Regulation of the proliferative activity of ovarian surface epithelial cells by follicular fluid

Doyle, L.K.; Donadeu, F.X.

doi:10.1016/j.anireprosci.2008.10.012

Cited by 6 publications

(6 citation statements)

References 28 publications

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“…High proliferation rates in the OSE following culture with insulin or IGF were observed as described in previous studies [3,24,25]; however, by utilizing a 3D organ culture system, the present study demonstrates that high levels of insulin and IGF induce hyperplasia and formation of multiple cell layers in the OSE. Treatment of organ cultures with the IR/IGF1R inhibitor tyrphostin AG1024 restored the OSE to a single layer of epithelium and reduced proliferation to basal rates.…”

Section: Introductionsupporting

confidence: 80%

“…Physiological concentrations in the ovary range from 0.5-10 ng/mL insulin and 100-500 ng/mL IGF [40]. Previously IGF1 at 100 ng/mL was reported to increase OSE proliferation [3,41]. The signaling pathway primarily responsible for this hyperplasia was the PI3K pathway, as inclusion of the PI3K inhibitor LY294002 restored growth of the OSE to a single cell layer (Figure 6).…”

Section: Discussionmentioning

confidence: 99%

“…Following oocyte extrusion, the OSE proliferates to heal the wound in the surface of the ovary [2]. OSE have receptors for steroid hormones and growth factors, both of which are found in abundance in follicular fluid released during ovulation [3]. In particular, the OSE has been shown to express insulin receptor (IR) and insulin-like growth factor receptors (IGF1Rs); additionally, at high concentrations insulin can signal through IGF1R or through hybrid receptors of IR and IGF1R [4,5].…”

Section: Introductionmentioning

confidence: 99%

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Insulin and insulin-like growth factor signaling increases proliferation and hyperplasia of the ovarian surface epithelium and decreases follicular integrity through upregulation of the PI3-kinase pathway

et al. 2013

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BackgroundThe ovarian surface epithelium responds to cytokines and hormonal cues to initiate proliferation and migration following ovulation. Although insulin and IGF are potent proliferative factors for the ovarian surface epithelium and IGF is required for follicle development, increased insulin and IGF activity are correlated with at least two gynecologic conditions: polycystic ovary syndrome and epithelial ovarian cancer. Although insulin and IGF are often components of in vitro culture media, little is known about the effects that these growth factors may have on the ovarian surface epithelium morphology or how signaling in the ovarian surface may affect follicular health and development.MethodsOvaries from CD1 mice were cultured in alginate hydrogels in the presence or absence of 5 μg/ml insulin or IGF-I, as well as small molecule inhibitors of IR/IGF1R, PI 3-kinase signaling, or MAPK signaling. Tissues were analyzed by immunohistochemistry for expression of cytokeratin 8 to mark the ovarian surface epithelium, Müllerian inhibiting substance to mark secondary follicles, and BrdU incorporation to assess proliferation. Changes in gene expression in the ovarian surface epithelium in response to insulin or IGF-I were analyzed by transcription array. Extracellular matrix organization was evaluated by expression and localization of collagen IV.ResultsCulture of ovarian organoids with insulin or IGF-I resulted in formation of hyperplastic OSE approximately 4–6 cell layers thick with a high rate of proliferation, as well as decreased MIS expression in secondary follicles. Inhibition of the MAPK pathway restored MIS expression reduced by insulin but only partially restored normal OSE growth and morphology. Inhibition of the PI 3-kinase pathway restored MIS expression reduced by IGF-I and restored OSE growth to a single cell layer. Insulin and IGF-I altered organization of collagen IV, which was restored by inhibition of PI 3-kinase signaling.ConclusionsWhile insulin and IGF are often required for propagation of primary cells, these cytokines may act as potent mitogens to disrupt cell growth, resulting in formation of hyperplastic OSE and decreased follicular integrity as measured by MIS expression and collagen deposition. This may be due partly to altered collagen IV deposition and organization in the ovary in response to insulin and IGF signaling mediated by PI 3-kinase.

