scholarly journals Brain-derived neurotrophic factor promotes bovine oocyte cytoplasmic competence for embryo development

Reproduction ◽  
2005 ◽  
Vol 129 (4) ◽  
pp. 423-434 ◽  
Author(s):  
S J Martins da Silva ◽  
J O Gardner ◽  
J E Taylor ◽  
A Springbett ◽  
P A De Sousa ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Embryo Development ◽  
Neurotrophic Factor ◽  
Calf Serum ◽  
Brain Derived Neurotrophic Factor ◽  
Positive Control ◽  
Neurotrophin Receptor ◽  
Bovine Oocyte ◽  
Cytoplasmic Competence

The ability of an oocyte to support early embryonic development requires both nuclear and cytoplasmic maturation. We have investigated the effects of brain-derived neurotrophic factor (BDNF) on maturation of the bovine oocyte and embryo development after parthenogenetic activation. By RT-PCR and immunohistochemistry, cumulus and oocytes were shown to express mRNA and protein for BDNF and the p75 common neurotrophin receptor. However, mRNA for the BDNF-specific full length and truncated isoforms of the TrkB receptor are only detected in cumulus, suggesting that oocytes and cumulus differ in their capacity to respond to neurotrophin signalling. Inin vitromaturation experiments, the proportion of cumulus oocyte complexes maturing to metaphase II was not altered by BDNF in groups lacking fetal calf serum (FCS), but was significantly lower than the positive control containing 10% FCS (P< 0.01). However, after maturation, the proportion of parthenogenetically activated oocytes forming blastocysts was highest for 10 ng/ml BDNF (24%,n= 95) followed by 100 ng/ml BDNF (18%,n= 91) and 10% FCS (15%,n= 103), which in turn were greater than no serum (10%,n= 83;P< 0.01). Maturation in the presence of a BDNF blocking antibody resulted in a blastocyst yield that was comparable to the absence of serum, and lower than in the presence of BDNF (P< 0.01). Similar effects on progression to metaphase II and blastocyst formation were observed using oocytes matured without cumulus. Together, these results provide the first evidence for a role for neurotrophins in promoting oocyte cytoplasmic competence to support embryonic development, despite being insufficient in the absence of serum to enhance nuclear maturation.

The effects of brain-derived neurotrophic factor and metformin on in vitro developmental competence of bovine oocytes

Zygote ◽  
2009 ◽  
Vol 17 (3) ◽  
pp. 187-193 ◽  
Author(s):  
So Gun Hong ◽  
Goo Jang ◽  
Hyun Ju Oh ◽  
Ok Jae Koo ◽  
Jung Eun Park ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Embryo Development ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Early Embryo ◽  
Developmental Competence ◽  
Blastocyst Development ◽  
Cell Stage ◽  
Significant Difference

SummaryBrain-derived neurotrophic factor (BDNF) signalling via tyrosine kinase B receptors may play an important role in ovarian development and function. It has been reported that metformin elevates the activity of Tyrosine kinase receptors and may amplify BDNF signalling. The objective of this study was to investigate the effect of BDNF during in vitro maturation (IVM) and/or in vitro culture (IVC) (Experiment 1), and to evaluate the collaborative effect of BDNF and metformin treatment on the developmental competence of bovine in vitro fertilized (IVF) embryos (Experiment 2). In Experiment 1, BDNF, which was added to our previously established IVM systems, significantly increased the proportions of MII oocytes at both 10 ng/ml (86.7%) and 100 ng/ml (85.4%) compared with the control (64.0%). However, there was no statistically significant difference in blastocyst development between the control or BDNF-supplemented groups. In Experiment 2, in order to investigate the effect of BDNF (10 ng/ml) and/or metformin (10−5 M) per se, TCM-199 without serum and hormones was used as the control IVM medium. The BDNF (48.3%) and BDNF plus metformin (56.5%) significantly enhanced the proportions of MII oocytes compared with the control (34.4%). Although, BDNF or metformin alone had no effect in embryo development, BDNF plus metformin significantly improved early embryo development to the 8–16-cell stage compared with the control (16.5 vs. 5.5%). In conclusion, the combination of BDNF and metformin may have a collaborative effect during the IVM period. These results could further contribute to the establishment of a more efficient bovine in vitro embryo production system.

