Tauroursodeoxycholic acid (TUDCA) enhanced intracytoplasmic sperm injection (ICSI) embryo developmental competence by ameliorating endoplasmic reticulum (ER) stress and inhibiting apoptosis.

PURPOSE: The objective of this study was to examine the effect of tauroursodeoxycholic acid (TUDCA) on intracytoplasmic sperm injection (ICSI) embryos by evaluating endoplasmic reticulum (ER) stress, apoptosis, and embryo developmental competence in vitro and in vivo. METHODS: ER stress-associated genes and apoptosis-associated genes were measured and apoptosis index was analyzed. Embryo developmental competence was assessed in vitro and in vivo via the inner cell mass (ICM)/trophectoderm (TE) index, pregnancy and implantation rates, and birth rate. RESULTS: The relative mRNA and protein expression of binding immunoglobulin protein (BIP) was significantly higher in the ICSI embryo group without TUDCA treatment (ICSI-C) than in the in vitro fertilization (IVF) group and in the ICSI embryo group with TUDCA treatment (200 µM) (ICSI-T), while TUDCA ameliorated ER stress in ICSI embryos. Embryos in the ICSI-C group showed a higher apoptosis index than those in the IVF group and ICSI-T group, and there was no significant difference between the IVF group and ICSI-T group. TUDCA can significantly improve ICSI embryo developmental competence in vitro and in vivo based on the ICM/TE index, pregnancy and implantation rates, and birth rate. CONCLUSION: ICSI embryos manifested high ER stress and high apoptosis, while TUDCA ameliorated ER stress and reduced apoptosis in ICSI embryos. TUDCA can significantly improve the developmental competence of ICSI embryos in vitro and in vivo. This study provides a new idea for improving the efficiency of ICSI, and it will also have a positive effect on the development of assisted reproduction technologies for humans and other animals.

High-glucose concentrations change DNA methylation levels in human IVM oocytes.

STUDY QUESTION: What are the effects of high-glucose concentrations on DNA methylation of human oocytes? SUMMARY ANSWER: High-glucose concentrations altered DNA methylation levels of Peg3 and Adiponectin in human in vitro maturation oocytes. WHAT IS KNOWN ALREADY: Maternal diabetes has a detrimental influence on oocyte quality including epigenetic modifications, as shown in non-human mammalian species. STUDY DESIGN, SIZE, DURATION: Immature metaphase I (MI) stage oocytes of good quality were retrieved from patients who had normal ovarian potential and who underwent ICSI in the Reproductive Medicine Center of People's Hospital of Zhengzhou University. MI oocytes were cultured in medium with different glucose concentrations (control, 10 mM and 15 mM) in vitro and 48 h later, oocytes with first polar body extrusion were collected to check the DNA methylation levels. PARTICIPANTS/MATERIALS, SETTING, METHODS: MI oocytes underwent in vitro maturation (IVM) at 37°C with 5% mixed gas for 48 h. Then the mature oocytes were treated with bisulfite buffer. Target sequences were amplified using nested or half-nested PCR and the DNA methylation status was tested using combined bisulfite restriction analysis (COBRA) and bisulfite sequencing (BS). MAIN RESULTS AND THE ROLE OF CHANCE: High-glucose concentrations significantly decreased the first polar body extrusion rate. Compared to controls, the DNA methylation levels of Peg3 in human IVM oocytes were significantly higher in 10 mM (P < 0.001) and 15 mM (P < 0.001) concentrations of glucose. But the DNA methylation level of H19 was not affected by high-glucose concentrations in human IVM oocytes. We also found that there was a decrease in DNA methylation levels in the promoter of adiponectin in human IVM oocytes between controls and oocytes exposed to 10 mM glucose (P = 0.028). LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: It is not clear whether the alterations are beneficial or not for the embryo development and offspring health. The effects of high-glucose concentrations on the whole process of oocyte maturation are still not elucidated. Another issue is that the number of oocytes used in this study was limited. WIDER IMPLICATIONS OF THE FINDINGS: This is the first time that the effects of high-glucose concentration on DNA methylation of human oocytes have been elucidated. Our result indicates that in humans, the high risk of chronic diseases in offspring from diabetic mothers may originate from abnormal DNA modifications in oocytes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the fund of National Natural Science Foundation of China (81401198) and Doctor Foundation of Qingdao Agricultural University (1116008).The authors declare that there are no potential conflicts of interest relevant to this article.

ITGAL as a prognostic biomarker correlated with immune infiltrates in melanoma.

This study investigates the relationship between ITGAL expression and immune infiltration, clinical prognosis, and specific types of T cells in melanoma tissue. The findings reveal the key role of ITGAL in melanoma and its potential mechanism of regulating tumor immune infiltrating cells, highlighting its potential as a diagnostic biomarker and therapeutic target for advanced melanoma.

Simultaneous enhancement of elasticity and strength of Al2O3-based ceramics body from cellulose nanocrystals via gel-casting process.

