A Comparative Study on Transforming Growth Factor-β and Activin A for Preantral Follicles from Adult, Immature, and Diethylstilbestrol-Primed Immature Mice

Liu, Xiaowei; Andoh, Kazumichi; Abe, Yumiko; Kobayashi, Junro; Yamada, Kiyohiko; Mizunuma, Hideki; Ibuki, Yoshito

doi:10.1210/endo.140.6.6827

Cited by 51 publications

(2 citation statements)

References 26 publications

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“…Mouse preantral follicles secrete activin A (396), which stimulates granulosa cell proliferation and follicle growth when added to ovaries explanted from immature animals (233,240,396,496). Activin A induces granulosa cell proliferation and oocyte growth in bovine (276) trum-like structure and supports the maintenance of follicular morphology (276,484,496).…”

Section: Ovarymentioning

confidence: 99%

Activin A in Mammalian Physiology

Bloise

Ciarmela

Cruz

et al. 2019

Physiological Reviews

156

129

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Activins are dimeric glycoproteins belonging to the transforming growth factor beta superfamily and resulting from the assembly of two beta subunits, which may also be combined with alpha subunits to form inhibins. Activins were discovered in 1986 following the isolation of inhibins from porcine follicular fluid, and were characterized as ovarian hormones that stimulate follicle stimulating hormone (FSH) release by the pituitary gland. In particular, activin A was shown to be the isoform of greater physiological importance in humans. The current understanding of activin A surpasses the reproductive system and allows its classification as a hormone, a growth factor, and a cytokine. In more than 30 yr of intense research, activin A was localized in female and male reproductive organs but also in other organs and systems as diverse as the brain, liver, lung, bone, and gut. Moreover, its roles include embryonic differentiation, trophoblast invasion of the uterine wall in early pregnancy, and fetal/neonate brain protection in hypoxic conditions. It is now recognized that activin A overexpression may be either cytostatic or mitogenic, depending on the cell type, with important implications for tumor biology. Activin A also regulates bone formation and regeneration, enhances joint inflammation in rheumatoid arthritis, and triggers pathogenic mechanisms in the respiratory system. In this 30-yr review, we analyze the evidence for physiological roles of activin A and the potential use of activin agonists and antagonists as therapeutic agents.

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Section: Ovarymentioning

confidence: 99%

Activin A in Mammalian Physiology

Bloise

Ciarmela

Cruz

et al. 2019

Physiological Reviews

156

129

View full text Add to dashboard Cite

show abstract

“…Activins stimulate the proliferation of primordial germ cells and granulosa cells of early immature follicles (Li et al 1995;Miró and Hillier 1996;Yokota et al 1997;Liu et al 1999;El-Hefnawy and Zeleznik 2001;Bristol-Gould et al 2006). They also stimulate FSHR expression in granulosa cells (Hasegawa et al 1988;Xiao et al 1992;Nakamura et al 1993) and synergize with FSH to regulate the differentiation of granulosa cells during late folliculogenesis (Woodruff et al 1990;Findlay 1993;Kishi et al 1998).…”

Section: Discussionmentioning

confidence: 99%

Runx3 regulates folliculogenesis and steroidogenesis in granulosa cells of immature mice

et al. 2018

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We previously demonstrated that female Runx3 knockout (Runx3 −/−) mice were anovulatory and their uteri were atrophic, and that Runx3 mRNA was expressed in granulosa cells. To clarify how Runx3 regulates folliculogenesis and ovulation, we examined the effects of Runx3 knockout on the gene expression of growth factors associated with folliculogenesis and enzymes associated with steroidogenesis. In Runx3 −/− mouse ovaries, the numbers of primary and antral follicles were lower than those in wild type (wt) mice at 3 weeks of age, indicating that the loss of Runx3 affects folliculogenesis. The expression of genes encoding activin and inhibin subunits (Inha, Inhba, and Inhbb) was also decreased in ovaries from the Runx3 −/− mice compared with that in wt mice. Moreover, the expression of the genes Cyp11a1 and Cyp19a1 encoding steroidogenic enzymes was also decreased. In cultured granulosa cells from 3-week-old mouse ovaries, Cyp19a1 mRNA levels were lower in Runx3 −/− mice than those in wt mice. Follicle stimulating hormone (FSH) treatment increased Cyp19a1 mRNA levels in both wt and Runx3 −/− granulosa cells in culture, but the mRNA level in Runx3 −/− granulosa cells was lower than in wt ones, indicating that granulosa cells could not fully function in the absence of Runx3. At 3 weeks of age, gonadotropin α subunit, FSHβ subunit and Luteinizing hormone (LH)β subunit mRNA levels were decreased in Runx3 −/− mice. These findings suggest that Runx3 plays a key role in female reproduction by regulating folliculogenesis and steroidogenesis in granulosa cells.

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Transforming growth factor‐beta isoform expression during bovine ovarian antral follicle development

Nilsson

Doraiswamy

Skinner

2003

Molecular Reproduction Devel

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Transforming growth factor-beta (TGF-beta) isoforms are important paracrine and autocrine signaling molecules for the regulation of ovarian follicle growth and physiology. Effective communication between the epithelial granulosa cells, the mesenchymal theca cells, and the oocyte is vital for ovarian function and reproductive success. The expression, localization, and regulation of TGF-beta isoforms in the developing bovine follicle was examined using both immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (RT-PCR) procedures. TGF-beta1 protein was found to be present in the granulosa cells of early pre-antral, early antral, and 1-2 mm follicles. Interestingly, there was no visible staining of granulosa cells of 3-5 or 5-10 mm follicles. There was also no TGF-beta1 staining of theca cells. TGF-beta2 and TGF-beta3 staining were present in the granulosa and theca cells of all follicle stages examined. The levels of TGF-beta mRNA expression in granulosa and theca cells from antral follicles was measured using quantitative RT-PCR. For each isoform mRNA expression levels did not change in different sized antral follicles. TGF-beta3 mRNA levels were much higher than those of TGF-beta1 and TGF-beta2 in both granulosa and theca. Expression levels were higher in theca than in granulosa for TGF-beta2 and TGF-beta3. FSH was found to decrease TGF-beta1 mRNA expression in granulosa cells, but had no effect on TGF-beta2 and TGF-beta3. Bovine ovarian follicles were found to have a unique pattern of TGF-beta isoform expression and regulation when compared to other species (i.e., rodent, pig, quail, and human). The similarities and differences between the various species is discussed to help elucidate common functions of TGF-beta in the ovary. In summary, observations demonstrate that as antral follicles develop, TGF-beta3 is the most abundant TGF-beta isoform and TGF-beta1 protein levels decline in large follicles. Granulosa cell TGF-beta1 expression was decreased by FSH and this correlated with reduced levels in large antral follicles. TGF-betas involved in antral follicular growth and development appear to act as paracrine/autocrine signaling molecules having a species-specific pattern of expression.

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A Comparative Study on Transforming Growth Factor-β and Activin A for Preantral Follicles from Adult, Immature, and Diethylstilbestrol-Primed Immature Mice

Cited by 51 publications

References 26 publications

Activin A in Mammalian Physiology

Activin A in Mammalian Physiology

Runx3 regulates folliculogenesis and steroidogenesis in granulosa cells of immature mice

Transforming growth factor‐beta isoform expression during bovine ovarian antral follicle development

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