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Purpose: Providing feasible preimplantation genetic testing strategies for monogenic disorders (PGT-M) for prevention and control of genetic cancers. Methods: Inclusion of families with a specific pathogenic mutation or a clear family history of genetic cancers. Identification of the distribution of hereditary cancer-related mutations in families through genetic testing. After a series of assisted reproductive measures such as down-regulation, stimulation, egg retrieval, and in vitro fertilization, a biopsy of trophectoderm cells from a blastocyst was performed for single-cell level whole-genome amplification (WGA). Then, the detection of chromosomal aneuploidies was performed by karyomapping. Construction of a haplotype-based linkage analysis to determine whether the embryo carries the mutation. Meanwhile, we performed CNV testing. Finally, embryos can be selected for transfer, and the results will be verified in 18–22 weeks after pregnancy. Results: Six couples with a total of 7 cycles were included in our study. Except for cycle 1 of case 5 which did not result in a transferable embryo, the remaining 6 cycles produced transferable embryos and had a successful pregnancy. Four couples have had amniotic fluid tests to confirm that the fetus does not carry the mutation, while 1 couple was not tested due to insufficient pregnancy weeks. And the remaining couples had to induce labor due to fetal megacystis during pregnancy. Conclusion: Our strategy has been proven to be feasible. It can effectively prevent transmission of hereditary cancer-related mutations to offspring during the prenatal stage. [ABSTRACT FROM AUTHOR]

Purpose: Currently, owing to the limitations of high-throughput sequencing depth and the allele dropout caused by the whole-genome amplification, detection of chromosomal variants in embryos with CNVs <5 Mb is unsatisfactory at the single-cell level using only conventional sequencing methods. Therefore, here we aimed to use a strategy of preimplantation genetic testing for monogenic (PGT-M) to compensate for the shortcomings of conventional sequencing methods. The purpose of this study is to report the effectiveness of haplotype linkage analysis by karyomapping for preimplantation diagnosis microdeletion diseases. Methods: Six couples carrying chromosomal microdeletions associated with X-linked ichthyosis were recruited, and all couples entered the PGT process. Multiple displacement amplification (MDA) method was used to amplify the whole-genome DNA of trophectoderm cells. Then karyomapping based on single nucleotide polymorphism (SNP) was used for haplotype linkage analysis to detect alleles carrying microdeletions, and CNVs of embryos were identified to determine euploid identity. Amniotic fluid tests were performed in the second trimester to verify the PGT-M results. Results: All couples were tested for chromosomal microdeletions, with deletion fragments ranging in size from 1.60 to 1.73 Mb, and one partner in each couple did not carry the microdeletion. Three couples successfully underwent PGT-M assisted conception and obtained healthy live births. Conclusion: This study shows that haplotype linkage analysis by karyomapping could effectively detect the carrier status of embryos with microdeletions at the single-cell level. This approach may be applied to the preimplantation diagnosis of various chromosomal microvariation diseases. [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to investigate the relationship between elevated maternal body mass index (BMI) and foetal chromosomal aberrations by performing single-nucleotide polymorphism (SNP) array-based genetic testing on products of conception (POC). Methods: We retrospectively reviewed the data for 1068 assisted reproductive technology (ART)-conceived POC originated from 1068 patients with early spontaneous miscarriage. First, all types of chromosomal abnormalities were defined. Then, the baseline characteristics, including maternal age, BMI, thyroid-stimulating hormone (TSH), gestational age, fertilization method, reasons for fertility treatment, embryo transfer (ET) cycle, stage of embryo development and the embryo morphology grade, were compared between chromosomally normal and abnormal POC groups. Finally, a multivariate logistic regression model was used to analyse various factors affecting the foetal chromosomal abnormality rate. Results: The SNP array results showed that 45.3% (484/1068) of POC were chromosomally normal and that 54.7% (584/1068) of POC presented chromosomal abnormalities. Of these 584 chromosomally abnormal POC, 388 (66.4%) were trisomy, 42 (7.2%) had a monosomy, 68 (11.6%) were found with segmental aneuploidy, 46 (7.9%) were mosaic, 28 (4.8%) were identified as polyploidy and 12 (2.1%) were euploid samples with uniparental disomy (UPD). Multivariate logistic regression results showed that the risk of miscarrying chromosomally abnormal POC increased 1.424-fold in women with normal BMI compared to women with an elevated BMI (≥ 25 kg/m2) (OR = 1.424, 95% CI = 1.074–1.888, p = 0.014). Conclusion: Women with an elevated BMI (≥ 25 kg/m2) are more likely to miscarry chromosomally normal POC. [ABSTRACT FROM AUTHOR]

