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journal article Feb 01, 2008

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

Pradeep Reddy Lian Liu ORCID Deepak Adhikari ORCID Krishna Jagarlamudi Singareddy Rajareddy Yan Shen ORCID Chun Du ORCID Wenli Tang ORCID Tuula Hämäläinen Stanford L. Peng ORCID Zi-Jian Lan Austin J. Cooney Ilpo Huhtaniemi Kui Liu ORCID
Science Vol. 319 No. 5863 pp. 611-613 · American Association for the Advancement of Science (AAAS)
View at Publisher Save 10.1126/science.1152257
Abstract
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.
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References
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Supported by the J. C. Kempe and Seth M. Kempe Memorial Foundation the Swedish Research Council the Swedish Cancer Foundation Lion's Cancer Research Foundation at Umeå University and the Novo Nordisk Foundation (K.L.).
Cited By
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Metrics
724
Citations
12
References
Details
Published
Feb 01, 2008
Vol/Issue
319(5863)
Pages
611-613
Authors
P
Pradeep Reddy

Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.; Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan 250012, China.; Department of Physiology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.; Clinical Research and Exploratory Development, Roche Palo Alto, Palo Alto, CA 94304, USA.; Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA.

L
Lian Liu

Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.; Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan 250012, China.; Department of Physiology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.; Clinical Research and Exploratory Development, Roche Palo Alto, Palo Alto, CA 94304, USA.; Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA.

D
Deepak Adhikari

Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.; Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan 250012, China.; Department of Physiology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.; Clinical Research and Exploratory Development, Roche Palo Alto, Palo Alto, CA 94304, USA.; Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA.

K
Krishna Jagarlamudi

Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.; Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan 250012, China.; Department of Physiology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.; Clinical Research and Exploratory Development, Roche Palo Alto, Palo Alto, CA 94304, USA.; Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA.

S
Singareddy Rajareddy

Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.; Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan 250012, China.; Department of Physiology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.; Clinical Research and Exploratory Development, Roche Palo Alto, Palo Alto, CA 94304, USA.; Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA.

Y
Yan Shen

Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.; Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan 250012, China.; Department of Physiology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.; Clinical Research and Exploratory Development, Roche Palo Alto, Palo Alto, CA 94304, USA.; Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA.

C
Chun Du

Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.; Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan 250012, China.; Department of Physiology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.; Clinical Research and Exploratory Development, Roche Palo Alto, Palo Alto, CA 94304, USA.; Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA.

W
Wenli Tang

Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.; Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan 250012, China.; Department of Physiology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.; Clinical Research and Exploratory Development, Roche Palo Alto, Palo Alto, CA 94304, USA.; Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA.

T
Tuula Hämäläinen

Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.; Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan 250012, China.; Department of Physiology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.; Clinical Research and Exploratory Development, Roche Palo Alto, Palo Alto, CA 94304, USA.; Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA.

S
Stanford L. Peng

Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.; Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan 250012, China.; Department of Physiology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.; Clinical Research and Exploratory Development, Roche Palo Alto, Palo Alto, CA 94304, USA.; Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA.

Z
Zi-Jian Lan

Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.; Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan 250012, China.; Department of Physiology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.; Clinical Research and Exploratory Development, Roche Palo Alto, Palo Alto, CA 94304, USA.; Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA.

A
Austin J. Cooney

Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.; Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan 250012, China.; Department of Physiology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.; Clinical Research and Exploratory Development, Roche Palo Alto, Palo Alto, CA 94304, USA.; Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA.

I
Ilpo Huhtaniemi

Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.; Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan 250012, China.; Department of Physiology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.; Clinical Research and Exploratory Development, Roche Palo Alto, Palo Alto, CA 94304, USA.; Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA.

K
Kui Liu

Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.; Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan 250012, China.; Department of Physiology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.; Clinical Research and Exploratory Development, Roche Palo Alto, Palo Alto, CA 94304, USA.; Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA.

Cite This Article
Pradeep Reddy, Lian Liu, Deepak Adhikari, et al. (2008). Oocyte-Specific Deletion of Pten Causes Premature Activation of the Primordial Follicle Pool. Science, 319(5863), 611-613. https://doi.org/10.1126/science.1152257
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