To explore the mechanisms by which abnormal female BMI affects oocyte quality, particularly whether it involves the alteration of gene expression patterns and how these patterns may impact clinical outcomes.In Part 1, we performed a retrospective study to compare the clinical outcomes between the female BMI ≥25 kg/m2 and female BMI ≤20 kg/m2 groups. In Part 2, we performed the transcriptome analyses based on the GSE87201 dataset.In Part 1, among the clinical outcomes, only the grade 1-2 embryo rate at day 3 of ICSI cycles was significantly different between the two BMI groups; the other outcomes were not. In Part 2, compared with the BMI ≤20 kg/m2 group, the oocyte gene expression pattern of the BMI ≥25 kg/m2 group seemed to result in better oocyte tolerance to exogenous stress, such as intracytoplasmic sperm injection (ICSI). It seemed to explain the result of Part 1 that the BMI ≥25 kg/m2 group had better day-3 embryo quality after ICSI than the BMI ≤20 kg/m2 group.Abnormal female BMI affects oocyte quality by altering the gene expression patterns of oocytes. While a female BMI ≥25 kg/m2 is known to have certain detrimental effects on ART, our findings suggest that it can also confer some benefits to oocytes.
Artificial oocyte activation (AOA) is considered an effective method to improve clinical outcomes in patients with some forms of male factor infertility and does not increase the risk of birth defects. However, the effects of AOA on patients with multiple morphological abnormalities of the sperm flagella (MMAF) caused by a DNAH1 mutation are still unknown. To explore the effects, our study analyzed a case with MMAF due to DNAH1 homozygous mutation that underwent testicular sperm extraction (TESE) combined with intracytoplasmic sperm injection (ICSI). The case had 28 MII oocytes. The 28 oocytes were divided randomly and equally into AOA and non-AOA groups. Ionomycin was used for AOA. We compared the clinical outcomes of two groups and selected three blastulation failure embryos from each group for transcriptome analysis (Data can be accessed through GSE216618). Differentially expressed genes (DEGs) were determined with an adjusted p-value <0.05 and a |log2-fold change| ≥1. The comparison of clinical outcomes showed that the two pronuclei (2PN) rate and grade 1-2 embryo rate at day 3 were not significantly different between the two groups. Transcriptome analyses of blastulation failed embryos showed that the use of AOA had potential risks of chromosome structure defects, transcriptional regulation defects, and epigenetic defects. In conclusion, when the case with MMAF due to DNAH1 mutation underwent TESE-ICSI, ionomycin-induced oocyte activation could not improve the clinical outcomes and introduced the risks of chromosome structure defect, transcriptional regulation defect, and epigenetic defect.
Objective: Using Meta-analysis to evaluate the association between Pin1 gene polymorphism at -842 loci and cancer susceptibility. Methods: Pin1, polymorphism, tumor, variant and cancer as key words were used to systematically search for the case-control research on the association between the -842G/C polymorphisms of Pin1 and cancer susceptibility through China National Knowledge Infrastructure (CNKI), Wanfang Data, Embase and PubMed. The time of literatures was up to April 2(nd), 2019. Heterogeneity test, combined risk of cancer with the -842 C allele of Pin1, publication bias test and sensitivity analysis were performed by using Stata 12.0 software. Results: A total of 144 articles were retrieved. According to the inclusion criteria, a total of 11 articles were included (2 Chinese documents and 9 English documents). There were 5 667 cases and 6 120 controls in eligible articles. The heterozygous model showed that Pin1 (-842G/C) polymorphism was associated with cancer susceptibility, and the pooled OR (95%CI) value was 0.78 (0.61, 0.99). Subgroup analysis by cancer type suggested that the Pin1 (-842G/C) polymorphism could significantly decrease the incidence of breast cancer and lung cancer under the heterozygous model (GC vs GG), dominant model (GC+CC vs GG) and allele model (C vs G). The pooled OR (95%CI) values were 0.73 (0.58, 0.92), 0.71 (0.57, 0.89), and 0.73 (0.60, 0.89) in breast cancer and 0.64 (0.52, 0.78), 0.64 (0.53, 0.78), and 0.67 (0.55, 0.80) in lung cancer. The variant -842 C allele could significantly increase the risk of nasopharyngeal carcinoma under the homozygote model (CC vs GG) and recessive model (CC vs GG+GC). The pooled OR (95%CI) values were 2.22 (1.03-4.75) and 2.47 (1.16-5.26). No significant association was observed in squamous cell carcinoma. Conclusion: This Meta-analysis demonstrated that Pin1gene polymorphism at -842 was associated with cancer susceptibility.目的： 采用Meta分析方法探讨Pin1基因-842G/C位点多态性与肿瘤易感性的关联。 方法： 以中文检索词多态性、癌及英文检索词Pin1、polymorphism、tumor、variant、cancer为主题词，系统检索中国知网数据库、万方数据服务平台、Embase和PubMed等数据库截至期为2019年4月2日发表的Pin1基因-842位点多态性与肿瘤易感性的病例-对照研究相关文献。采用Stata 12.0进行Meta分析，进行异质性检验，计算合并风险值并对发表偏倚及敏感性分析进行检验。 结果： 共检索到144篇文献，根据纳入排除标准，共纳入11篇文献（中文文献2篇，英文文献9篇）。累计病例组5 667例，对照组6 120例。Meta分析结果显示，杂合遗传模型中Pin1基因-842位点多态性与肿瘤易感性相关，合并OR（95%CI）值为0.78（0.61~0.99）。肿瘤类型亚组分析结果显示，杂合遗传模型（GC比GG）、显性遗传模型（GC+CC比GG）和等位基因模型（C比G）中Pin1基因-842位C等位基因可能降低乳腺癌、肺癌的发生风险，乳腺癌中OR（95%CI）值分别为0.73（0.58,0.92）、0.71（0.57,0.89）和0.73（0.60,0.89）；肺癌中OR（95%CI）值分别为0.64（0.52，0.78）、0.64（0.53，0.78）、0.67（0.55，0.80）。纯合遗传模型（CC比GG）和隐形遗传模型（CC比GG+GC）中Pin1基因-842位点C等位基因可能增加鼻咽癌的发病风险，其OR（95%CI）值分别为2.22（1.03~4.75）和2.47（1.16~5.26），但未发现其与鳞状细胞癌的发生有关。 结论： Pin1基因-842位点多态性与肿瘤易感性可能相关。.
