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BACKGROUND Traditional studies focused on DNA as the heritable information carrier that passes the phenotype from parents to offspring. However, increasing evidence suggests that information, that is independent of the DNA sequence, termed epigenetic information, can be inherited between generations. Recently, in our lab, we found that prediabetes in fathers increases the susceptibility to diabetes in offspring through gametic cytosine methylation changes. Paternal prediabetes changed overall methylation patterns in sperm, and a large portion of differentially methylated loci can be transmitted to pancreatic islets of offspring up to the second generation. In this review, we survey the extensive examples of environmentally induced epigenetic inheritance in various species, ranging from Caenorhabditis elegans to humans. We focus mainly on elucidating the molecular basis of environmental epigenetic inheritance through gametes, which is an emerging theme and has important implications for explaining the prevalence of obesity, type 2 diabetes and other chronic non-genetic diseases, which is also important for understanding the influence of environmental exposures on reproductive and overall health in offspring. METHODS For this review, we included relevant data and information obtained through a PubMed database search for all English language articles published up to August 2014 which included the term ‘environmental epigenetic inheritance’ and ‘transgenerational epigenetic inheritance’. We focused on research papers using animal models including Drosophila, C. elegans, mouse and rat. Human data were also included. RESULTS Evidence from animal models suggests that environmental epigenetic inheritance through gametes exists in various species. Extensive molecular evidence suggests that epigenetic information carriers including DNA methylation, non-coding RNAs and chromatin proteins in gametes play important roles in the transmission of phenotypes from parents to offspring. CONCLUSIONS Given the large number of experimental evidence from various organisms, it is clear that parental environmental alterations can affect the phenotypes of offspring through gametic epigenetic alterations. This more recent thinking based on new data may have implications in explaining the prevalence of obesity, type 2 diabetes and other chronic non-genetic diseases. This also implies that, in the near future, epigenetic factors which are heritable should be regarded important in determining the risk of certain diseases. Moreover, identification of epigenetic markers in gametes (polar body or sperm) may hold great promise for predicting susceptibility to and preventing certain non-genetic diseases in offspring, as well as providing indications on parental environmental exposures. [ABSTRACT FROM PUBLISHER]

Errors in chromosome segregation or distribution may result in aneuploid embryo formation, which causes implantation failure, spontaneous abortion, genetic diseases, or embryo death. Embryonic aneuploidy occurs when chromosome aberrations are present in gametes or early embryos. To date, it is still unclear whether the spindle assembly checkpoint (SAC) is required for the regulation of mitotic cell cycle progression to ensure mitotic fidelity during preimplantation development. In this study, using overexpression and RNA interference (RNAi) approaches, we analyzed the role of SAC components (Bub3, BubR1 and Mad2) in mouse preimplantation embryos. Our data showed that overexpressed SAC components inhibited metaphase-anaphase transition by preventing sister chromatid segregation. Deletion of SAC components by RNAi accelerated the metaphase-anaphase transition during the first cleavage and caused micronuclei formation, chromosome misalignment and aneuploidy, which caused decreased implantation and delayed development. Furthermore, in the presence of the spindle-depolymerizing drug nocodazole, SAC depleted embryos failed to arrest at metaphase. Our results suggest that SAC is essential for the regulation of mitotic cell cycle progression in cleavage stage mouse embryos [ABSTRACT FROM AUTHOR]

Background: Moyamoya disease (MMD) is an uncommon cerebrovascular disease which leads to progressive stenosis and occlusion of the bilateral internal carotid artery and main intracerebral arteries. Concerns are always on how the hemisphere with infarction affects cognitive function, while little attention is paid to the role that the non-infarcted hemisphere plays. Therefore, we aimed to detect cortical indexes, especially cortical complexity in the left or right hemisphere separately in patients with MMD after stroke.Methods: 28 patients with MMD (14 males, 14 females) and 14 healthy controls were included in this study. All participants underwent cognitive tests and magnetic resonance imaging (MRI) scan. The preprocessing of three-dimensional T1 weighted images were performed by standard surface-based morphometry. Surface-based morphometry statistical analysis was carried out with a threshold of False Discovery Rate (FDR) P < 0.05 and fractal dimension (FD) was used to provide a quantitative description of cerebral cortical complexity.Results: Widespread cognitive dysfunctions were found in MMD patient with stroke. Extensive FD reduction in the left hemisphere with right-sided infarction, mainly in the superior temporal, inferior frontal, and insula, while the post central gyrus, superior parietal, and inferior parietal gyrus also showed a wide range of significant differences (FDR corrected P < 0.05). Meanwhile, FD changes in the right hemisphere with left-sided infarction are restricted to the precuneus and cingulate isthmus (FDR corrected P < 0.05).Conclusions: Extensive cognitive impairment was reconfirmed in Moyamoya disease with stroke, while wild and asymmetrical decrease of cortical complexity is observed on both sides. These differences could be relative to unbalanced cognitive dysfunction, and may be the result of a long-term chronic ischemia and compensatory of the contralateral hemisphere to the infarction. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic Moyamoya disease (MMD) impairs hemodynamic and cognitive function. The relationship between these changes, cerebral blood flow (CBF), and network connectivity remains largely unknown. The aim of this study was to increase understanding of the relationship between CBF, functional networks, and neurocognition in adults with asymptomatic MMD. We compared CBF and functional status in 26 patients with MMD and 20 healthy controls using arterial spin labeling and resting state functional magnetic resonance imaging sequences. At the same time, a detailed cognitive test was performed in 15 patients with no cerebral or lumen infarction who were selected by magnetic resonance imaging-T2 FLAIR screening.Results: Compared to the controls, the patients showed varying degrees of decline in their computational ability (simple subtraction, p = 0.009; complex subtraction, p = 0.006) and short-term memory (p = 0.042). The asymptomatic MMD group also showed decreased CBF in the left anterior central and left inferior frontal gyri of the island flap with multiple node abnormalities in the brain network and reduced network connectivity. There was a significant association of these changes with cognitive decline in the MMD group.Conclusions: In patients with asymptomatic MMD, disturbance of CBF and impaired brain network connections may be important causes of cognitive decline and appear before clinical symptoms. Clinical trial registration-URL: http://www.chictr.org.cn Unique identifier: ChiCTR1900023610. [ABSTRACT FROM AUTHOR]

