Extracellular Matrix Functions in Follicle Maturation

Berkholtz, Courtney B.; Shea, Lonnie D.; Woodruff, Teresa K.

doi:10.1055/s-2006-948555

Cited by 119 publications

(87 citation statements)

References 69 publications

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“…Previous works by others have shown that extracellular matrices such as Matrigel can have beneficial effects on ovarian follicle culture, granulosa cell communication, proliferation, survival, and steroidogenesis in vitro in various species [24]. We first studied the differentiation of SSCs into ovarian-cell-like cells in the presence of Matrigel.…”

Section: Resultsmentioning

confidence: 99%

Ovarian-Cell-Like Cells from Skin Stem Cells Restored Estradiol Production and Estrus Cycling in Ovariectomized Mice

Park

Pan²,

Toms³

et al. 2014

Stem Cells and Development

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Reduction of estradiol production and high serum concentrations of follicular stimulating hormone (FSH) are endocrine disorders associated with premature ovarian failure. Here, we report that transplantation of ovarianlike cells differentiated from stem cells restored endogenous serum estradiol levels. Stem cells were isolated from postnatal mouse skin and differentiated into ovarian-cell-like cells that are consistent with female germ, and ovarian follicle somatic cells. The ovarian-cell-like cells were transplanted into ovariectomized mice (Cell Trans), whereas control mice were subjected to bilateral ovariectomies without cell transplantation (OVX). Using vaginal cytology analysis, it was revealed that in 13 out of 19 Cell Trans mice, estrus cycles were restored around 8 weeks after cell transplantation and were maintained until 16 weeks post-transplantation, whereas in the OVX group, all mice were arrested at metestrus/diestrus of the estrus cycle. The uterine weight in the Cell Trans group was similar to sham operation mice (Sham OP), while severe uterine atrophy and a decreased uterine weight were observed in the OVX group. Histologically, ectopic follicle-like structures and blood vessels were found within and around the transplants. At 12-14 weeks after cell transplantation, mean serum estradiol level in Cell Trans mice (178.0 -35 pg/mL) was comparable to that of the Sham OP group (188.9 -29 pg/mL), whereas it was lower in the OVX group (59.0 -4 pg/mL). Serum FSH concentration increased in the OVX group (1.62 -0.32 ng/mL) compared with the Sham OP group (0.39 -0.34 ng/mL). Cell Trans mice had a similar FSH level (0.94 -0.23 ng/mL; P < 0.05) to Sham OP mice. Our results suggest that ovarian somatic cells differentiated from stem cells are functional in vivo. In addition to providing insights into the function of ovarian somatic cells derived from stem cells, our study may offer potential therapeutic means for patients with hypo-estradiol levels like those encountered in premature ovarian failure.

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Section: Resultsmentioning

confidence: 99%

Ovarian-Cell-Like Cells from Skin Stem Cells Restored Estradiol Production and Estrus Cycling in Ovariectomized Mice

Park

Pan²,

Toms³

et al. 2014

Stem Cells and Development

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“…However, even in the presence of LIF, these cells cultured in monolayers gradually lose their functional characteristics such as production of cytochrome P450-aromatase and FSHR. Similarly, during spontaneous luteinization of GCs in vitro, the initially globular GCs progressively lose their ability to express not only aromatase and FSHR but also type IV collagen (Coll IV) (6), the principal component of the extracellular matrix (ECM) (7,8).…”

Section: Introductionmentioning

confidence: 99%

A Novel Three-Dimensional Culture System Allows Prolonged Culture of Functional Human Granulosa Cells and Mimics the Ovarian Environment

