A role for estrogen in somatic cell fate of the mammalian gonad

Pask, Andrew J

doi:10.1007/s10577-011-9260-1

Cited by 18 publications

(15 citation statements)

References 59 publications

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“…The estrogen receptor signaling pathway is crucial to maintain granulosa cells in the mature gonad [56]. Moreover, estrogen signaling has a protumor activity based on two associated mechanisms: transcriptional repression of proapoptotic molecules, such as Bak1, and enhanced transcription of antiapoptotic factors, such as Bcl2 [57,58].…”

Section: Discussionmentioning

confidence: 99%

Soy Promotes Juvenile Granulosa Cell Tumor Development in Mice and in the Human Granulosa Cell Tumor-Derived COV434 Cell Line1

Mansouri-Attia

James

Ligon

et al. 2014

Biology of Reproduction

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Soy attracts attention for its health benefits, such as lowering cholesterol or preventing breast and colon cancer. Soybeans contain isoflavones, which act as phytoestrogens. Even though isoflavones have beneficial health effects, a role for isoflavones in the initiation and progression of diseases including cancer is becoming increasingly recognized. While data from rodent studies suggest that neonatal exposure to genistein (the predominant isoflavone in soy) disrupts normal reproductive function, its role in ovarian cancers, particularly granulosa cell tumors (GCT), is largely unknown. Our study aimed to define the contribution of a soy diet in GCT development using a genetically modified mouse model for juvenile GCTs (JGCT; Smad1 Smad5 conditional double knockout mice) as well as a human JGCT cell line (COV434). While dietary soy cannot initiate JGCT development in mice, we show that it has dramatic effects on GCT growth and tumor progression compared to a soy-free diet. Loss of Smad1 and Smad5 alters estrogen receptor alpha (Esr1) expression in granulosa cells, perhaps sensitizing the cells to the effects of genistein. In addition, we found that genistein modulates estrogen receptor expression in the human JGCT cell line and positively promotes cell growth in part by suppressing caspase-dependent apoptosis. Combined, our work suggests that dietary soy consumption has deleterious effects on GCT development.

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Section: Discussionmentioning

confidence: 99%

Soy Promotes Juvenile Granulosa Cell Tumor Development in Mice and in the Human Granulosa Cell Tumor-Derived COV434 Cell Line1

Mansouri-Attia

James

Ligon

et al. 2014

Biology of Reproduction

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“…In the absence of the estrogen-producing enzyme aromatase (or Cyp19) or receptors for estrogen (estrogen receptor α and β), granulosa cells transdifferentiate into Sertoli cells in the adult ovary, yet early ovarian differentiation appears normal [Couse and Korach, 1999;Britt et al, 2001;Britt and Findlay, 2003]. In marsupials and some non-mammalian species, estrogen signaling prevents translocation of SOX9 into the nucleus, therefore blocking the initiation of testis differentiation [for a review see Pask, 2012]. In the adult mouse ovary, FOXL2 acts in conjunction with ERα as a direct transcriptional repressor of the testis pathway by binding to the regulatory sequence of Sox9 [Uhlenhaut et al, 2009].…”

Section: Molecular Pathways That Drive Ovarian Differentiation and Mamentioning

confidence: 99%

Building an Ovary: Insights into Establishment of Somatic Cell Lineages in the Mouse

Nicol

Yao²

2014

Sex Dev

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The molecular pathways that drive the differentiation of somatic cell populations in the testis and ovary have been the subjects of intensive research over the past decade. It is now clear that ovarian differentiation is a coordinate event driven by secreted factors including R-spondin1, WNT4, and follistatin and transcriptional regulators such as β-catenin and FOXL2. These factors direct bipotential somatic cell lineages toward an ovarian fate and simultaneously suppress the emergence of testis-determining processes. This review summarizes the molecular pathways responsible for establishment of the ovary and discusses the current hypotheses on the origin(s) of somatic cell lineages and how these somatic cells acquire the characteristics necessary for their function during ovarian development and maintenance.

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“…The Sertoli cells orchestrate further differentiation of other cell types within the forming testis [Berta et al, 1990;Koopman et al, 1991;Capel, 2000]. In females, the absence of the Y chromosome leads to the induction of an ovarian-specific pathway including WNT4 and CTNNB1 [Eggers and Sinclair, 2012], and the presence of estrogen maintains the ovarian cells' fate [Pask, 2012]. The formation of a normal gonad ensures the production of hormones needed to drive the sexual differentiation of other embryonic dimorphic structures like the GT, urogenital sinus, Wolffian/Müllerian duct, and brain [Wilhelm and Koopman, 2006].…”

Section: Hormonal Control Of the Sexually Dimorphic External Genitaliamentioning

confidence: 99%

Development of the External Genitalia and Their Sexual Dimorphic Regulation in Mice

Ipulan¹,

Suzuki²,

Matsushita³

et al. 2014

Sex Dev

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The study of the external genitalia is divided into 2 developmental stages: the formation and growth of a bipotential genital tubercle (GT) and the sexual differentiation of the male and female GT. The sexually dimorphic processes, which occur during the second part of GT differentiation, are suggested to be governed by androgen signaling and more recently crosstalk with other signaling factors. The process of elucidating the regulatory mechanisms of hormone signaling towards other signaling networks in the GT is still in its early stages. Nevertheless, it is becoming a productive area of research. This review summarizes various studies on the development of the murine GT and the defining characteristics of a masculinized GT and presents the different signaling pathways possibly involved during masculinization.

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A role for estrogen in somatic cell fate of the mammalian gonad

Cited by 18 publications

References 59 publications

Soy Promotes Juvenile Granulosa Cell Tumor Development in Mice and in the Human Granulosa Cell Tumor-Derived COV434 Cell Line1

Soy Promotes Juvenile Granulosa Cell Tumor Development in Mice and in the Human Granulosa Cell Tumor-Derived COV434 Cell Line1

Building an Ovary: Insights into Establishment of Somatic Cell Lineages in the Mouse

Development of the External Genitalia and Their Sexual Dimorphic Regulation in Mice

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