Zinc supplementation promotes oocyte maturation and subsequent embryonic development in sheep.

Zinc plays a crucial role in the growth and reproductive functions of animals. Despite the positive effects of zinc that have been reported in oocytes of cows, pigs, yaks, and other animals, the influence of zinc on sheep is little known. To investigate the effect of zinc on the in vitro maturation of sheep oocytes and subsequent parthenogenesis-activated embryonic development, we added different concentrations of zinc sulfate to the in vitro maturation (IVM) culture medium. The IVM culture medium with zinc improved the maturation of sheep oocytes and the subsequent blastocyst rate after parthenogenesis activation. Notably, it also enhanced the level of glutathione and mitochondrial activity while reducing levels of reactive oxygen species. Thus, zinc addition to the IVM medium improved the quality of oocytes with a positive effect on the subsequent development of oocytes and embryos.

Coenzyme Q10 Supplement Rescues Postovulatory Oocyte Aging by Regulating SIRT4 Expression.

BACKGROUND: High-quality of the oocyte is crucial for embryo development and the success of human-assisted reproduction. The postovulatory aged oocytes lose developmental competence with mitochondrial dysfunction and oxidative stress. Coenzyme Q10 (CoQ10) is widely distributed in the membranes of cells and has an important role in the mitochondrial respiration chain against oxidative stress and modulation of gene expression. OBJECTIVE: The objective of this study is to investigate the functions and mechanisms of CoQ10 on delaying postovulatory oocyte aging. METHODS: Quantitative real-time PCR and Immunofluorescence staining were used to determine the expression patterns of the biogenesis genes of CoQ10 in postovulatory aged oocytes compared with fresh oocytes. The mitochondrial function, apoptosis, reactive oxygen species (ROS) accumulation and spindle abnormalities were investigated after treatment with 10 µM CoQ10 in aged groups. SIRT4 siRNA or capped RNA was injected into oocytes to investigate the function of SIRT4 on postovulatory oocyte aging and the relationship between CoQ10 and SIRT4. RESULTS: Multiple CoQ10 biosynthesis enzymes are insufficient, and a supplement of CoQ10 can improve oocyte quality and elevate the development competency of postovulatory aged oocytes. CoQ10 can attenuate the aging-induced abnormalities, including mitochondrial dysfunction, ROS accumulation, spindle abnormalities, and apoptosis in postovulatory aged oocytes. Furthermore, SIRT4, which was first found to be up-regulated in postovulatory aged oocytes, decreased following CoQ10 treatment. Finally, knockdown of SIRT4 can rescue aging-induced dysfunction of mitochondria, and the efficiency of CoQ10 rescuing dysfunction of mitochondria can be weakened by SIRT4 overexpression. CONCLUSION: Supplement of CoQ10 protects oocytes from postovulatory aging by inhibiting SIRT4 increase.

Retinal inputs signal astrocytes to recruit interneurons into visual thalamus.

Inhibitory interneurons comprise a fraction of the total neurons in the visual thalamus but are essential for sharpening receptive field properties and improving contrast-gain of retinogeniculate transmission. During early development, these interneurons undergo long-range migration from germinal zones, a process regulated by the innervation of the visual thalamus by retinal ganglion cells. Here, using transcriptomic approaches, we identified a motogenic cue, fibroblast growth factor 15 (FGF15), whose expression in the visual thalamus is regulated by retinal input. Targeted deletion of functional FGF15 in mice led to a reduction in thalamic GABAergic interneurons similar to that observed in the absence of retinal input. This loss may be attributed, at least in part, to misrouting of interneurons into nonvisual thalamic nuclei. Unexpectedly, expression analysis revealed that FGF15 is generated by thalamic astrocytes and not retino-recipient neurons. Thus, these data show that retinal inputs signal through astrocytes to direct the long-range recruitment of interneurons into the visual thalamus.

Melatonin supplementation during in vitro maturation of oocyte enhances subsequent development of bovine cloned embryos.

Oocyte quality, which is directly related to reprogramming competence, is a major important limiting factor in animal cloning efficiency. Compared with oocytes matured in vivo, in vitro matured oocytes exhibit lower oocyte quality and reprogramming competence primarily because of their higher levels of reactive oxygen species. In this study, we investigate whether supplementing the oocyte maturation medium with melatonin, a free radical scavenger, could improve oocyte quality and reprogramming competence. We found that 10-9 M melatonin effectively alleviated oxidative stress, markedly decreased early apoptosis levels, recovered the integrity of mitochondria, ameliorated the spindle assembly and chromosome alignment in oocytes, and significantly promoted subsequent cloned embryo development in vitro. We also analyzed the effects of melatonin on epigenetic modifications in bovine oocytes. Melatonin increased the global H3K9 acetylation levels, reduced the H3K9 methylation levels, and minimally affected DNA methylation and hydroxymethylation. Genome-wide expression analysis of genes in melatonin-treated and nontreated oocytes was also conducted by high-throughput RNA sequencing. Our results indicated that melatonin ameliorates oocyte oxidative stress and improves subsequent in vitro development of bovine cloned embryos.

Distribution and development of molecularly distinct perineuronal nets in visual thalamus.

