Journal article
Inactivation of Retinoblastoma Protein (Rb1) in the Oocyte: Evidence That Dysregulated Follicle Growth Drives Ovarian Teratoma Formation in Mice
PLoS genetics, Vol.11(7), pp.e1005355-e1005355
07/2015
Handle:
https://hdl.handle.net/2376/110694
PMCID: PMC4503754
PMID: 26176933
Abstract
The origin of most ovarian tumors is undefined. Here, we report development of a novel mouse model in which conditional inactivation of the tumor suppressor gene Rb1 in oocytes leads to the formation of ovarian teratomas (OTs). While parthenogenetically activated ooctyes are a known source of OT in some mutant mouse models, enhanced parthenogenetic propensity in vitro was not observed for Rb1-deficient oocytes. Further analyses revealed that follicle recruitment and growth is disrupted in ovaries of mice with conditional inactivation of Rb1, leading to abnormal accumulation of secondary/preantral follicles. These findings underpin the concept that miscues between the germ cell and somatic compartments cause premature oocyte activation and the formation of OTs. Furthermore, these results suggest that defects in folliculogenesis and a permissive genetic background are sufficient to drive OT development, even in the absence of enhanced parthenogenetic activation. Thus, we have discovered a novel role of Rb1 in regulating the entry of primordial oocytes into the pool of growing follicles and signaling between the oocyte and granulosa cells during the protracted process of oocyte growth. Our findings, coupled with data from studies of other OT models, suggest that defects in the coordinated regulation between growth of the oocyte and somatic components in follicles are an underlying cause of OT formation.
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Details
- Title
- Inactivation of Retinoblastoma Protein (Rb1) in the Oocyte: Evidence That Dysregulated Follicle Growth Drives Ovarian Teratoma Formation in Mice
- Creators
- Qi-En Yang - Center for Reproductive Biology, School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, United States of AmericaSo I Nagaoka - Center for Reproductive Biology, School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, United States of AmericaIvy Gwost - Center for Reproductive Biology, School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, United States of AmericaPatricia A Hunt - Center for Reproductive Biology, School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, United States of AmericaJon M Oatley - Center for Reproductive Biology, School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, United States of America
- Publication Details
- PLoS genetics, Vol.11(7), pp.e1005355-e1005355
- Academic Unit
- Molecular Biosciences, School of
- Publisher
- United States
- Grant note
- R01 ES013527 / NIEHS NIH HHS T32 GM008336 / NIGMS NIH HHS ES013527 / NIEHS NIH HHS R56 ES013527 / NIEHS NIH HHS HD061665 / NICHD NIH HHS R01 HD061665 / NICHD NIH HHS
- Identifiers
- 99900547112601842
- Language
- English
- Resource Type
- Journal article