bims-mamemb 2026-09-20 papers

Sci Rep. 2026 09 15. pii: 28752. [Epub ahead of print]16(1):

First cleavage signatures define a temporal trade-off and predict embryo fitness.

Daphne Norma Crasta, Si Won Lee, Jolene Fredrickson, Theodore Trejo, Nadeem Ghani Khan, Shama Prasada Kabekkodu, Satish Kumar Adiga, Yulian Zhao, Guruprasad Kalthur, Nagarajan Kannan.

Early embryonic development is marked by substantial variability in cleavage dynamics, yet the extent to which first cleavage (FC) features relate to subsequent developmental progression remains incompletely defined. Using parthenogenetic (haploid and diploid) and fertilized embryos from Swiss albino mice, we combined time-lapse imaging with mechanistic analyses to define a novel FC-state grading system (FC-I to FC-IV) based on cleavage symmetry, fragmentation, and correction of the cleavage axis. Aberrant FCs arose from cytoskeletal instability, persistent cytoplasmic bridges, chromosome lagging, and transient nuclear mispositioning. We identified a reproducible inverse relationship between FC duration and subsequent cleavage interval, that predicts blastocyst quality and termed it as 'first cleavage-associated compensatory timing (FACT) relationship'. Haploid parthenogenetic embryos lacked this compensatory timing relationship, which was observed in fertilized embryos and diploid parthenotes, coinciding with markedly reduced developmental progression and competence. Analysis of > 1,100 human embryos revealed analogous FC-states and an inverse relationship between consecutive cleavage intervals that was associated with blastocyst morphology and developmental progression, with no clear association with aneuploidy. These findings position FC-state grading and the FACT relationship as potential non-invasive indicators of early embryo fitness.

Keywords: Blastocyst; Cleavage timing compensation; Cytoskeletal defects; Fertilization; First cleavage; Inner cell mass; Irregular cleavage; Oocyte; Parthenogenesis ; Time-lapse imaging; Totipotency; Trophectoderm

DOI: https://doi.org/10.1038/s41598-026-68288-x

Histochem Cell Biol. 2026 Sep 16. pii: 86. [Epub ahead of print]164(1):

Dnmt3b and Dnmt3l knockdown reduces blastocyst development in early mouse embryos.

Nazlican Bozdemir, Ozgur Cinar, Tugce Oznacar, Ahmet Cevdet Ceylan, Fatma Uysal Cinar.

A one-cell embryo called a zygote develops into a blastocyst through several successive cell divisions and lineage specification, this process is called early embryo development. Both embryonic genome activation (EGA) and the first lineage specification during early embryonic development depend on tightly coordinated epigenomic organization. Regulation of the epigenome is primarily governed by DNA methylation mediated through DNA methyltransferase (Dnmt) enzymes. Dnmt1 is responsible for the maintenance of methylation during cellular division, while Dnmt3a/Dnmt3b enzymes play a role in the establishment of de novo methylation particularly during gametogenesis and early embryo development. Despite its lack of catalytic activity, Dnmt3l functions as a cofactor enhancing Dnmt3a/3b activity. Dnmt3b deficiency results in global hypomethylation and ultimately embryonic lethality. In this study, we aim to elucidate the effect of Dnmt3b and Dnmt3l silencing on early embryo development. For this purpose, our experimental groups were established using an in vitro mouse embryo development model: control, Dnmt3b small interfering RNA (siRNA), Dnmt3l siRNA, and a nontargeting siRNA group. Following gene silencing at the one-cell stage, embryonic developmental competence, the expression pattern of nonsilenced Dnmt enzymes, global DNA methylation levels, and transcriptome profiles were analyzed at the blastocyst stage. Dnmt3b/3l silencing resulted in decreased global DNA methylation and Dnmt1/3a expression, and reduced blastocyst rate. Differentially expressed genes included those involved in X-chromosome inactivation (Xist), transcriptional regulation (Rn7sk), translation (Eef1a1, Eef2), trophoblast development (Hsd3b1), compaction (Gja1), and oxidative phosphorylation (CYTB, COX1, mt-Rnr1). Our findings indicate that siRNA-mediated knockdown of Dnmt3b and Dnmt3l is associated with reduced blastocyst development, impaired embryo quality, and alterations in DNA methylation-related processes during early embryonic development.

Keywords: Blastocyst; DNA methylation; Dnmt3b; Dnmt3l; Early embryo development

DOI: https://doi.org/10.1007/s00418-026-02540-3

Reproduction. 2026 Sep 17. pii: xaag117. [Epub ahead of print]

Mitochondria-Associated Transcription Precedes Oxidative Phosphorylation in Human Embryos.

Andrew J Piasecki, Melissa Franco, Fausto Capelluto, Konstantin Khrapko, Jonathan L Tilly, Dori C Woods.

Mitochondria undergo significant structural and functional changes during human pre-implantation embryogenesis, yet the transcriptional activity of both nuclear-encoded mitochondria-associated genes and mitochondrially transcribed genes across this developmental window remains poorly characterized. While mitochondria are established as the primary energy source for the early embryo, emerging evidence suggests they may also influence lineage specification through epigenetic regulation and metabolite availability. To investigate this, we applied a focused organelle-specific transcriptomic analysis framework, filtering expression data from two publicly available human single-cell RNA sequencing datasets against the MitoCarta 3.0 reference database. The first dataset spanned individual cells from the oocyte through blastocyst stage, and the second compared trophectoderm and inner cell mass cells isolated from blastocysts. Mitochondria-associated gene expression was sufficient to cluster human embryos by developmental stage. A pronounced shift in expression was identified at the 4-cell to 8-cell transition, with 115 unique differentially expressed genes across the two stages immediately following this transition compared to only 5 across the two prior stages. This transcriptional upregulation precedes the known onset of oxidative phosphorylation at approximately the 32-cell stage, suggesting mitochondrial roles in early embryogenesis beyond energy production. Mitochondrially transcribed genes were the primary drivers of clustering in earlier developmental stages, while nuclear-encoded genes drove clustering at the blastocyst stage, and mitochondrial gene expression profiles partially distinguished trophectoderm from inner cell mass lineages. These findings reframe mitochondria as active participants in early human developmental programming, with implications for lineage specification, epigenetic regulation, and the optimization of in vitro embryo culture conditions.

Keywords: Differentiation; Embryogenesis; Mitochondria; Retrograde Signaling; Specification

DOI: https://doi.org/10.1093/reprod/xaag117