309 ADDITION OF BRAIN-DERIVED NEUROTROPHIC FACTOR IN MATURATION MEDIUM IMPROVED IN VITRO MEIOTIC COMPETENCE OF OVINE OOCYTES AND SUBSEQUENT PARTHENOGENETIC DEVELOPMENT

2015 ◽  
Vol 27 (1) ◽  
pp. 243
Author(s):  
A. H. Abazari-kia ◽  
A. Mohammadi-Sangcheshmeh ◽  
M. Salehi ◽  
M. Zhandi
Keyword(s):  
Embryonic Development ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Culture Conditions ◽  
Control Group ◽  
P Value ◽  
Oocyte Competence ◽  
Maturation Medium ◽  
And Control

Overall efficiency of in vitro embryo production has remained low despite extensive effort to understand the effects of culture conditions, media composition, and supplementation. Brain-derived neurotrophic factor (BDNF), which is a physiologically important neurotrophin, has been used to enhance oocyte maturation in some previous studies (Lee et al. 2007; Zhang et al. 2010). However, the efficacy of BDNF to improve oocyte competence has not been fully established especially in ovine. Therefore, the present study aimed to evaluate the effect of BDNF during in vitro maturation (IVM) on maturation rate, intracellular glutathione (GSH) content, and embryonic development in sheep oocytes. Cumulus-oocyte complexes (COC) were obtained from ovaries of ewes. The COC were placed in maturation medium supplemented with either 10 (IVM-B10) or 100 (IVM-B100) ng mL–1 of BDNF (PeproTech, London, UK). Oocytes in control group were incubated in the same maturation medium without BDNF. The IVM was performed in a humidified atmosphere containing 5% CO2, 5% O2, and 90% N2 at 38.5°C for 24 h. After IVM, several oocytes from the IVM-B10 (n = 110), IVM-B100 (n = 124), and control (n = 110) groups were stained with Hoechst and were evaluated in relation to their metaphase-II rate. To measure GSH content, several oocytes from the IVM-B10 (n = 28), IVM-B100 (n = 33), and control (n = 37) groups were incubated in tyrodes medium containing 10 µM Cell Tracker blue for 30 min and transferred under fluorescence microscope, with digital images analysed by image J software. To evaluate the embryonic development, several oocytes from IVM-B10 (n = 145), IVM-B100 (n = 137), and control (n = 143) groups were subjected to parthenogenetic activation by applying 1 min of exposure to 2.5 µM ionomycin followed by 2 mM 6-DMAP treatment for 3 h. After stimulation, oocytes were cultured in CR1aa medium for 7 days under the conditions stated previously. Four replications were performed. The metaphase-II rate, cleavage, and blastocyst rates were compared by x2 analysis. The GSH content was analysed by one-way ANOVA. A P-value of less than 0.05 was considered significant. The results showed that metaphase-II rate was higher in the IVM-B100 group (88.7%), as compared with the control group (77.3%), but not significant as compared with that in the IVM-B10 group (84.5%). No difference was also found between the IVM-B10 group and control group in terms of the metaphase-II rate. Oocytes in the IVM-B10 group revealed a higher (96.8%) GSH content than both of the IVM-B100 (86.9%) and control (86.3%) groups. There was, however, no difference in the GSH content between the IVM-B100 group and control group. The proportion of cleaved embryos was not different between the groups; however, the blastocyst rate was higher in both the IVM-B10 (37.9%) and IVM-B100 (39.3%) groups compared with the control group (22.4%). Collectively, the results of this study showed that supplementation of IVM media with BDNF promoted nuclear maturation, increased GSH content, and stimulated in vitro embryonic development in ovine.