Purpose: The preimplantation genetic testing for monogenic defects (PGT-M) is a beneficial strategy for the patients suffering from a Mendelian disease, which could protect their offspring from inheriting the disease. The purpose of this study is to report the effectiveness of PGT-M based on karyomapping for three cases of dynamic mutation diseases with trinucleotide repeat expansion. Methods: PGT-M was carried out on three couples, whose family members were diagnosed with Huntington's disease or spinocerebellar ataxias 2 or 12. The whole genome amplification was obtained using the multiple displacement amplification (MDA) method. Then, karyomapping was performed to detect the allele that is carrying the trinucleotide repeat expansion using single nucleotide polymorphism (SNP) linkage analyses, and the copy number variations (CNVs) of the embryos were also identified. Prenatal diagnosis was performed to validate the accuracy of PGT-M. Results: PGT-M was successfully performed on the three couples, and they accepted the transfers of euploid blastocysts without the relevant pathogenic allele. The clinical pregnancies were acquired and the prenatal diagnosis of the three families confirmed the effectiveness of karyomapping. The three born babies were healthy and free of the pathogenic alleles HTT, ATXN2, or PPP2R2B corresponding to Huntington's disease, spinocerebellar ataxias 2 or 12, respectively. Conclusion: This study shows that karyomapping is a highly powerful and efficient approach for dynamic mutation detection in preimplantation embryos. In this work, we first report the birth of healthy babies that are free of the pathogenic gene for dynamic mutation diseases in patients receiving PGT-M by karyomapping. [ABSTRACT FROM AUTHOR]

In recent years, wearable and stretchable electronic devices have attracted great research interest and effort due to their promising applications in electronic skin, wearable health monitoring, human–machine interactions and so on. However, it still remains a great challenge to fabricate highly stretchable and wearable devices with excellent breathability, mechanical robustness and laundering durability. Herein, we fabricated a highly stretchable and breathable textile strain sensor based on conductive polyester fabric (CPF) with weft-knitted structure by chemically growing conductive and transparent Al-doped ZnO (AZO) element via atomic layer deposition (ALD). The CPF strain sensor demonstrates captivating performance, including high stretchability (up to 130%) and long-term stability (3000 cycles), as well as a distinct negative resistance variation with increasing strain owing to its weft-knitted structure. Most importantly, due to the formation of chemical interactions between textiles and AZO films during ALD process, the CPF strain sensor exhibits excellent mechanical robustness and laundering durability under reciprocating rubbing (50 kPa load pressure, 30 cycles), washing (500 r/min for 10 cycles, 200 min) and light fastness (accelerated light aging test for 7 days), thus allowing the fabrication of breathable and comfortable wearable sensor without elastomer encapsulation. Based on its admirable performances, the CPF strain sensor can be easily knitted or sewed on garments or attached on human skin directly for tracking both large and subtle human motions, revealing its numerous prospects in wearable electronics, intelligent robotics and other fields. [ABSTRACT FROM AUTHOR]

Single-material flexible actuators that can produce non-uniform deformation in response to external stimuli have attracted considerable interests due to their facile fabrication process and excellent actuation behavior. However, the recognition of actuation state with easily perceived and detectable signal is still a challenge. In this paper, we report an actuator behavior of single-material inverse opal photonic crystal films, which are in response to a variety of solvents based on swelling/de-swelling process. The actuator exhibits improved responsiveness due to the enhanced mass transport of solvent molecules in periodic inverse opal with macroporous structure. Especially, peaks in reflective spectra and corresponding structure colors are obviously changed, providing a simple and effective optical technology for optical recognition of micro-locomotion. Based on the above characteristics, we demonstrate the potential applications of this photonic crystal actuator as solvent-driven gripper, walking device and rolling motor, showing great promise in advanced soft robot for many important intelligent areas. [ABSTRACT FROM AUTHOR]