Kossowska-Tomaszczuk

Pelczar

Güven

et al. 2010

Tissue Engineering Part A

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A novel three-dimensional culture system allows prolonged culture of functional human granulosa cells and mimics the ovarian environment AbstractThe development of techniques allowing the growth of primordial follicles to mature follicles in vitro has much potential for both reproductive medicine and developmental research. However, human primordial and preantral follicles fail to grow after isolation from the surrounding ovarian stroma. Granulosa cells (GCs), which normally undergo apoptosis after ovulation, contain a subpopulation of ovarian follicular cells remaining viable in vitro over prolonged time periods when cultured in the presence of leukaemia inhibiting factor (LIF). However, when cultured as monolayers, they progressively lose all their characteristics, such as follicle-stimulating hormone receptor (FSHR) and cytochrome P450-aromatase. Here, we describe a three-dimensional (3D) culture system containing type I collagen, which, together with LIF, allowed the survival and growth of a subpopulation of GCs isolated from mature ovarian follicles and supported them to proliferate into spherical structures exhibiting steroidogenic capacity, as demonstrated by P450-aromatase and 3-hydroxysteroid dehydrogenase. After transplantation into the ovaries of immuno-deficient mice, these cells became localized preferentially within antral follicles and the prolonged expression of FSHR was confirmed as well. With this optimization of the culture conditions an environment was created, which acts as a niche closely mimicking the development of early ovarian follicles in vitro. ENVIRONMENT (doi: 10.1089 This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof. 2 ABSTRACTThe development of techniques allowing the growth of primordial follicles to mature follicles in vitro has much potential for both reproductive medicine and developmental research. However, human primordial and preantral follicles fail to grow after isolation from the surrounding ovarian stroma.Granulosa cells (GCs), which normally undergo apoptosis after ovulation, contain a subpopulation of ovarian follicular cells remaining viable in vitro over prolonged time periods when cultured in the presence of leukaemia inhibiting factor (LIF). However, when cultured as monolayers, they progressively lose all their characteristics, such as follicle-stimulating hormone receptor (FSHR) and cytochrome P450-aromatase. Here, we describe a three-dimensional (3D) culture system containing type I collagen, which, together with LIF, allowed the survival and growth of a subpopulation of GCs isolated from mature ovarian follicles and supported them to proliferate into spherical structures exhibiting steroidogenic capacity, as demonstrated by P450-aromatase and 3β-hydroxysteroid dehydrogenase. After transplantation into the ovaries of immuno-deficient mice, these cells became localized preferentially within antral follicles and the prolonged expressi...

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“…The basal lamina excludes blood vessels and nerves from the GCoocyte unit until after ovulation and, unlike the zona pellucida, is not traversed by any cells or cell processes (Rodgers et al, 2003). In a wide variety of tissues, basal laminae provide support and anchorage for polarised epithelial cells and also regulate their behaviour (cell shape, proliferation, apoptosis, differentiation and migration) (Berkholtz et al, 2006b;Monniaux et al, 2006). A direct transmembrane link between the ECM and the actin cytoskeleton is provided by integrins, which are expressed in the ovary and have a significant role in the regulation of cell behaviour in a wide range of tissues Monniaux et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Effect of cell shape and packing density on granulosa cell proliferation and formation of multiple layers during early follicle development in the ovary

Silva-Buttkus

Jayasooriya

Mora

et al. 2008

Journal of Cell Science

106

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The postnatal mouse ovary is rich in quiescent and early-growing oocytes, each one surrounded by a layer of somatic granulosa cells (GCs) on a basal lamina. As oocytes start to grow the GCs change shape from flattened to cuboidal, increase their proliferation and form multiple layers, providing a unique model for studying the relationship between cell shape, proliferation and multilayering within the context of two different intercommunicating cell types: somatic and germ cells. Proliferation of GCs was quantified using immunohistochemistry for Ki67 and demonstrated that, unusually, cuboidal cells divided more than flat cells. As a second layer of GCs started to appear, cells on the basal lamina reached maximum packing density and the axes of their mitoses became perpendicular to the basal lamina, resulting in cells dividing inwards to form second and subsequent layers. Proliferation of basal GCs was less than that of inner cells. Ultrastructurally, collagen fibrils outside the basal lamina became more numerous as follicles developed. We propose that the basement membrane and/or theca cells that surround the follicle provide an important confinement for rapidly dividing columnar cells so that they attain maximum packing density, which restricts lateral mitosis and promotes inwardly oriented cell divisions and subsequent multilayering.

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Extracellular Matrix Functions in Follicle Maturation

Cited by 119 publications

References 69 publications

Ovarian-Cell-Like Cells from Skin Stem Cells Restored Estradiol Production and Estrus Cycling in Ovariectomized Mice

Ovarian-Cell-Like Cells from Skin Stem Cells Restored Estradiol Production and Estrus Cycling in Ovariectomized Mice

A Novel Three-Dimensional Culture System Allows Prolonged Culture of Functional Human Granulosa Cells and Mimics the Ovarian Environment

Effect of cell shape and packing density on granulosa cell proliferation and formation of multiple layers during early follicle development in the ovary

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