Transcriptome profiles of human preimplantation blastocysts related to mosaicism, developmental speed and competence

Clinical and Translational Medicine, Год журнала: 2025, Номер 15(2)

Опубликована: Янв. 24, 2025

Dear Editor, By taking advantage of parallel sequencing genome and transcriptome (G&T-seq),1 we demonstrated the distinct profiles human preimplantation blastocysts in perspectives embryo digital karyotype, developmental speed implantation competence. Our study provided valuable information for further research physiology behind development laid foundation selection from view transcriptome. Preimplantation genetic test aneuploidy (PGT-A) serves as an important invasive method to select euploid embryos. However, even PGT-A cannot guarantee a successful pregnancy,2 almost 50% could not result live birth. It means that there is still big room improve capability besides screening. RNA might have potential assessing competence.3, 4 Here investigated pre-implantation with application G&T-seq (Figure 1A). We verified this biopsied samples 41 donated terms consistency same blastocyst, prediction value aneuploidies by S1), well lineage characteristic inner cell mass (ICM) trophectoderm (TE) S2), indicating clinical safety reproducibility method. unique technology studying chromosomal mosaicism, separate sequencing. In comparisons transcriptomes 28 TE few-cell eight mosaic embryos 17 five euploidies 1B), identified 79 genes upregulated 37 downregulated 1C). Notably, ectoderm primitive endoderm genes, including KLF4, TGFBR1, ITGB5 GATA6, were significantly 1D). Furthermore, mainly enriched embryonic development, stem proliferation, other pathways (Table implying be separation disorder cells inadequately developed trophoblast may contribute adverse pregnancy outcomes Human different speeds. take 5–7 days develop grade stage according Gardner grading system, which allowing biopsy. Clinically, on day 6 or 7 (named D6 D7 blastocyst) are defined growth-retarded lower compared 5 blastocysts. The reason retarded remains clarified. To investigate related blastocyst potential, collected prospectively 105 couples who underwent PGT our reproductive centre 2A Table S2). Totally, 143 (D5 n = 82, 54 7) confirmed G&T-seq, detection efficiency screening was similar conventional NGS period S3). Transcriptionally, these obviously clustered 2B). seemed differentiated more maturely than D5 blastocysts, number expressed average levels marker genes5 S4) increased 6/7 2C,D). look at transcriptional changes normally 5th 7th after fertilization, nine cultured one two days, then sequentially treated form few-cells samples, named D5_D6 D5_D7 samples. characteristics totally but 2E). pseudotime trajectory nearly coincident respectively, roughly arranged fertilization 2F,G). Genes higher expression regulation mitochondrial membrane autophagy, population maintenance, while later (D6/7) amino acid metabolic protein biogenesis process, differentiation, canonical Wnt signalling pathway, placenta steroid biosynthetic process cadherin binding cell-cell adhesion 2H Figure Similar indicate differentiate autonomously clock tick depending morphology This novel finding least partly explain low point cross-talk between endometrium, since they transferred uterus window blastocysts.6, On hand, differentially (DEGs) grow-retarded D6/7 D5_D6/D5_D7 up-regulated DEGs GO regard establishment maintenance polarity S4), most events during early divisions.8 findings delayed-growing dysfunction polarity, consistent publication Wang et al., suggesting arrest share some common mechanism.9 factors affecting originated earlier embryological events, analysis time-lapse imaging shed light issues. Finally, pregnant non-pregnant baseline comparable groups, except ratio corresponding ICM S5). No significant clusters found, overall quite 3A). There DEGs, SOX4, TMSB4X, IFNAR1, C3orf14 CISD2, LRRC4, HTT HES4 group (adjusted p < .05, 3B,C). Moreover, established logistic regression model predicting combining markers characteristics. With use binary analysis, integrated patients' age, endometrial preparation protocol transfer cycle, morphological grade, transferred, highlighted mentioned above. Results revealed HTT, correlated young females S6). verify reported al.,3 due larger sample size good prognosis patients study. conclusion, evaluated transcriptome-wide approach competence found aberrant provide Yanwen Xu Canquan Zhou contributed design work. Song Li, Bing Cai, Chenhui Ding Muhua Lai performed experiments. Jialiu Liu Yan conducted data analysis. Li wrote first draft, revised manuscript. All authors editing reviewing final version supported National Key Research Development Program China (No. 2023YFC2705503 2018YFC1003102), Natural Science Foundation 82071716 81771588) Guangdong Province 201804020087). declare no conflict interest. approved Clinical Laboratory Animal Ethics Committee First Affiliated Hospital Sun Yat-sen University [2020]110), all informed consent. Please note: publisher responsible content functionality any supporting supplied authors. Any queries (other missing content) should directed author article.

Язык: Английский

Concurrent Preimplantation Genetic Testing and Competence Assessment of Human Embryos by Transcriptome Sequencing

Advanced Science, Год журнала: 2024, Номер 11(32)

Опубликована: Июнь 20, 2024

Abstract Preimplantation genetic testing (PGT) can minimize the risk of birth defects. However, accuracy and applicability routine PGT is confounded by uneven genome coverage high allele drop‐out rate from existing single‐cell whole amplification methods. Here, a method to diagnose mutations concurrently evaluate embryo competence leveraging abundant mRNA transcript copies present in trophectoderm cells developed. The feasibility confirmed with 19 donated blastocysts. Next, applied 82 embryos 26 families monogenic defects for simultaneous mutation detection assessment. direct up 95%, which significantly higher than DNA‐based method. Meanwhile, this approach correctly predicted seven out eight (87.5%) that failed implant. Of six are implant successfully, four met such expectations (66.7%). Notably, superior at conditions challenging when using PGT, as detecting pathogenic genes de novo rate, multiple pseudogenes, or an abnormal expansion CAG trinucleotide repeats. Taken together, study establishes RNA‐based also informative assessing implantation competence.

Язык: Английский

Regulation of glucose metabolism: effects on oocyte, preimplantation embryo, assisted reproductive technology and embryonic stem cell

Heliyon, Год журнала: 2024, Номер 10(19), С. e38551 - e38551

Опубликована: Сен. 28, 2024

Язык: Английский