281 INFLUENCE OF DEFINED AND COMPLEX CULTURE MEDIA ON FERTILIZATION AND EMBRYONIC DEVELOPMENT OF IN VITRO-MATURED CAPRINE OOCYTES

2010 ◽  
Vol 22 (1) ◽  
pp. 297 ◽  
Author(s):  
S. D. Kharche ◽  
P. Yadav ◽  
A. K. Goel ◽  
S. K. Jindal ◽  
M. C. Sharma
Keyword(s):  
Embryonic Development ◽  
Embryo Development ◽  
Culture Media ◽  
Calf Serum ◽  
Defined Medium ◽  
Cleavage Rate ◽  
Group 3 ◽  
Group 2 ◽  
Complex Culture

Complex media containing serum and/or co-culture with somatic cells result in satisfactory development, although the undefined conditions make it impossible to examine requirements of the embryos. Our objective was to compare defined and complex culture systems for their ability to support normal caprine embryonic development. In total, 3844 selected cumulus oocyte complexes (COC) were used for maturation in TCM-199 containing 10% newborn calf serum (NCS), 3 mg mL-1 BSA, 5 μg mL-1 FSH, 5 μg mL-1 LH, and 1 μg mL-1 estradiol-17β and 10 ng mL-1 epidermal growth factor. After 27 h of maturation, oocytes were separated from cumulus and corona cells by treatment with 0.1% hyaluronidase and by passing through a fine-bore pipette. They were then washed in sperm TALP and fertilized in a drop of fertilization TALP (20% estrous goat serum and 10 μg mL-1 heparin) containing 1 to 2 × 106 spermatozoa per mL. Oocytes-sperm after 18 h of co-incubation were washed in embryo development medium 15 to 20 times and randomly divided into 3 groups. Fertilized oocytes were cultured for 10 days in TCM-199 containing 10% NCS and 4 mg mL-1 BSA (group 1; n = 1511), synthetic oviductal fluid (SOF) containing 10% NCS and 4 mg mL-1 BSA (group 2; n = 1333) or potassium simplex optimization medium (KSOM) containing 10% NCS and 4 mg mL-1 BSA (group 3; n = 1000). The cleavage rate for groups 1, 2, and 3 were 13.6, 11.7, and 31.4%, respectively. All data were analyzed by one-way ANOVA; developmental data were arc sin transformed. The cleavage rate was significantly higher (P < 0.01) for group 3 than for groups 1 and 2. Similarly, embryo development up to morula stage was higher (P < 0.05) in KSOM compared with TCM-199 and SOF. This study shows that good development of embryos can be obtained in a completely defined medium and was better in KSOM than in SOF.

scholarly journals TrkB deubiquitylation by USP8 regulates receptor levels and BDNF-dependent neuronal differentiation

2020 ◽  
Vol 133 (24) ◽  
pp. jcs247841 ◽  
Author(s):  
Carlos Martín-Rodríguez ◽  
Minseok Song ◽  
Begoña Anta ◽  
Francisco J. González-Calvo ◽  
Rubén Deogracias ◽  
...  
Keyword(s):  
Neuronal Differentiation ◽  
Neurotrophic Factor ◽  
Tyrosine Kinases ◽  
Hippocampal Neurons ◽  
Receptor Tyrosine Kinases ◽  
Neurotrophin Receptor ◽  
C Terminus ◽  
Carboxyl Terminal

ABSTRACTUbiquitylation of receptor tyrosine kinases (RTKs) regulates both the levels and functions of these receptors. The neurotrophin receptor TrkB (also known as NTRK2), a RTK, is ubiquitylated upon activation by brain-derived neurotrophic factor (BDNF) binding. Although TrkB ubiquitylation has been demonstrated, there is a lack of knowledge regarding the precise repertoire of proteins that regulates TrkB ubiquitylation. Here, we provide mechanistic evidence indicating that ubiquitin carboxyl-terminal hydrolase 8 (USP8) modulates BDNF- and TrkB-dependent neuronal differentiation. USP8 binds to the C-terminus of TrkB using its microtubule-interacting domain (MIT). Immunopurified USP8 deubiquitylates TrkB in vitro, whereas knockdown of USP8 results in enhanced ubiquitylation of TrkB upon BDNF treatment in neurons. As a consequence of USP8 depletion, TrkB levels and its activation are reduced. Moreover, USP8 protein regulates the differentiation and correct BDNF-dependent dendritic formation of hippocampal neurons in vitro and in vivo. We conclude that USP8 positively regulates the levels and activation of TrkB, modulating BDNF-dependent neuronal differentiation.This article has an associated First Person interview with the first author of the paper.