Context The timing of early cumulus cell removal (ECCR) can be changed within a range. The change has an effect on the multiple pronuclei (MPN) rate and the exposure time of oocytes to sperm waste products. The timing of ECCR effects the outcomes of assisted reproductive technology, however, it is still unclear what time is best for ECCR. Aims To find the best time for ECCR based on clinical outcomes in order to increase the success rate of assisted reproductive technology. Methods A retrospective study was performed. Cycles were categorised into six groups according to the timing of ECCR. The clinical outcomes of these six groups were compared by Kruskal-Wallis test and Pearson X 2 test. Key results The timing of ECCR had a significant effect on the MPN rate, 0PN without cleavage rate and grade 1-2 embryo rate at Day3. Among our six time groups of ECCR, the cumulus cell removal ≤4h post-insemination group had the highest MPN rate and grade 1-2 embryo rate at Day3, and the 5.5h
Abstract Background: Cumulus cells removal 4 h post-insemination has a significantly higher multiple pronuclei (MPN) rate than cumulus cells removal 20 h post-insemination. And, cumulus cells removal 6 h post-insemination has a significantly lower MPN rate than cumulus cells removal 20 h post-insemination. However, it remains unclear whether the different timings of early cumulus cells removal, such as the timings of 4, 5 and 6 h post-insemination, have significantly different MPN rates. Methods: This was a retrospective study. The included cycles were early cumulus cells removal cycles (n=752) at our center from January 2015 to August 2020. The included cycles were divided into two groups according to whether MPN exist (MPN=0% and MPN>0%). The patient and cycle stimulation characteristics of the two groups were compared. Binary logistic regression was performed to investigate the correlation between the timing of early cumulus cells removal and MPN. The cohort study was also performed to compare the patient characteristics, cycle stimulation characteristics, fertilization outcomes, and cultivation outcomes. Results: In the population of our study, the timing of early cumulus cells removal had a significant effect on the MPN. The cumulus cells removal ≤4 h post-insemination group had a high MPN rate, and the 5.5<time≤6 h group had a high fertilization failure rate. However, 2PN rate was not significantly different among the different timings of early cumulus cells removal. In addition, the ≤4 h post-insemination group had a high grade 1–2 embryo rate at day 3. Conclusion(s): Even if all the timings of cumulus cells removal are early, the different timings of early cumulus cells removal still have a significant effect on the MPN.
Objective To assess the application value of mapping allele with resolved carrier status (MaReCs) technique for preimplantation genetic testing (PGT). Methods The characteristics of MaReCs for PGT and outcome of patients were retrospectively analyzed. Results Compared with those who could not use the technique, carriers who have used the MaReCs technique were younger, had significantly higher level of anti-Mullerian hormone, more antral follicles, occytes, mature occytes, biopsied embryos and euploid embryos, and lower risks for de novo chromosomal abnormality (P 0.05). Carriers undergoing MaReCs test could preferentially select embryos with normal chromosome structures for the transfer. Conclusion Application of MaReCs has a prerequisite for having a minimum number of occytes and biopsied embryos and using discarded embryos sometimes. MaReCs is efficient for the detection of carrier status of embryos and attaining higher rate of pregnancy and live birth, which can significantly improve the outcome for couples carrying chromosomal translocations.
AbstractModulation of the interaction between U1 snRNP and the 5′ splice site (5′ss) is a key event that governs 5′ss recognition and spliceosome assembly. Using the methylene blue-mediated cross-linking method (Z. R. Liu, A. M. Wilkie, M. J. Clemens, and C. W. Smith, RNA 2: 611-621, 1996), a 65-kDa protein (p65) was shown to interact with the U1-5′ss duplex during spliceosome assembly (Z. R. Liu, B. Sargueil, and C. W. Smith, Mol. Cell. Biol. 18: 6910-6920, 1998). In this report, p65 was identified as p68 RNA helicase and shown to be essential for in vitro pre-mRNA splicing. Depletion of endogenous p68 RNA helicase does not affect the loading of the U1 snRNP to the 5′ss during early stage of splicing. However, dissociation of the U1 from the 5′ss is largely inhibited. The data suggest that p68 RNA helicase functions in destabilizing the U1-5′ss interactions. Furthermore, depletion of p68 RNA helicase arrested spliceosome assembly at the prespliceosome stage, suggesting that p68 may play a role in the transition from prespliceosome to spliceosome. I thank Frances Fuller-Pace for providing hybridoma cells for the antibody PAb204 and Roger Bridgeman for antibody PAb204 production. I am also grateful to D. L. Peterson for the HCV-NS3 expression vector. I thank Chris W. J. Smith, Mariano A. Garcia-Blanco, Jenny Yang, and Jan Szechi for detailed critical comments on the manuscript.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)