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Pisarska M.D.,Center for Fertility and Reproductive Medicine | Pisarska M.D.,University of California at Los Angeles | Kuo F.-T.,Center for Fertility and Reproductive Medicine | Bentsi-Barnes I.K.,Center for Fertility and Reproductive Medicine | And 2 more authors.
American Journal of Physiology - Endocrinology and Metabolism | Year: 2010

Forkhead L2 (FOXL2) is expressed in the ovary and acts as a transcriptional repressor of the steroidogenic acute regulatory (StAR) gene, a marker of granulosa cell differentiation. Human FOXL2 mutations that produce truncated proteins lacking the COOH terminus result in blepharophimosis/ptosis/epicanthus inversus (BPES) syndrome type I, which is associated with premature ovarian failure (POF). In this study, we investigated whether FOXL2's activity as a transcriptional repressor is regulated by phosphorylation. We found that FOXL2 is phosphorylated at a serine residue and, using yeast two-hybrid screening, identified LATS1 as a potential FOXL2-interacting protein. LATS1 is a serine/threonine kinase whose deletion in mice results in an ovarian phenotype similar to POF. Using coimmunoprecipitation and kinase assays, we confirmed that LATS1 binds to FOXL2 and demonstrated that LATS1 phosphorylates FOXL2 at a serine residue. Moreover, we found that FOXL2 and LATS1 are coexpressed in developing mouse gonads and in granulosa cells of small and medium follicles in the mouse ovary. Last, we demonstrated that coexpression with LATS1 enhances FOXL2's activity as a repressor of the StAR promoter, and this results from the kinase activity of LATS1. These results provide novel evidence that FOXL2 is phosphorylated by LATS1 and that this phosphorylation enhances the transcriptional repression of the StAR gene, a marker of granulosa cell differentiation. These data support our hypothesis that phosphorylation of FOXL2 may be a control mechanism regulating the rate of granulosa cell differentiation and hence, follicle maturation, and its dysregulation may contribute to accelerated follicular development and POF in BPES type I. Copyright © 2010 the American Physiological Society.


Wang E.T.,Cedars Sinai Medical Center | Wang E.T.,University of California at Los Angeles | Pisarska M.D.,Cedars Sinai Medical Center | Pisarska M.D.,Center for Fertility and Reproductive Medicine
Contemporary Ob/Gyn | Year: 2013

Fertility preservation in reproductive-age women with cancer remains an important but under-represented topic. Specific fertility preservation strategies exist for women facing gynecologic surgery, pelvic radiation, and/or chemotherapy. Recent advances in the field of ART have made oocyte cryopreservation, in addition to embryo cryopreservation, an established and accepted option. Optimization of investigational methods such as IVM and ovarian tissue cryopreservation is the goal of researchers in this field in order to better meet the needs of all women with cancer. © 2014 Advanstar Communications, Inc. All rights reserved.

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