scholarly journals Interferon beta-1a induces expression of brain-derived neurotrophic factor in human T lymphocytes in vitro and not in vivo

2020 ◽  
Vol 15 (1) ◽  
pp. FNL38 ◽  
Author(s):  
Zarlascht Karmand ◽  
Hans-Peter Hartung ◽  
Oliver Neuhaus
Keyword(s):  
T Cell ◽  
Neurotrophic Factor ◽  
Serum Levels ◽  
Brain Derived Neurotrophic Factor ◽  
Peripheral Blood Lymphocytes ◽  
T Cell Proliferation ◽  
Bdnf Expression ◽  
Healthy Donors

Aim: To detect IFN β-1a-induced expression of brain-derived neurotrophic factor (BDNF) to undermine the hypothesis of IFN β-1a-associated neuroprotection in multiple sclerosis (MS). Methods: The influence of IFN β-1a on in vitro activated peripheral blood lymphocytes from healthy donors was tested. Proliferation analyses were made to detect T-cell growth. BDNF expression was measured by standard ELISA. To assess the influence of IFN β-1a on BDNF expression in vivo, BDNF serum levels of MS patients treated with IFN β-1a were compared with those of untreated patients. Results: IFN β-1a inhibited T-cell proliferation dose dependently. It induced BDNF expression at middle concentrations. MS patients treated with IFN β-1a exhibited significantly lower BDNF serum levels than untreated patients. Conclusion: IFN β-1a may promote neuroprotection by inducing BDNF expression, but its importance in vivo remains open.

scholarly journals Regulation of preimplantation embryo development by brain-derived neurotrophic factor

2007 ◽  
Vol 311 (1) ◽  
pp. 147-158 ◽  
Author(s):  
Kazuhiro Kawamura ◽  
Nanami Kawamura ◽  
Jun Fukuda ◽  
Jin Kumagai ◽  
Aaron J.W. Hsueh ◽  
...  
Keyword(s):  
Embryo Development ◽  
Neurotrophic Factor ◽  
Preimplantation Embryo ◽  
Brain Derived Neurotrophic Factor ◽  
Preimplantation Embryo Development

scholarly journals Localized delivery of fibroblast growth factor–2 and brain-derived neurotrophic factor reduces spontaneous seizures in an epilepsy model

2009 ◽  
Vol 106 (17) ◽  
pp. 7191-7196 ◽  
Author(s):  
Beatrice Paradiso ◽  
Peggy Marconi ◽  
Silvia Zucchini ◽  
Elena Berto ◽  
Anna Binaschi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Neurotrophic Factor ◽  
Viral Vectors ◽  
Neuronal Damage ◽  
Brain Derived Neurotrophic Factor ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Damage Limitation

A loss of neurons is observed in the hippocampus of many patients with epilepsies of temporal lobe origin. It has been hypothesized that damage limitation or repair, for example using neurotrophic factors (NTFs), may prevent the transformation of a normal tissue into epileptic (epileptogenesis). Here, we used viral vectors to locally supplement two NTFs, fibroblast growth factor–2 (FGF-2) and brain-derived neurotrophic factor (BDNF), when epileptogenic damage was already in place. These vectors were first characterized in vitro, where they increased proliferation of neural progenitors and favored their differentiation into neurons, and they were then tested in a model of status epilepticus-induced neurodegeneration and epileptogenesis. When injected in a lesioned hippocampus, FGF-2/BDNF expressing vectors increased neuronogenesis, embanked neuronal damage, and reduced epileptogenesis. It is concluded that reduction of damage reduces epileptogenesis and that supplementing specific NTFs in lesion areas represents a new approach to the therapy of neuronal damage and of its consequences.

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