The Role of Fibroblast Growth Factor-18 in Follicular Atresia in Cattle1

Portela, Valério Marques; Dirandeh, E.; Guerrero-Netro, Hilda M; Zamberlam, Gustavo; Barreta, Marcos Henrique; Goetten, André Lucio Fontana; Price, Christopher A.

doi:10.1095/biolreprod.114.121376

Cited by 33 publications

(35 citation statements)

References 52 publications

(65 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…E 2 is a major determinant of follicle development and decreases granulosa cell apoptosis in rodents in vivo (Billig et al 1993). Studies with bovine granulosa cells have demonstrated that E 2 can overcome the apoptotic effect of ligands such as FASLG and FGF18 (Quirk et al 2006, Portela et al 2015. Of the main RSR pathways, MAPK3/1 is known to alter CYP19A1 mRNA levels; inhibition of MAPK3/1 phosphorylation increased CYP19A1 mRNA levels in bovine and rodent granulosa cells (Moore et al 2001, Silva et al 2006 and reduced the ability of tumor necrosis factor alpha to increase apoptosis (Morales et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Effects of the mycotoxin deoxynivalenol on steroidogenesis and apoptosis in granulosa cells

Guerrero-Netro¹,

Chorfi²,

Price³

2015

Reproduction

View full text Add to dashboard Cite

Mycotoxins can reduce fertility and development in livestock, notably in pigs and poultry, although the effect of most mycotoxins on reproductive function in cattle has not been established. One major mycotoxin, deoxynivalenol (DON), not only targets immune cells and activates the ribotoxic stress response (RSR) involving MAPK activation, but also inhibits oocyte maturation in pigs. In this study, we determined the effect of DON on bovine granulosa cell function using a serum-free culture system. Addition of DON inhibited estradiol and progesterone secretion, and reduced levels of mRNA encoding estrogenic (CYP19A1) but not progestogenic (CYP11A1 and STAR) proteins. Cell apoptosis was increased by DON, which also increased FASLG mRNA levels. The mechanism of action of DON was assessed by western blotting and PCR experiments. Addition of DON rapidly and transiently increased phosphorylation of MAPK3/1, and resulted in a more prolonged phosphorylation of MAPK14 (p38) and MAPK8 (JNK). Activation of these pathways by DON resulted in time-and dose-dependent increases in abundance of mRNA encoding the transcription factors FOS, FOSL1, EGR1, and EGR3. We conclude that DON is deleterious to granulosa cell function and acts through a RSR pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of the mycotoxin deoxynivalenol on steroidogenesis and apoptosis in granulosa cells

Guerrero-Netro¹,

Chorfi²,

Price³

2015

Reproduction

View full text Add to dashboard Cite

show abstract

“…Unlike the known actions of other FGFs in the ovary, however, FGF18 appears to be a proapoptotic factor. Abundance of FGF18 mRNA and protein is higher in atretic compared with growing bovine follicles, and addition of FGF18 increased the amount of DNA laddering and caspase-3 activation in granulosa cells in vitro (Portela et al 2010(Portela et al , 2015. The mechanisms of action of FGF18 in the follicle have not been fully elucidated, but it may act through a murine double minute 2 (MDM2) and p53 upregulated modulator of apoptosis (PUMA, also known as BBC3) pathway (Portela et al 2015), although it has not yet been shown whether FGF18 alters p53 signaling.…”

Section: The Role Of the Fgf8 Family In Follicle Developmentmentioning

confidence: 99%

“…Abundance of FGF18 mRNA and protein is higher in atretic compared with growing bovine follicles, and addition of FGF18 increased the amount of DNA laddering and caspase-3 activation in granulosa cells in vitro (Portela et al 2010(Portela et al , 2015. The mechanisms of action of FGF18 in the follicle have not been fully elucidated, but it may act through a murine double minute 2 (MDM2) and p53 upregulated modulator of apoptosis (PUMA, also known as BBC3) pathway (Portela et al 2015), although it has not yet been shown whether FGF18 alters p53 signaling. Most intriguingly, FGF18 does not result in the typical phosphorylation of MAPK3/1, but does phosphorylate MAPK14 (also known as p38); increased activity of MAPK14 has been linked to apoptosis in ovarian cells (Uma et al 2003, Bu et al 2006.…”

Section: The Role Of the Fgf8 Family In Follicle Developmentmentioning

confidence: 99%

“…Horizontal lines indicate no effect; NA, data not available. Data from Miyoshi et al (2010), Jiang et al (2011Jiang et al ( , 2013 and Portela et al (2015). intracellular signaling and/or ii) interactions between FGFs, FGFRs, and HSPGs.…”

