The transcription factor FOXL2 in ovarian function and dysfunction.

Baere, Elfride De; Fellous, Marc; Veitia, Reiner A.

doi:10.2478/v10042-009-0062-7

Cited by 11 publications

(8 citation statements)

References 51 publications

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“…Although they serve 2 complementary and independent pathways, they cooperate in suppressing any male signals (mainly Sox9) [Nef and Vassalli, 2009;Schlessinger et al, 2010]. The role of Foxl2 in follicular development has been well characterized [De Baere et al, 2009]. Recently, it was shown that loss of Foxl2 function throughout life causes somatic reprogramming of the ovary, resulting in the gain of tes- [Uhlenhaut et al, 2009].…”

Section: Normal Gonadal Developmentmentioning

confidence: 99%

Gonadal Development and Tumor Formation at the Crossroads of Male and Female Sex Determination

Cools

Wolffenbuttel²,

Drop³

et al. 2011

Sex Dev

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Malignant germ cell tumor (GCT) formation is a well-known complication in the management of patients with a disorder of sex development (DSD). DSDs are defined as congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical. DSD patients in whom the karyotype – at least at the gonadal level – contains (a part of) the Y chromosome are at increased risk for neoplastic transformation of germ cells, leading to the development of the so-called ‘type II germ cell tumors’. However, tumor risk in the various forms of DSD varies considerably between the different diagnostic groups. This contribution integrates our actual knowledge on the pathophysiology of tumor development in DSDs, recent findings on gonadal (mal)development in DSD patients, and possible correlations between the patient’s phenotype and his/her risk for germ cell tumor development.

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Section: Normal Gonadal Developmentmentioning

confidence: 99%

Gonadal Development and Tumor Formation at the Crossroads of Male and Female Sex Determination

Cools

Wolffenbuttel²,

Drop³

et al. 2011

Sex Dev

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“…Within the ovary, FOXL2 has been shown to be essential for ovary development and function [8]. Germline FOXL2 mutations are present in blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) patients, an autosomal dominant condition characterized by defects in eyelid development with (type I) or without (type II) premature ovarian failure [1,9–16]. BPES FOXL2 mutations can induce cytoplasmic mislocalization as well as cytoplasmic or nuclear aggregation [15,17], which most likely contributes to altered function in some patients.…”

Section: Introductionmentioning

confidence: 99%

Granulosa cell tumor mutant FOXL2C134W suppresses GDF-9 and activin A-induced follistatin transcription in primary granulosa cells

McTavish¹,

Nonis²,

Hoang³

et al. 2013

Molecular and Cellular Endocrinology

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A single somatic FOXL2 mutation (FOXL2 C134W ) was identified in almost all granulosa cell tumor (GCT) patients. In the pituitary, FOXL2 and Smad3 coordinately regulate activin stimulation of follistatin transcription. We explored whether a similar regulation occurs in the ovary, and whether FOXL2 C134W has altered activity. We show that in primary granulosa cells, GDF-9 and activin increase Smad3-mediated follistatin transcription. In contrast to findings in the pituitary, FOXL2 negatively regulates GDF-9 and activin-stimulated follistatin transcription in the ovary. Knockdown of endogenous FOXL2 confirmed this inhibitory role. FOXL2 C134W displayed enhanced inhibitory activity, completely ablating GDF-9 and activin-induced follistatin transcription. GDF-9 and activin activity was lost when either the smad binding element or the forkhead binding element were mutated, indicating that both sites are required for Smad3 actions. This study highlights that FOXL2 negatively regulates follistatin expression within the ovary, and that the pathogenesis of FOXL2 C134W may involve an altered interaction with Smad3.

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“…It has an important role in follicular development (8,9,12,13). Recent investigations suggest a wider spectrum of tissues in which FOXL2 is expressed such as pituitary, macrophages, blood reticulocytes, hepatocytes, colon and heart (14). Infertility has a different range in affected females of type I (15,16).…”

Section: Introductionmentioning

confidence: 99%

Molecular Genetic Analysis of FOXL2 Gene in Two Iranian Families with Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome

et al. 2017

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Background: Blepharophimosis-ptosis-epicanthus syndrome (BPES) is a rare genetic disorder with autosomal dominant inheritance. There are two distinct phenotypes: BPES type I, which is associated with eyelid abnormalities as well as female infertility or premature menopause due to ovarian resistance to gonadotropins, whereas in type II only eyelid abnormalities are present. Mutations in the forkhead transcription factor 2 (FOXL2) gene are responsible for both types of BPES. Objectives: The purpose of this study was to identify mutations in FOXL2 in two Iranian families (from Tehran) with BPES who were referred to Tehran Medical Genetics laboratory. Methods: The peripheral blood was collected from the affected members of two BPES families and genomic DNA was extracted using salting out method. Then, direct sequencing of whole exon of FOXL2 genewas performed. Results: Two frameshift mutations were identified in FOXL2 gene in two familial cases including NM_023067:c.102_103insA (p.G35Rfs*61)as a novel mutation and NM_023067:c.855_871dup (p.H291Rfs*71) (17-bp insertion). Both mutations cause the protein to be truncated and are responsible for a severe phenotype (BPES type I) which was in harmony with our finding. Conclusions: Our results increased the spectrum of FOXL2 mutations and confirm the mutations associated with BPES type I.

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The transcription factor FOXL2 in ovarian function and dysfunction.

Cited by 11 publications

References 51 publications

Gonadal Development and Tumor Formation at the Crossroads of Male and Female Sex Determination

Gonadal Development and Tumor Formation at the Crossroads of Male and Female Sex Determination

Granulosa cell tumor mutant FOXL2C134W suppresses GDF-9 and activin A-induced follistatin transcription in primary granulosa cells

Molecular Genetic Analysis of FOXL2 Gene in Two Iranian Families with Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome

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