The transcription factor GATA4 is required for follicular development and normal ovarian function

Efimenko, Evgeni; Padua, Maria B.; Manuylov, Nikolay L.; Fox, Shawna C.; Morse, Deborah; Tevosian, Sergei G.

doi:10.1016/j.ydbio.2013.06.004

Cited by 59 publications

(54 citation statements)

References 66 publications

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“…Consistent with this expression pattern, different genetic mouse models have begun to illuminate the complex and essential roles played by this transcription factor in the very first steps of gonadal development and later, for male and female fertility (Kyrönlahti et al 2011a,b, Manuylov et al 2011, Bennett et al 2012, Efimenko et al 2013, Hu et al 2013, Tevosian 2014. While these studies clearly established the essential nature of GATA4 in reproduction, understanding how GATA4 accomplishes these tasks, i.e., identifying its target genes and thus its mechanism of action, remains incomplete.…”

Section: Discussionmentioning

confidence: 99%

“…These crucial functions in early mammalian gonadogenesis necessitate not only GATA4 but also a functional cooperation between GATA4 and its transcriptional partner Friend of GATA 2 (FOG2/ZFPM2; Tevosian et al 2002, Manuylov et al 2008. The requirement for GATA4 protein in testis and ovary is maintained during later fetal development and into adulthood, as several different groups have reported that loss of GATA4 at these stages is associated with disrupted cord formation and impaired spermatogenesis in the testis (Kyrö nlahti et al 2011a, Manuylov et al 2011, and impaired granulosa cell proliferation, theca cell recruitment, and a failure of follicular development ultimately leading to reduced fertility in the adult female (Kyrö nlahti et al 2011b, Bennett et al 2012, Efimenko et al 2013.…”

Section: Introductionmentioning

confidence: 99%

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GATA4 knockdown in MA-10 Leydig cells identifies multiple target genes in the steroidogenic pathway

Bergeron¹,

Nadeau²,

Viger³

2015

Reproduction

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GATA4 is an essential transcription factor required for the initiation of genital ridge formation, for normal testicular and ovarian differentiation at the time of sex determination, and for male and female fertility in adulthood. In spite of its crucial roles, the genes and/or gene networks that are ultimately regulated by GATA4 in gonadal tissues remain to be fully understood. This is particularly true for the steroidogenic lineages such as Leydig cells of the testis where many in vitro (promoter) studies have provided good circumstantial evidence that GATA4 is a key regulator of Leydig cell gene expression and steroidogenesis, but formal proof is still lacking. We therefore performed a microarray screening analysis of MA-10 Leydig cells in which Gata4 expression was knocked down using an siRNA strategy. Analysis identified several GATA4-regulated pathways including cholesterol synthesis, cholesterol transport, and especially steroidogenesis. A decrease in GATA4 protein was associated with decreased expression of steroidogenic genes previously suspected to be GATA4 targets such as Cyp11a1 and Star. Gata4 knockdown also led to an important decrease in other novel steroidogenic targets including Srd5a1, Gsta3, Hsd3b1, and Hsd3b6, as well as genes known to participate in cholesterol metabolism such as Scarb1, Ldlr, Soat1, Scap, and Cyp51. Consistent with the decreased expression of these genes, a reduction in GATA4 protein compromised the ability of MA-10 cells to produce steroids both basally and under hormone stimulation. These data therefore provide strong evidence that GATA4 is an essential transcription factor that sits atop of the Leydig cell steroidogenic program.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

GATA4 knockdown in MA-10 Leydig cells identifies multiple target genes in the steroidogenic pathway

Bergeron¹,

Nadeau²,

Viger³

2015

Reproduction

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“…At embryonic day (E) E10.5-E11.5, Gata4 is already expressed in the somatic cells of the developing genital ridges (Defalco et al 2011, Buganim et al 2012. At E13.5, Gata4 expression becomes sexually dimorphic; in the testis, expression is notably upregulated in Sertoli cells and reduced to some extent in interstitial cells, whereas strong-to-moderate GATA4 expression is observed in the majority of ovarian somatic cells (Heikinheimo et al 1997, Viger et al 1998, Anttonen et al 2003, Manuylov et al 2008, Efimenko et al 2013. A similar pattern of Gata4 expression has been reported in rats (Lavoie et al 2004).…”

Section: Expression Of Gata Genes In Reproductive Organsmentioning

confidence: 99%

“…i) Sf1Cre-mediated loss of Gata4 Efimenko et al (2013) used Sf1Cre-mediated gene targeting to determine the requirement for GATA4 and FOG2 in ovarian development and folliculogenesis. The results from this study identified an essential role for the GATA4 (but not FOG2) in the ovarian morphogenetic/differentiation program.…”

Section: Gata Proteins In Ovarian Developmentmentioning

confidence: 99%

Transgenic mouse models in the study of reproduction: insights into GATA protein function

Tevosian

2014

Reproduction

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For the past 2 decades, transgenic technology in mice has allowed for an unprecedented insight into the transcriptional control of reproductive development and function. The key factor among the mouse genetic tools that made this rapid advance possible is a conditional transgenic approach, a particularly versatile method of creating gene deletions and substitutions in the mouse genome. A centerpiece of this strategy is an enzyme, Cre recombinase, which is expressed from defined DNA regulatory elements that are active in the tissue of choice. The regulatory DNA element (either genetically engineered or natural) assures Cre expression only in predetermined cell types, leading to the guided deletion of genetically modified (flanked by loxP or 'floxed' by loxP) gene loci. This review summarizes and compares the studies in which genes encoding GATA family transcription factors were targeted either globally or by Cre recombinases active in the somatic cells of ovaries and testes. The conditional gene loss experiments require detailed knowledge of the spatial and temporal expression of Cre activity, and the challenges in interpreting the outcomes are highlighted. These studies also expose the complexity of GATA-dependent regulation of gonadal gene expression and suggest that gene function is highly context dependent.Reproduction (2014) 148 R1-R14

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“…The depletion of the follicular pool in a GATA-4 deficient ovary results in the formation of ovarian cysts and sterility [6].…”

Section: Introductionmentioning

confidence: 99%

Expression of Membrane Fusion Related Genes in Mouse Ovary

Jung

Sung

Park

2016

Korean J Clin Lab Sci.

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Granulosa cells surround the oocyte within the ovarian follicle and play an essential role in creating conditions required for oocyte as well as follicular development. The current study was conducted to examine the gene expression profile of mouse ovaries during the primordial to primary follicle transition process. Total RNAs from mouse ovaries on day 5 and day 12 were synthesized cDNA using annealing control primers. The DEGs were cloned and their identities were analyzed by BLAST search. The Plekha5 and Anxa11 were highly expressed in primary follicle stage. By contrast, their expression was increased in granulosa cells at the primary follicle stage. We have successfully discovered a list of genes expressed in day 5 and day 12 ovaries and confirmed that some of them are differentially expressed in PMF and/or PRI. This is a spatial-temporal regulatory mechanism on the ovarian folliculogenesis through membrane fusion. The gene expression profile from the current study would provide insight for future study on the mechanism(s) involved in primordial-primary follicular transition. This will provide information for identification of the mechanism of ovarian dysfunction.

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The transcription factor GATA4 is required for follicular development and normal ovarian function

Cited by 59 publications

References 66 publications

GATA4 knockdown in MA-10 Leydig cells identifies multiple target genes in the steroidogenic pathway

GATA4 knockdown in MA-10 Leydig cells identifies multiple target genes in the steroidogenic pathway

Transgenic mouse models in the study of reproduction: insights into GATA protein function

Expression of Membrane Fusion Related Genes in Mouse Ovary

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