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Jouneau, A.

Publications and source records attributed to Jouneau, A..

4 recordsLinked to original sources

Short-term exposure to Cook, Vitrolife, and KSOM media shapes early calcium oscillations in ICSI-fertilized mouse oocytes and impacts adult phenotype

PurposeThe influence of culture media used during in vitro fertilization (IVF) on offspring phenotype remains controversial. However, specific effects of short exposure time after fertilization remain underexplored. By evaluating Ca2+ oscillations as a readout of the first response of eggs to their microenvironment, we aim to investigate if early differences correlate with later adult phenotypes. MethodsOocytes fertilized by ICSI were cultured for four hours in three different media (Cook and Vitrolife, used in human IVF, and KSOM, used for mouse embryos). They were either measured for Ca2+ oscillations or transferred into pseudo-pregnant females. After birth, growth curves of pups were measured up to adulthood and various organs weighed. ResultsCulture media significantly modulate Ca2+ oscillations during oocyte activation. ICSI-fertilized oocytes cultured in Cook and Vitrolife exhibited fewer oscillations, lower frequency, and reduced variability compared to KSOM. These early differences correlated with long-term developmental outcomes: females from Cook and Vitrolife cultures were heavier throughout growth and had larger adult organ sizes compared to those from KSOM. ConclusionsBrief exposure to media immediately after ICSI shapes Ca2+ dynamics and adult phenotypes. Optimizing embryo culture protocols in assisted reproductive technologies may improve IVF outcomes by modulating metabolic pathways linked to development.

developmental biology↗

ZBTB24 is a conserved multifaceted transcription factor at genes and centromeres that governs the DNA methylation state and expression of satellite repeats

Since its discovery as an Immunodeficiency with Centromeric instability and Facial anomalies syndrome-causative gene, ZBTB24 has emerged as a key player in DNA methylation, immunity and development. By extensively analyzing ZBTB24 genomic functions in ICF-relevant mouse and human cellular models, we revealed here its multiple facets as a transcription factor, with key roles in immune response-related genes expression and also in early embryonic development. Using a constitutive Zbtb24 ICF-like mutant and an auxin-inducible degron system in mouse embryonic stem cells, we showed that ZBTB24 is recruited to centromeric satellite DNA where it is required to establish the correct DNA methylation patterns through the recruitment of DNMT3B. Thus, our results further revealed an essential role for ZBTB24 at human and mouse centromeric satellite arrays, as a transcriptional repressor. Together, we unveiled unprecedented functions of ZBTB24 at human and mouse centromeres by directly controlling DNA methylation and transcription of the underlying tandem satellite repeats.

genomics↗

Ablation of ZC3H11A causes early embryonic lethality and dysregulation of metabolic processes

ZC3H11A is a stress-induced mRNA binding protein required for efficient growth of nuclear-replicating viruses, while being dispensable for the viability of cultured human cells. The cellular functions of ZC3H11A during embryo development are unknown. Here we report the generation and phenotypic characterization of Zc3h11a knock-out mice. Heterozygous null Zc3h11a mice were born at the expected frequency without distinguishable phenotypic differences compared with wild-type. In contrast, homozygous null Zc3h11a mice were missing, indicating that Zc3h11a is crucial for embryonic viability and survival. Zc3h11a-/- embryos were detected at the expected Mendelian ratios up to late preimplantation stage (E4.5). However, phenotypic characterization at E6.5 revealed degeneration of Zc3h11a-/- embryos, indicating developmental defects around the time of implantation. Transcriptomic analyses documented a dysregulation of glycolysis and fatty acid metabolic pathways in Zc3h11a-/- embryos at E4.5. Proteomic analysis indicated a tight interaction between ZC3H11A and mRNA-export proteins in embryonic stem cells. Furthermore, CLIP-seq analysis demonstrated that ZC3H11A binds a subset of mRNA transcripts that are critical for metabolic regulation of embryonic cells. Altogether, the results show that ZC3H11A is participating in export and post-transcriptional regulation of selected mRNA transcripts required to maintain metabolic processes in embryonic cells. While ZC3H11A is essential for the viability of the early mouse embryo, inactivation of Zc3h11a expression in adult tissues using a conditional knock-out did not lead to obvious phenotypic defects.

cell biology↗

rDNA nascent transcripts promote a unique spatial organization during mouse early development

During the first cell cycles of the early development, the chromatin of the embryo is highly reprogrammed alongside that embryonic genome starts its own transcription. The spatial organization of the genome is a major process that contributes to regulating gene transcription in time and space, however, it is poorly studied in the context of early embryos. To study the cause and effect link between transcription and spatial organization in embryos, we focused on the ribosomal genes, that are first silent and begin to transcribe during the 2-cell stage in mouse. We demonstrated that ribosomal sequences are spatially organized in a very peculiar manner from the 2-cell to the 16-cell stage with transcription and processing of ribosomal RNAs excluding mutually. Using drugs inhibiting the RNA polymerase I, we show that this organization, totally different from somatic cells, depends on an active transcription of ribosomal genes and induces a unique chromatin environment that favors major satellite sequences transcription after the 4-cell stage.

cell biology↗