Decorin is a part of the ovarian extracellular matrix in primates and may act as a signaling molecule

Adam, Marion; Saller, S.; Ströbl, Stephan; Hennebold, Jon D.; Dissen, Gregory A.; Ojeda, Sergio R.; Stouffer, Richard L.; Berg, Dieter; Berg, U.; Mayerhofer, Artur

doi:10.1093/humrep/des297

Cited by 21 publications

(14 citation statements)

References 47 publications

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“…Amplified PCR products were separated and visualized by ethidium bromide stained agarose gels. The identities of all PCR products were verified by sequencing [30, 35]. For primer sequence information, please see Table 3.…”

Section: Methodsmentioning

confidence: 99%

“…The activities of the effector caspases 3/7 were determined following exposure of human GCs to proNGF and NGF [34, 35]. Cells were cultured for 2 days, seeded on white walled 96-well plates (20000 cells per well) and then treated with different concentrations of proNGF and NGF for 24 h. Staurosporine (1 μM; Sigma-Aldrich) was used as positive control.…”

Section: Methodsmentioning

confidence: 99%

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Pro-nerve growth factor in the ovary and human granulosa cells

Meinel

Blohberger

Berg

et al. 2015

Hormone Molecular Biology and Clinical Investigation

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Background Pro-nerve growth factor must be cleaved to generate mature NGF, which was suggested to be a factor involved in ovarian physiology and pathology. Extracellular proNGF can induce cell death in many tissues. Whether extracellular proNGF exists in the ovary and may play a role in the death of follicular cells or atresia was unknown. Material and Methods Immunohistochemistry of human and Rhesus monkey ovarian sections was performed. IVF-derived follicular fluid and human granulosa cells were studied by RT-PCR, qPCR, Western blotting, ATP- and caspase-assays. Results and Conclusions Immunohistochemistry of ovarian sections identified proNGF in granulosa cells and Western blotting of human isolated granulosa cells confirmed the presence of proNGF. Ovarian granulosa cells thus produce proNGF. Recombinant human proNGF even at high concentrations did not affect the levels of ATP or the activity of caspase 3/7, indicating that in granulosa cells proNGF does not induce death. In contrast, mature NGF, which was detected previously in follicular fluid, may be a trophic molecule for granulosa cells with unexpected functions. We found that in contrast to proNGF, NGF increased the levels of the transcription factor early growth response 1 and of the enzyme choline acetyl-transferase. A mechanism for the generation of mature NGF from proNGF in the follicular fluid may be extracellular enzymatic cleavage. The enzyme MMP7 is known to cleave proNGF and was identified in follicular fluid and as a product of granulosa cells. Thus the generation of NGF in the ovarian follicle may depend on MMP7.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Pro-nerve growth factor in the ovary and human granulosa cells

Meinel

Blohberger

Berg

et al. 2015

Hormone Molecular Biology and Clinical Investigation

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“…Using immunohistochemistry in adult rhesus monkey and human ovaries, it was found that DCN is expressed in theca cells, the corpus luteum (CL), and follicular fluid (FF) [13] Moreover, it was shown that adding DCN to cultured CGs, elevated intracellular Ca2+ levels and phosphorylation of EGFR. Based on these results the study suggested that DCN plays multiple roles in granulosa cells, including folliculogenesis, ovulation, and survival of the CL [14]. More recent work demonstrated that DCN regulates apoptosis and cell cycle of granulosa cells in goat ovaries [15].…”

Section: Introductionmentioning

confidence: 87%

Elucidating Decorin’s role in the preovulatory follicle

et al. 2020

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Background: DCN (decorin) is a proteoglycan known to be involved in regulating cell proliferation, collagen fibril organization and migration. In our global transcriptome RNA-sequencing approach to systematically identify new ovulation-associated genes, DCN was identified as one of the highly regulated genes. We therefore hypothesize that DCN may have a role in ovulatory processes such as cell migration and proliferation. Aim: To characterize the expression, regulation and function of the proteoglycan DCN in the human ovarian follicles during the preovulatory period. Methods: The in-vivo expression of DCN mRNA in mural (MGCs) and cumulus (CGCs) granulosa cells was characterized using quantitative RT-PCR and western blot. A signaling study was performed by treating human MGCs cultures with gonadotropins and different stimulators and inhibitors to determine their effect on DCN expression by qRT-PCR and elucidate the pathways regulating these proteins. In a functional study, KGN granulosa cell line was used to study cell migration with a scratch assay. Results: DCN mRNA expression was significantly higher in MGCs compared to CGCs. DCN mRNA was significantly higher in CGCs surrounding mature metaphase II (MII) oocytes compared to CGCs of germinal vesicle (GV) and metaphase I (MI) oocytes. hCG significantly increased DCN mRNA and protein expression levels in cultured MGCs. Using signal transduction activators and inhibitors, we demonstrated that DCN induction by LH/hCG is carried out via PKA, PKC, ERK/MEK, and PI3K pathways. We showed that DCN expression is also induced in high-density cell cultures, in a dose-dependent pattern. In addition, progesterone induced a significant increase in DCN secretion to the media. MGCs from follicles of endometriosis patients exhibited reduced (about 20% of) mRNA transcriptions levels compared to MGCs follicles of control patients. More significantly, we found that DCN has an inhibiting effect on KGN cell migration. Conclusions:Our study indicates that DCN is a unique ovulatory gene. Our findings support the hypothesis that DCN plays an important new role during the preovulatory period and ovulation, and stress its involvement in endometriosis infertility. A better understanding of DCN role in ovulation and endometriosis may provide treatment for some types of infertility.

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“…Specific ECM molecules, including the multi-adhesive basement membrane protein fibronectin (FN) and a small leucine-rich proteoglycan decorin (DCN), are required for folliculogenesis and ovulation (Adam et al, 2012;Yasuda et al, 2005). In a previous study, we have demonstrated that DCN, a differentially expressed gene, was screened from ovarian tissues between polytocous and monotocous dairy goats by suppressive subtractive hybridization (Zhu et al, unpublished data).…”

mentioning

confidence: 99%

“…The binding causes phosphorylation and activation of EGFR and can be followed by downregulation of EGFR signaling, resulting in a long-term blockage of EGF/EGFR actions (Adam et al, 2011;Csordas et al, 2000). Adam et al (2012) furthermore indicated that the EGFR is one of the growth factor receptors directly targeted by DCN in human GCs and DCN is a local regulator of folliculogenesis, ovulation and the functional lifespan of the CL in primates. Recent studies demonstrated that the expression of FN was elevated in the superstimulation group and its expression was reported to be inversely related to follicle maturation (Berkholtz et al, 2006;Dias et al, 2013;Yasuda et al, 2005).…”

mentioning

confidence: 99%