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Section: Introductionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Insulin and insulin-like growth factor signaling increases proliferation and hyperplasia of the ovarian surface epithelium and decreases follicular integrity through upregulation of the PI3-kinase pathway

et al. 2013

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“…The OSE cell cultures including oocyte-like cells depleted/converted these hormones from the culture medium. It has already been found that follicular fluid can induce OSE cell proliferation, but estradiol and progesterone did not induce the cell proliferation; it was concluded that follicular fluid directly stimulates OSE cell proliferation by nonsteroidal mitogens [35]. On the other hand several studies confirmed that estradiol has a positive impact on the human oocyte growth and maturation in vivo and in vitro .…”

Section: Discussionmentioning

confidence: 99%

Expression of Pluripotency and Oocyte-Related Genes in Single Putative Stem Cells from Human Adult Ovarian Surface Epithelium CulturedIn Vitroin the Presence of Follicular Fluid

Virant‐Klun

Skutella²,

Kubista³

et al. 2013

BioMed Research International

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The aim of this study was to trigger the expression of genes related to oocytes in putative ovarian stem cells scraped from the ovarian surface epithelium of women with premature ovarian failure and cultured in vitro in the presence of follicular fluid, rich in substances for oocyte growth and maturation. Ovarian surface epithelium was scraped and cell cultures were set up by scrapings in five women with nonfunctional ovaries and with no naturally present mature follicles or oocytes. In the presence of donated follicular fluid putative stem cells grew and developed into primitive oocyte-like cells. A detailed single-cell gene expression profiling was performed to elucidate their genetic status in comparison to human embryonic stem cells, oocytes, and somatic fibroblasts. The ovarian cell cultures depleted/converted reproductive hormones from the culture medium. Estradiol alone or together with other substances may be involved in development of these primitive oocyte-like cells. The majority of primitive oocyte-like cells was mononuclear and expressed several genes related to pluripotency and oocytes, including genes related to meiosis, although they did not express some important oocyte-specific genes. Our work reveals the presence of putative stem cells in the ovarian surface epithelium of women with premature ovarian failure.

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“…The TGFB1 concentration in the samples was 1.3-4.8 ng/ml, which falls within the range found in human follicular fluid [17]. Based on the volume of follicular fluid obtained (1-2 ml) and dilutions of follicular fluid previously reported in the literature [18], the samples were diluted 1:10 in MOSE medium.…”

Section: Follicular Fluid and Cytokinesmentioning

confidence: 99%

The Mouse Ovarian Surface Epithelium Contains a Population of LY6A (SCA-1) Expressing Progenitor Cells That Are Regulated by Ovulation-Associated Factors1

Gamwell

Collins

Vanderhyden

2012

Biology of Reproduction

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The ovarian surface epithelium, a single layer of poorly differentiated epithelial cells, covers the surface of the ovary and is ruptured during ovulation. Little is known about the changes that occur in this layer before or during ovulation, and even less is known about the regenerative processes that occur after the surface is ruptured to release a mature oocyte. Recently, a population of mouse ovarian surface epithelial (MOSE) cells that exhibit progenitor/stem cell characteristics has been identified, though neither a genetic marker nor how these cells are regulated has been determined. We have identified a defined population of MOSE cells with progenitor cell characteristics that express the stem cell marker lymphocyte antigen 6 complex, locus A (LY6A; also known as stem cell antigen-1 [SCA-1]). By testing the effect of factors found in the follicular fluid at ovulation on proliferation, sphere formation, and LY6A expression, we have determined that the size of the LY6A-expressing (LY6A+) progenitor cell population is regulated by at least two ovulation-associated factors present in the follicular fluid: transforming growth factor beta 1 and leukemia-inhibitory factor. Our work has identified a population of LY6A+ MOSE progenitor cells on the surface of the ovary that may play a role in ovulatory wound healing.

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Regulation of the proliferative activity of ovarian surface epithelial cells by follicular fluid

Cited by 6 publications

References 28 publications

Insulin and insulin-like growth factor signaling increases proliferation and hyperplasia of the ovarian surface epithelium and decreases follicular integrity through upregulation of the PI3-kinase pathway

Insulin and insulin-like growth factor signaling increases proliferation and hyperplasia of the ovarian surface epithelium and decreases follicular integrity through upregulation of the PI3-kinase pathway

Expression of Pluripotency and Oocyte-Related Genes in Single Putative Stem Cells from Human Adult Ovarian Surface Epithelium CulturedIn Vitroin the Presence of Follicular Fluid

The Mouse Ovarian Surface Epithelium Contains a Population of LY6A (SCA-1) Expressing Progenitor Cells That Are Regulated by Ovulation-Associated Factors1

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