| Title: | Targeted disruption of Pten in ovarian granulosa cells enhances ovulation and extends the life span of luteal cells |
| Author(s): | Fan HY; Liu Z; Cahill N; Richards JS; |
| Address: | "Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA" |
| ISSN/ISBN: | 0888-8809 (Print) 0888-8809 (Linking) |
| Abstract: | "FSH activates the phosphatidylinositol-3 kinase (PI3K)/acute transforming retrovirus thymoma protein kinase pathway and thereby enhances granulosa cell differentiation in culture. To identify the physiological role of the PI3K pathway in vivo we disrupted the PI3K suppressor, Pten, in developing ovarian follicles. To selectively disrupt Pten expression in granulosa cells, Ptenfl/fl mice were mated with transgenic mice expressing cAMP response element recombinase driven by Cyp19 promoter (Cyp19-Cre). The resultant Pten mutant mice were fertile, ovulated more oocytes, and produced moderately more pups than control mice. These physiological differences in the Pten mutant mice were associated with hyperactivation of the PI3K/acute transforming retrovirus thymoma protein kinase pathway, decreased susceptibility to apoptosis, and increased proliferation of mutant granulosa cells. Strikingly, corpora lutea of the Pten mutant mice persisted longer than those of control mice. Although the follicular and luteal cell steroidogenesis in Ptenfl/fl;Cyp19-Cre mice was similar to controls, viable nonsteroidogenic luteal cells escaped structural luteolysis. These findings provide the novel evidence that Pten impacts the survival/life span of granulosa/luteal cells and that its loss not only results in the facilitated ovulation but also in the persistence of nonsteroidogenic luteal structures in the adult mouse ovary" |
| Keywords: | Animals Apoptosis/genetics/physiology Cell Proliferation Cellular Senescence/genetics/physiology Corpus Luteum Maintenance/genetics/physiology Estradiol/blood Female Granulosa Cells/*cytology/*physiology Litter Size/genetics/physiology Luteal Cells/*cytol; |
| Notes: | "MedlineFan, Heng-Yu Liu, Zhilin Cahill, Nicola Richards, JoAnne S eng HD07165/HD/NICHD NIH HHS/ R56 HD016229/HD/NICHD NIH HHS/ T32 HD007495/HD/NICHD NIH HHS/ U54 HD007495/HD/NICHD NIH HHS/ HD16272/HD/NICHD NIH HHS/ R01 HD016272/HD/NICHD NIH HHS/ R01 HD016229/HD/NICHD NIH HHS/ P30 HD007495/HD/NICHD NIH HHS/ T32 HD007165/HD/NICHD NIH HHS/ HD-16229/HD/NICHD NIH HHS/ HD07495/HD/NICHD NIH HHS/ R37 HD016229/HD/NICHD NIH HHS/ Research Support, N.I.H., Extramural 2008/07/09 Mol Endocrinol. 2008 Sep; 22(9):2128-40. doi: 10.1210/me.2008-0095. Epub 2008 Jul 7" |