Upon fertilization, drastic chromatin reorganization occurs during preimplantation development [1]. However, the global chromatin landscape and its molecular dynamics in this period remain largely unexplored in humans. Here we investigate chromatin states in human preimplantation development using an improved assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) [2]. We find widespread accessible chromatin regions in early human embryos that overlap extensively with putative cis-regulatory sequences and transposable elements. Integrative analyses show both conservation and divergence in regulatory circuitry between human and mouse early development, and between human pluripotency in vivo and human embryonic stem cells. In addition, we find widespread open chromatin regions before zygotic genome activation (ZGA). The accessible chromatin loci are readily found at CpG-rich promoters. Unexpectedly, many others reside in distal regions that overlap with DNA hypomethylated domains in human oocytes and are enriched for transcription factor-binding sites. A large portion of these regions then become inaccessible after ZGA in a transcription-dependent manner. Notably, such extensive chromatin reorganization during ZGA is conserved in mice and correlates with the reprogramming of the non-canonical histone mark H3K4me3, which is uniquely linked to genome silencing [3]- [5]. Taken together, these data not only reveal a conserved principle that underlies the chromatin transition during mammalian ZGA, but also help to advance our understanding of epigenetic reprogramming during human early development and in vitro fertilization. By applying an optimized ATAC-seq protocol to human early embryos, distinct accessible chromatin landscapes are found before and after zygotic genome activation, revealing a marked epigenetic transition during zygotic genome activation and putative regulatory elements wiring human early development. [ABSTRACT FROM AUTHOR]

Purpose: We reviewed the influence of dehydroepiandrosterone (DHEA) supplementation in patients with poor ovarian response (POR) undergoing in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI). Methods: We searched Embase, MEDLINE, PubMed, and the Cochrane Library (1980-2015) for relevant papers and used the Newcastle-Ottawa Scale scoring system to evaluate study quality. Dichotomous data were expressed as pooled relative risk (RR) estimates with fixed or random effect models. Continuous variables were expressed as the weighted mean difference (WMD). All data were analyzed using Revman Software v. 5 and are shown with 95 % confidence intervals (CI). Results: Twenty-one studies met the inclusion criteria. DHEA pretreatment increased the clinical pregnancy rate (RR 1.53, 95 % CI 1.25-1.86), live birth rate (RR 1.87, 95 % CI 1.22-2.88), implantation rate (RR 1.56, 95 % CI 1.20-2.01), and antral follicle count (WMD 0.4, 95 % CI 0.14 to 0.66) while reducing miscarriages (RR 0.50, 95 % CI 0.27-0.90). After subgroup analysis, oocyte numbers and anti-Müllerian hormone levels were also enhanced after DHEA treatment. However, the endometrial thickness and estradiol levels on the day of injecting hCG to induce ovulation were similar between the DHEA supplementation groups and controls. Conclusions: Based on the limited available evidence, DHEA supplementation seems to improve ovarian reserves and IVF/ICSI outcome in patients with POR. Further research is required to clarify the effect of DHEA exposure in assisted reproduction technology. [ABSTRACT FROM AUTHOR]

In this Letter, the ‘Open chromatin’ label in Fig. 4a should have been centred above the first three columns, and the black horizontal line underneath the label should have been removed. In addition, there should have been a vertical black line between the last two sets of panels for consistency. Minor changes have also been made to Fig. 1 and to the legend of Fig. 3. These errrors have been corrected online, and see Supplementary Information to the accompanying Amendment for the original Fig. 4. [ABSTRACT FROM AUTHOR]

Uniparental disomy (UPD) has been shown to be rare in human normal blastocysts, but its frequency in discarded morphologically abnormal embryos and its relevance to embryonic self-correction of aneuploid remains unknown. The aim of this study was to detect UPD in discarded morphologically abnormal embryos. Both discarded morphologically abnormal embryos, including zero-pronuclear zygotes (0PN), one-pronuclear zygotes (1PN), three-pronuclear zygotes (3PN) and 2PN embryos scored as low development potential were cultured into blastocysts then underwent trophectoderm biopsy. Genome-wide UPD screening of the trophectoderm of 241 discarded morphologically abnormal embryo sourced blastocysts showed that UPD occurred in nine embryos. Five embryos exhibited UPDs with euploid chromosomes, and four displayed UPDs with chromosomal aneuploid. The percentage of UPDs among the morphologically abnormal sourced blastocysts was 3.73%, which is significant higher than the percentage observed in normal blastocysts. The frequency of UPD in 3PN-sourced blastocysts was 7.69%, which is significantly higher than that in normal blastocysts. This study provides the first systematic genome-wide profile of UPD in discarded morphologically abnormal embryos. Our results indicated that UPD may be a common phenomenon in discarded morphologically abnormal embryos and may be relevant to human embryonic self-correction. [ABSTRACT FROM AUTHOR]