Section: The Basis For Divergent Signaling Of Related Fgfsmentioning

confidence: 99%

“…This has been correlated with sustained phosphorylation of MAPK3/1 by FGF7 but transient (or weak) phosphorylation by FGF10 (Koyama et al 2008, Francavilla et al 2013, owing to a difference in the pattern of tyrosine phosphorylation in the kinase domain of FGFR2b (Francavilla et al 2013 (Crossley & Martin 1995). These splicing events result in a short form (FGF8a) and a longer form (FGF8b) among others, and it is recombinant FGF8b that has been used in studies of the ovary (Sugiura et al 2007, Portela et al 2015. FGF8a and FGF8b differ in their biological activities, as FGF8a induces expansion of the embryonic midbrain (in a manner similar to FGF18), whereas it is FGF8b that transforms the embryonic midbrain into a cerebellum (Liu et al 2003, Sato & Nakamura 2004.…”

Section: Differential Intracellular Signalingmentioning

confidence: 99%

See 2 more Smart Citations

Mechanisms of fibroblast growth factor signaling in the ovarian follicle

Price

2015

Journal of Endocrinology

View full text Add to dashboard Cite

Fibroblast growth factors (FGFs) have been shown to alter growth and differentiation of reproductive tissues in a variety of species. Within the female reproductive tract, the effects of FGFs have been focused on the ovary, and the most studied one is FGF2, which stimulates granulosa cell proliferation and decreases differentiation (decreased steroidogenesis). Other FGFs have also been implicated in ovarian function, and this review summarizes the effects of members of two subfamilies on ovarian function; the FGF7 subfamily that also contains FGF10, and the FGF8 subfamily that also contains FGF18. There are data to suggest that FGF8 and FGF18 have distinct actions on granulosa cells, despite their apparent similar receptor binding properties. Studies of non-reproductive developmental biology also indicate that FGF8 is distinct from FGF18, and that FGF7 is also distinct from FGF10 despite similar receptor binding properties. In this review, the potential mechanisms of differential action of FGF7/FGF10 and FGF8/FGF18 during organogenesis will be reviewed and placed in the context of follicle development. A model is proposed in which FGF8 and FGF18 differentially activate receptors depending on the properties of the extracellular matrix in the follicle.

show abstract

Endothelial cell‐derived fibroblast growth factor‐18 regulates ovarian function in sheep

Estienne

Relav

Benkoura

et al. 2022

Journal Cellular Physiology

View full text Add to dashboard Cite

Increasing the efficiency of farm animal reproduction is necessary to reduce the environmental impact of food production systems. One approach is to increase the number of healthy eggs (oocytes) produced per female for fertilization, thus it is important to understand factors that decrease oocyte health. One paracrine factor that decreases ovarian follicle growth is fibroblast growth factor 18 (FGF18) secreted by cells in the theca layer of the ovarian follicle, however the factors that regulate FGF18 secretion are unknown. In this study we hypothesized that FGF18 secretion is controled by intrafollicular factors and is linked to fertility, which we tested by using cell culture and sheep genetic models in vivo. Separation of theca cell populations revealed that FGF18 messenger RNA (mRNA) is located mainly in thecal endothelial rather than endocrine cells, and immunohistochemistry localized FGF18 protein to microvessels in the theca layer in situ. Culture of ovine theca‐derived endothelial cells was used to demonstrate stimulation of FGF18 mRNA and protein abundance by bone morphogenetic protein 4 (BMP4), a growth factor derived from theca endocrine cells. Taking advantage of a sheep genetic model, we demonstrate reduced ovarian and peripheral FGF18 concentrations in the hyperprolific Booroola ewe harboring the FecBB mutation in BMPR1B. These data suggest a novel control of fertility by follicular endothelial cells, in which theca endocrine cells secrete BMP4 that stimulates the secretion of FGF18 from thecal endothelial cells, which in turn diffuses into the granulosa cell layer and promotes apoptosis.

show abstract

The Role of Fibroblast Growth Factor-18 in Follicular Atresia in Cattle1

Cited by 33 publications

References 52 publications

Effects of the mycotoxin deoxynivalenol on steroidogenesis and apoptosis in granulosa cells

Effects of the mycotoxin deoxynivalenol on steroidogenesis and apoptosis in granulosa cells

Mechanisms of fibroblast growth factor signaling in the ovarian follicle

Endothelial cell‐derived fibroblast growth factor‐18 regulates ovarian function in sheep

Contact Info

Product

Resources

About