A green gel-casting method was developed by the combination of rod-like cellulose nanocrystals (CNC) and low toxicity monomer N, N-dimethylacrylamide (DMAA), which was proved to be a promising substitute of traditional neurotoxin monomer acrylamide (AM). The hydrophilic nature and homogeneous dispersion of CNC in aqueous suspension ensured the essential compatibility with the hydrosoluble polymerization system, and therefore provided remarkable mechanical enhancement of green body. The bending strength of the green body was highly increased by 68% with the introduction of 0.9 wt‰ CNC. Meanwhile, the fabricated green body exhibited significant improvement in flexibility and elasticity, with the unique bendable and recovery performances after drying treatment at room temperature for 1h. The computer stimulation by the COMSOL Multiphysics confirmed the special mechanical enhancement effect induced by the presence of highly-crystalline and rigid CNC.

Effects of Insulin-like Growth Factor-1 on Development of Somatic Cell Cloned Bovine Embryos.

The aim of this study was to assess the effect of insulin-like growth factor-1 (IGF-1) on the developmental competence of somatic cell nuclear transfer (SCNT) bovine embryos. First, the expression levels of IGF-1 receptor (IGF-1R) and IGF-1 in the oocytes and embryos of different developmental stages were examined. Then the effects of exogenous IGF-1 on the development of SCNT embryos were evaluated both in vitro and in vivo. The results showed that IGF-1 was not expressed in both IVF and SCNT embryos, whereas IGF-1R could be detected throughout the preimplantation stages in both protein and mRNA levels. Also, exogenous IGF-1 had no obvious impact on the developmental competence of IVF embryos. However, it could improve the developmental competence of SCNT embryos in terms of blastocyst developmental rate (31.3% vs. 43.2%, p < 0.05), total cell number (93.0 ± 9.9 vs. 101.0 ± 9.8, p < 0.05), ratio of inner cell mass (ICM) to trophectoderm (TE) (0.29 ± 0.006 vs. 0.39 ± 0.005, p < 0.05), and apoptosis index in day 7 blastocysts (2.5 ± 0.22 vs. 8.7 ± 0.41, p < 0.05) compared to the control group. Although no statistical difference in pregnancy rate and birth rate was observed after embryo transfer, there was an upward tendency in both examined terms in the IGF-1-supplemented group when compared with the control group. In conclusion, the present study showed that supplementing exogenous IGF-1 to the culture medium has an obvious positive effect on the development competence of SCNT embryos.

Effects of oocyte vitrification on epigenetic status in early bovine embryos.

Oocyte cryopreservation has a great impact on subsequent embryonic development. Currently, several studies have primarily focused on the consequences of vitrification and the development potential of cellular structures. This study determined whether oocyte vitrification caused epigenetic instabilities of bovine embryos. The effects of oocyte vitrification on DNA methylation, histone modifications, and putative imprinted genes' expression in early embryos derived by intracytoplasmic sperm injection were examined. Results showed that oocyte vitrification did not affect zygote cleavage rates (67.0% vs. 73.8% control, P > 0.05) but reduced the blastocyst rate (9.6% vs. 23.0%, P < 0.05). The levels of DNA methylation and H3K9me3 in oocytes and early cleavage embryos were lower (P < 0.05) than those in control group, but the level of acH3K9 increased (P < 0.05) in the vitrification group during the early cleavage phases. No differences were observed for DNA methylation, H3K9me3, and acH3K9 in the inner cell mass of blastocysts, whereas decreased levels of DNA methylation and acH3K9 (P < 0.05) existed in TE cells after vitrification. The expression of putative-imprinted genes PEG10, XIST, and KCNQ1O1T was upregulated in blastocysts. These epigenetic abnormalities may be partially explained by altered expression of genes associated with epigenetic regulations. DNA methylation and H3K9 modification suggest that oocyte vitrification may excessively relax the chromosomes of oocytes and early cleavage embryos. In conclusion, these epigenetic indexes could be used as damage markers of oocyte vitrification during early embryonic development, which offers a new insight to assess oocyte vitrification.

Advanced Separators for Lithium-Ion and Lithium-Sulfur Batteries: A Review of Recent Progress.

Li-ion and Li-S batteries find enormous applications in different fields, such as electric vehicles and portable electronics. A separator is an indispensable part of the battery design, which functions as a physical barrier for the electrode as well as an electrolyte reservoir for ionic transport. The properties of the separators directly influence the performance of the batteries. Traditional polyolefin separators showed low thermal stability, poor wettability toward the electrolyte, and inadequate barrier properties to polysulfides. To improve the performance and durability of Li-ion and Li-S batteries, development of advanced separators is required. In this review, we summarize recent progress on the fabrication and application of novel separators, including the functionalized polyolefin separator, polymeric separator, and ceramic separator, for Li-ion and Li-S batteries. The characteristics, advantages, and limitations of these separators are discussed. A brief outlook for the future directions of the research in the separators is also provided.