Paradoxical Action of Activin A on Folliculogenesis in Immature and Adult Mice

Yokota, Hiromi; Yamada, Kiyohiko; Liu, Xiaowei; Kobayashi, Junro; Abe, Yumiko; Mizunuma, Hideki; Ibuki, Yoshito

doi:10.1210/endo.138.11.5526

Cited by 54 publications

(23 citation statements)

References 27 publications

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“…In line with this, we could show that premature follicles, lacking a thecal shell, fail to induce angiogenesis, even when transplanted into ovariectomized animals which regularly exhibit elevated FSH levels (Bex & Goldman 1975). The present observation of lack of vascular growth of the preantral follicles is thus compatible with previous reports that FSH is not able to stimulate morphological changes in the granulosa cell-oocyte complexes (Li et al 1995, Yokota et al 1997.…”

Section: Follicular Angiogenesissupporting

confidence: 92%

Ovariectomy improves neovascularization and microcirculation of freely transplanted ovarian follicles

Laschke

Menger²,

Vollmar³

2002

Journal of Endocrinology

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To investigate the influence of ovariectomy on the physiological process of neovascularization of ovarian follicles, we harvested follicles with a theca interna at 48 h after pregnant mare's serum gonadotropin (PMSG) treatment of Syrian golden hamsters, for subsequent transplantation onto striated muscle tissue of chronically implanted skinfold chambers of non-ovariectomized PMSGsynchronized hamsters and bilaterally ovariectomized hamsters. Non-ovariectomized non-PMSG-treated animals served as controls. During a 2 week period after transplantation, neovascularization of these freely transplanted grafts was quantified in vivo by assessment of the newly developed microvascular follicular network, its microvessel density, the diameter of microvessels and their volumetric blood flow using fluorescence microscopic techniques. At day 3 after transplantation, capillary sprouts could be observed in all groups studied, finally developing a complete glomerulum-like microvascular network within 5-10 days. In ovariectomized animals, however, vascularization of follicular tissue was found to be accelerated and enhanced when compared with the follicles in both groups of non-ovariectomized animals. This was associated with significantly higher capillary blood perfusion, which may in part represent the graft's adaptive response to pro-angiogenic stimuli due to elevated gonadotropin levels, but might in particular be mediated by gonadotropin-induced release of vasoactive substances. Interestingly, small preantral follicles lacking a theca interna failed to vascularize in either of the groups. In conclusion, the study demonstrates that ovariectomy improves neovascularization and microcirculation of freely transplanted ovarian follicles.

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Section: Follicular Angiogenesissupporting

confidence: 92%

Ovariectomy improves neovascularization and microcirculation of freely transplanted ovarian follicles

Laschke

Menger²,

Vollmar³

2002

Journal of Endocrinology

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“…Other possible candidates are the bone morphogenetic proteins BMP-4 and -7, which are first detected at the primary and secondary stages respectively (18) and stimulate initiation of follicle growth (27,28). Activin is a further candidate; although it has been shown to be an inhibitor of preantral follicle development in adult mice (13), the same group and others have demonstrated stimulatory effects in prepubertal animals (29,30). Alternatively, growing follicles may produce an antagonist to the inhibitor produced by primordial follicles, resulting in the stimulation of growth of other nearby follicles.…”

Section: Discussionmentioning

confidence: 99%

Inferring biological mechanisms from spatial analysis: Prediction of a local inhibitor in the ovary

Silva-Buttkus

Marcelli

Franks

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Female mammals are born with a lifetime's supply of oocytes individually enveloped in flattened epithelial cells to form primordial follicles. It is not clear how sufficient primordial follicles are maintained to sustain the reproductive lifespan, while providing an adequate supply of mature oocytes for ovulation. Locally produced growth factors are thought to be critical regulators of early follicle growth, but knowledge of their identity and source remains incomplete. Here, we have used a simple approach of spatial analysis of structures in histological tissue sections to identify likely sources of such regulatory molecules, narrowing the field for future screening for candidate growth factors or antagonists. We have quantified the relative spatial positions of primordial (resting) follicles and growing follicles in mice on days 4, 8, and 12 after birth, and calculated interfollicular distances. Follicles were significantly less likely to have started growing if they had 1 or more primordial follicles close by (within 10 m), predicting that primordial follicles inhibit each other. This approach allows us to hypothesize that primordial follicles produce a diffusible inhibitor that prevents neighboring primordial follicles from growing. Such an approach has wide applicability within many branches of developmental and cell biology for studying spatial signaling within tissues and cells.diffusing inhibitor ͉ follicle growth ͉ signal gradient

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“…Follistatin, on the other hand, modulates the function of granulosa cells in favour of luteinization or atresia by neutralizing the actions of activin and may also directly modulate progesterone metabolism by granulosa cells (Findlay, 1993;Li et al, 1995;Miro and Hillier, 1996). However, the stimulatory action of activin on the proliferation of granulosa cells may be stage-specific (Yokota et al, 1997;Liu et al, 1998;Mizunuma et al, 1999). Activin A has no effect on preantral follicles from adult mice and blocks FSHstimulated follicular growth, although activin A enhances preantral follicular growth in immature mice (Yokota et al, 1997).…”

Section: Interaction With Activinsmentioning

confidence: 99%

“…However, the stimulatory action of activin on the proliferation of granulosa cells may be stage-specific (Yokota et al, 1997;Liu et al, 1998;Mizunuma et al, 1999). Activin A has no effect on preantral follicles from adult mice and blocks FSHstimulated follicular growth, although activin A enhances preantral follicular growth in immature mice (Yokota et al, 1997). In addition, these authors showed that in vitro activin, secreted by secondary follicles, causes primary follicles to become dormant at the resting stage, an action reversed by follistatin (Mizunuma et al, 1999).…”

Section: Interaction With Activinsmentioning

confidence: 99%

Regulation of ovarian function by the TGF-beta superfamily and follistatin

et al. 2003

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The role of follistatin as an activin-binding protein has dominated the study of this molecule for the last 10 years. However, there is emerging evidence that follistatin has a role in modulating the biology of other members of the transforming growth factor beta (TGF-beta) superfamily. This review summarizes the current concepts encompassing follistatin biochemistry as well as molecules with which it is functionally associated. Moreover, the importance of the two follistatin isoforms (follistatin-288 and follistatin-315) is discussed with particular emphasis on the regulation of the ovary. In addition to activin, this review discusses the functions of other members of the TGF-beta superfamily, for example growth differentiation factor 9 (GDF-9), bone morphogenetic protein 15 (BMP-15), BMP-6, BMP-4 and BMP-7, in the ovary, and the potential interactions between follistatin and these growth factors. The complex network of TGF-beta superfamily growth factor members involved in the modulation of ovarian function and the interactions of follistatin with these proteins is highlighted.

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Paradoxical Action of Activin A on Folliculogenesis in Immature and Adult Mice

Cited by 54 publications

References 27 publications

Ovariectomy improves neovascularization and microcirculation of freely transplanted ovarian follicles

Ovariectomy improves neovascularization and microcirculation of freely transplanted ovarian follicles

Inferring biological mechanisms from spatial analysis: Prediction of a local inhibitor in the ovary

Regulation of ovarian function by the TGF-beta superfamily and follistatin

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