »    PDF »
Do etiologies of premature ovarian aging (POA) mimic those of premature ovarian failure (POF)?.
N. Gleicher, A. Weghofer, K. Oktay, and D. Barad (2009)
Hum. Reprod. 24, 2395-2400
   Abstract »    Full Text »    PDF »
Molecular Mechanisms Underlying the Activation of Mammalian Primordial Follicles.
D. Adhikari and K. Liu (2009)
Endocr. Rev. 30, 438-464
   Abstract »    Full Text »    PDF »
PDK1 signaling in oocytes controls reproductive aging and lifespan by manipulating the survival of primordial follicles.
P. Reddy, D. Adhikari, W. Zheng, S. Liang, T. Hamalainen, V. Tohonen, W. Ogawa, T. Noda, S. Volarevic, I. Huhtaniemi, et al. (2009)
Hum. Mol. Genet. 18, 2813-2824
   Abstract »    Full Text »    PDF »
Prepubertal Primordial Follicle Loss in Mice Is Not Due to Classical Apoptotic Pathways.
C. M. Tingen, S. K. Bristol-Gould, S. E. Kiesewetter, J. T. Wellington, L. Shea, and T. K. Woodruff (2009)
Biol Reprod 81, 16-25
   Abstract »    Full Text »    PDF »
Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement.
E. Diamanti-Kandarakis, J.-P. Bourguignon, L. C. Giudice, R. Hauser, G. S. Prins, A. M. Soto, R. T. Zoeller, and A. C. Gore (2009)
Endocr. Rev. 30, 293-342
   Abstract »    Full Text »    PDF »
FSH and FOXO1 Regulate Genes in the Sterol/Steroid and Lipid Biosynthetic Pathways in Granulosa Cells.
Z. Liu, M. D. Rudd, I. Hernandez-Gonzalez, I. Gonzalez-Robayna, H.-Y. Fan, A. J. Zeleznik, and J. S. Richards (2009)
Mol. Endocrinol. 23, 649-661
   Abstract »    Full Text »    PDF »
PTEN, Stem Cells, and Cancer Stem Cells.
R. Hill and H. Wu (2009)
J. Biol. Chem. 284, 11755-11759
   Abstract »    Full Text »    PDF »
FoxO1 Mediates PTEN Suppression of Androgen Receptor N- and C-Terminal Interactions and Coactivator Recruitment.
Q. Ma, W. Fu, P. Li, S. V. Nicosia, G. Jenster, X. Zhang, and W. Bai (2009)
Mol. Endocrinol. 23, 213-225
   Abstract »    Full Text »    PDF »
Awakening the oocyte: controlling primordial follicle development.
E. A McLaughlin and S. C McIver (2009)
Reproduction 137, 1-11
   Abstract »    Full Text »    PDF »
The Current Status of Evidence for and Against Postnatal Oogenesis in Mammals: A Case of Ovarian Optimism Versus Pessimism?.
J. L. Tilly, Y. Niikura, and B. R. Rueda (2009)
Biol Reprod 80, 2-12
   Abstract »    Full Text »    PDF »
Oocyte-Specific Knockout: A Novel In Vivo Approach for Studying Gene Functions During Folliculogenesis, Oocyte Maturation, Fertilization, and Embryogenesis.
Q.-Y. Sun, K. Liu, and K. Kikuchi (2008)
Biol Reprod 79, 1014-1020
   Abstract »    Full Text »    PDF »
The Role of PLC{beta}1 in the Control of Oocyte Meiosis During Folliculogenesis.
A. Pesty, O. Broca, C. Poirot, and B. Lefevre (2008)
Reproductive Sciences 15, 661-672
   Abstract »    PDF »
Targeted Disruption of Pten in Ovarian Granulosa Cells Enhances Ovulation and Extends the Life Span of Luteal Cells.
H.-Y. Fan, Z. Liu, N. Cahill, and J. S. Richards (2008)
Mol. Endocrinol. 22, 2128-2140
   Abstract »    Full Text »    PDF »
Lysophospholipid signaling in the function and pathology of the reproductive system.
X. Ye (2008)
Hum. Reprod. Update 14, 519-536
   Abstract »    Full Text »    PDF »
Involvement of the KIT/KITL Signaling Pathway in 4-Vinylcyclohexene Diepoxide-Induced Ovarian Follicle Loss in Rats.
S. M. Fernandez, A. F. Keating, P. J. Christian, N. Sen, J. B. Hoying, H. L. Brooks, and P. B. Hoyer (2008)
Biol Reprod 79, 318-327
   Abstract »    Full Text »    PDF »
HABITS trial results confirmed in two-year follow-up.
S. Brown (2008)
Menopause Int 14, 48-51
   Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)