Visual information is detected by the retina and transmitted into the brain by retinal ganglion cells. In rodents, the visual thalamus is a major recipient of retinal ganglion cells axons and is divided into three functionally distinct nuclei: the dorsal lateral geniculate nucleus (dLGN), ventral LGN (vLGN), and intergeniculate leaflet. Despite being densely innervated by retinal input, each nucleus in rodent visual thalamus possesses diverse molecular profiles which underpin their unique circuitry and cytoarchitecture. Here, we combined large-scale unbiased proteomic and transcriptomic analyses to elucidate the molecular expression profiles of the developing mouse dLGN and vLGN. We identified several extracellular matrix proteins as differentially expressed in these regions, particularly constituent molecules of perineuronal nets (PNNs). Remarkably, we discovered at least two types of molecularly distinct Aggrecan-rich PNN populations in vLGN, exhibiting non-overlapping spatial, temporal, and cell-type specific expression patterns. The mechanisms responsible for the formation of these two populations of PNNs also differ as the formation of Cat315+ PNNs (but not WFA+ PNNs) required input from the retina. This study is first to suggest that cell type- and molecularly specific supramolecular assemblies of extracellular matrix may play important roles in the circuitry associated with the subcortical visual system and in the processing of visual information. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/. Cover Image for this issue: doi: 10.1111/jnc.14203.

LRRTM1 underlies synaptic convergence in visual thalamus.

It has long been thought that the mammalian visual system is organized into parallel pathways, with incoming visual signals being parsed in the retina based on feature (e.g. color, contrast and motion) and then transmitted to the brain in unmixed, feature-specific channels. To faithfully convey feature-specific information from retina to cortex, thalamic relay cells must receive inputs from only a small number of functionally similar retinal ganglion cells. However, recent studies challenged this by revealing substantial levels of retinal convergence onto relay cells. Here, we sought to identify mechanisms responsible for the assembly of such convergence. Using an unbiased transcriptomics approach and targeted mutant mice, we discovered a critical role for the synaptic adhesion molecule Leucine Rich Repeat Transmembrane Neuronal 1 (LRRTM1) in the emergence of retinothalamic convergence. Importantly, LRRTM1 mutant mice display impairment in visual behaviors, suggesting a functional role of retinothalamic convergence in vision.

Multiple Retinal Axons Converge onto Relay Cells in the Adult Mouse Thalamus.

Activity-dependent refinement of neural circuits is a fundamental principle of neural development. This process has been well studied at retinogeniculate synapses-synapses that form between retinal ganglion cells (RGCs) and relay cells within the dorsal lateral geniculate nucleus. Physiological studies suggest that shortly after birth, inputs from ∼20 RGCs converge onto relay cells. Subsequently, all but just one to two of these inputs are eliminated. Despite widespread acceptance, this notion is at odds with ultrastructural studies showing numerous retinal terminals clustering onto relay cell dendrites in the adult. Here, we explored this discrepancy using brainbow AAVs and serial block face scanning electron microscopy (SBFSEM). Results with both approaches demonstrate that terminals from numerous RGCs cluster onto relay cell dendrites, challenging the notion that only one to two RGCs innervate each relay cell. These findings force us to re-evaluate our understanding of subcortical visual circuitry.

Valproic acid improves the in vitro development competence of bovine somatic cell nuclear transfer embryos.

The present study was carried out to examine the effect of valproic acid (VPA), an important histone deacetylase inhibitor, on the in vitro development and expression of the epigenetic marker histone H3 lysine 9 (H3K9ac) in bovine somatic cell nuclear transfer (SCNT) embryos. We found that treatment with 4 mM VPA for 24 h could significantly improve the development of bovine SCNT embryos. Compared with the no-treatment group, the cleavage rate was higher (69.79 ± 0.99% vs. 65.11 ± 1.02%, p<0.05), as was the blastocyst rate (39.99 ± 1.29% vs. 34.87 ± 1.74%, p<0.05). Moreover, the rate of apoptosis (1.91 ± 0.48% vs. 5.67 ± 0.40%, p<0.05) in blastocysts was greatly reduced after VPA treatment. Valproic acid treatment also increased the immunofluorescent signal for H3K9ac in SCNT embryos in a pattern similar to that of in vitro fertilized (IVF) embryos. In conclusion, we demonstrated that VPA can significantly improve the in vitro developmental competence and enhance the nuclear reprogramming of bovine SCNT embryos.

[Relationship between tardive dyskinesia and the polymorphism of superoxide dismutase val9Ala and efficacy of Chaihu Taoren Capsules on it].

OBJECTIVE: To investigate the relationship between efficacy of Chaihu Taoren Decoction (CTD) and the polymorphism of valine-alanine missense mutation of 9th codan (Val9Ala, T1183C) of superoxide dismutase (SOD) in patients with tardive dyskinesia (TD). METHODS: Severity of TD was assessed by abnormal involuntary movement scale (AIMS), and the psychologic symptoms were rated by the positive and negative symptoms scale (PANSS). The sample size consisted of 119 patients with TD assigned to the TD group, 129 patients of chronic schizophrenia with the general condition matched strictly with that of the enrolled TD patients assigned to the non-TD group, and 148 healthy persons assigned to the normal group. The gene distribution rate of Val9Ala gene was analyzed using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) analysis, and the therapeutic effect of CTD on 36 patients with TD was observed after 12 weeks treatment. RESULTS: There was no significant difference in genotype and allelic gene frequency of SOD Val9Ala among the TD, non-TD and normal groups (P > 0.05). Comparison of the AIMS score in TD patients with various Val9Ala genotypes showed that the difference of AIMS scores in patients with TT and CT genotype was not significant (P > 0.05), but CTD did show a better efficacy in TD patients with CT heterozygote than in those with TT homozygote (P < 0.05). CONCLUSION: The CTD could effectively relieve the symptoms of TD, its efficacy might be related with the genotype of SOD, and 9Ala is considered to be a protective factor for the susceptibility to TD.