The association of exosomal RNA profiling and pathogenesis of moyamoya disease (MMD) and intracranial Atherosclerotic disease (ICAD) is unknown. In this study, we investigated the RNA profiles of sEV (small extracellular vesicles)/exosomes in patients with MMD and ICAD. Whole blood samples were collected from 30 individuals, including 10 patients with MMD, 10 patients with ICAD, and 10 healthy individuals. Whole transcriptome analysis was performed using the GeneChip WT Pico Reagent kit. Transcriptional correlation was verified using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The association between functional dysregulation and candidate RNAs was studied in vitro. In total, 1,486 downregulated and 2,405 upregulated RNAs differed significantly between patients with MMD and healthy controls. Differential expression of six circRNAs was detected using qPCR. Among these significantly differentially expressed RNAs, IPO11 and PRMT1 circRNAs were upregulated, whereas CACNA1F circRNA was downregulated. This is the first study showing that the differential expression of exosomal RNAs associated with MMD pathogenesis, such as overexpression of IPO11 and PRMT1 circRNAs, may be related to angiogenesis in MMD. The downregulation of CACNA1F circRNA may be related to vascular occlusion. These results propose the utility of exosomal RNAs as biological markers in MMD. [ABSTRACT FROM AUTHOR]

UCHL5IP is one of the subunits of the haus complex, which is important for microtubule generation, spindle bipolarity and accurate chromosome segregation in Drosophila and human mitotic cells. In this study, the expression and localisation of UCHL5IP were explored, as well as its functions in mouse oocyte meiotic maturation. The results showed that the UCHL5IP protein level was consistent during oocyte maturation and it was localised to the meiotic spindle in MI and MII stages. Knockdown of UCHL5IP led to spindle defects, chromosome misalignment and disruption of γ-tubulin localisation in the spindle poles. These results suggest that UCHL5IP plays critical roles in spindle formation during mouse oocyte meiotic maturation. In mammals, meiosis is a necessary step to produce spermatozoa or oocytes for sexual reproduction, and γ-tubulin localises at the spindle poles to promote microtubule nucleation, which is critical for meiosis procession. In this research, we focussed on the protein UCHL5IP, one of the subunits of augmin, which is important for γ-tubulin localisation in mitosis, to explore its function in oocyte meiotic maturation. Knockdown of UCHL5IP disrupted γ-tubulin localisation and led to chromosome misalignment and spindle defects. Our research reveals the functions of UCHL5IP in mouse oocyte maturation and promotes understanding of the regulation of meiosis. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic carotid artery stenosis (aCAS) impairs haemodynamic and cognitive functions; however, the relationship between these changes and brain network connectivity remains largely unknown. This study aimed to determine the relationship between functional connectivity and neurocognition in patients with aCAS.Methods: We compared functional status in 14 patients with aCAS and 15 healthy controls using resting state functional magnetic resonance imaging sequences. The subjects underwent a full range of neuropsychological tests and a graphical theoretical analysis of their brain networks.Results: Compared with controls, patients with aCAS showed significant decline in neuropsychological functions, particularly short-term memory (word-memory, p = .046 and picture-memory, p = .014). Brain network connectivity was lower in patients with aCAS than in the controls, and the decline of functional connectivity in aCAS patients was mainly concentrated in the left and right inferior frontal gyri, temporal lobe, left cingulate gyrus, and hippocampus. Decreased connectivity between various brain regions was significantly correlated with impaired short-term memory. Patients with aCAS showed cognitive impairment independent of known vascular risk factors for vascular cognitive impairment. The cognitive defects were mainly manifested in the short-term memory of words and pictures.Conclusions: This study is the first of its kind to identify an association between disruption of functional connections in left carotid stenosis and impairment of short-term memory. The findings suggest that alterations in network connectivity may be an essential mechanism underlying cognitive decline in aCAS patients.Clinical Trial Registration-url: Unique identifier: 04/06/2019, ChiCTR1900023610 . [ABSTRACT FROM AUTHOR]

Reciprocal repression of inner cell mass specific factor OCT4 and trophectoderm specific factor CDX2 promotes mouse first lineage segregation. Studies in mouse embryonic stem (ES) cells revealed that they bind to each other's regulatory regions to reciprocally suppress transcription, additionally they form protein complex for mutual antagonism. However, so far the molecular interaction of Oct4 and Cdx2 in other mammal's early embryo is not yet investigated. Here, over-expression of Cdx2 in early porcine embryo showed CDX2 represses Oct4 through neither the transcriptional repression nor forming repressive complex, but promoting OCT4 nuclear export and proteasomal degradation. The results showed novel molecular regulation of CDX2 on Oct4, and provided important clues for clarifying the mechanism of interaction between CDX2 and Oct4 in embryo of mammals other than mouse. [ABSTRACT FROM AUTHOR]