Inactivation of Retinoblastoma Protein (Rb1) in the Oocyte: Evidence That Dysregulated Follicle Growth Drives Ovarian Teratoma Formation in Mice
Ovarian teratomas (OTs) are the most frequent germ cell tumors in adult women, but their origin and molecular etiology remains poorly defined. We found that conditional deletion of the tumor suppressor Rb1 in the oocyte leads to OT development in young adult female mice. Further analysis revealed disturbances in both recruitment and growth of follicles. Although oocytes from mutants did not exhibit an enhanced propensity for parthenogenetic activation–a proposed source of OTs–premature meiotic resumption was evident in oocytes of immature follicles. These findings, together with data from previous studies, suggest that a defect in oocyte-somatic cell communication leading to an uncoupling of coordinated growth and ultimately impaired sustainment of meiotic arrest is sufficient to drive OT development.
Vyšlo v časopise:
Inactivation of Retinoblastoma Protein (Rb1) in the Oocyte: Evidence That Dysregulated Follicle Growth Drives Ovarian Teratoma Formation in Mice. PLoS Genet 11(7): e32767. doi:10.1371/journal.pgen.1005355
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1005355
Souhrn
Ovarian teratomas (OTs) are the most frequent germ cell tumors in adult women, but their origin and molecular etiology remains poorly defined. We found that conditional deletion of the tumor suppressor Rb1 in the oocyte leads to OT development in young adult female mice. Further analysis revealed disturbances in both recruitment and growth of follicles. Although oocytes from mutants did not exhibit an enhanced propensity for parthenogenetic activation–a proposed source of OTs–premature meiotic resumption was evident in oocytes of immature follicles. These findings, together with data from previous studies, suggest that a defect in oocyte-somatic cell communication leading to an uncoupling of coordinated growth and ultimately impaired sustainment of meiotic arrest is sufficient to drive OT development.
Zdroje
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Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
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