Biology subjects

Bridi, A.

Publications and source records attributed to Bridi, A..

4 recordsLinked to original sources

bioRxiv2025

Mammal placental phenotypes are predictable from microRNA repertoires.

Similar placental morphologies evolved multiple times independently in the history of mammal evolution1,2. Yet the genetic architecture that repeatedly guides distinct mammal lineages towards similar complex placental phenotypes has remained elusive. MicroRNAs (miRNAs), despite their diversity in mammals3-7 and known roles as developmental regulators8-10, remain under-examined as drivers of morphological innovation. We identified presence-absence patterns for 429 miRNA gene families across 398 mammalian genomes and discovered that placental phenotype is highly predictable from genomic miRNA repertoires (classification accuracy 74.5-95.8%). We identified 42 miRNA gene families significantly associated with placentation type, whose gene targets are enriched for developmental processes. Notably, convergent placental morphologies consistently involve identical miRNA families, revealing that evolution of this trait is constrained to predictable genetic pathways. We demonstrate that MIR-11986, uniquely associated with cotyledonary placentation, has tissue-specific expression in key reproductive tissues. MiRNA-mediated regulation therefore constrains placental morphological diversification into reproducible programs, offering insights into how genetic architecture shapes the predictability of convergent evolution. This striking pattern reveals a fundamental principle of evolution: that the miRNA regulatory networks available to control and guide complex placental morphological innovation are constrained and predictable.

genomics↗

bioRxiv2023

Artificial environment impact: O2 concentration changes between IVM and IVF alter embryo production, metabolism, and epigenetic marks

Creating an optimal in vitro cell culture environment requires careful simulation of all critical components, especially the gaseous atmosphere. Although it is well-documented that embryonic culture under low oxygen tension promotes embryonic development, little is known about the effect of changes in in vitro maturation (IVM) and fertilization (IVF) on the epigenome. This study explores the role of oxygen tension variation in the early stages of in vitro production of bovine embryos and its impact on oxidative stress and epigenetic remodeling. We initially validated our system by scrutinizing the epigenetic effects on bovine fibroblasts. We observed that cell cultures under 20% O2 exhibited reduced H3K9me2 levels in early passages, which stabilized with prolonged cultivation and elevated gene expression of HIF2a and KDM5C. Our results reveal that oocytes maturing in 20% O2 environments have heightened levels of reactive oxygen species (ROS) and glutathione (GSH), whereas blastocyst embryos maturing under reduced oxygen tension exhibit increased oxidative stress markers (NRF2, SOD1, SOD2), with upregulated transcripts observed in epigenetic remodelers (KDM5A, TET1). Elevated O2 levels in both IVM and IVF processes showcase improved embryo production. Maintaining consistent O2 levels at either 5% or 20% between IVM and IVF results in heightened GSH, reduced ROS, and increased levels of H3K9me2/3 in embryos. Finally, distinct DNA methylation patterns emerge, indicating higher levels in groups matured under low O2 tension and increased DNA hydroxymethylation in groups fertilized under low O2 tension. In conclusion, our comprehensive investigation underscores the critical role of oxygen concentration in shaping the epigenetic landscape during the early stages of in vitro culture. These findings provide valuable insights for optimizing conditions in assisted reproductive technologies.

developmental biology↗

bioRxiv2023

Biosensor capability of the endometrium is mediated in part, by altered miRNA cargo from conceptus-derived extracellular vesicles.

We tested the hypothesis that the biosensor capability of the endometrium is mediated in part, by the effect of different cargo contained in the extracellular vesicles secreted by the conceptus during the peri-implantation period of pregnancy. We transferred Bos taurus taurus embryos of different origin: In vivo (high developmental potential (IV)), in vitro (intermediate developmental potential (IVF)), or cloned (low developmental potential (NT)), into Bos taurus indicus recipients. Extracellular vesicles (EVs) recovered from Day 16 conceptus conditioned medium were characterized and their microRNA (miRNA) cargo sequenced alongside RNA sequencing of their respective endometria. There were substantial differences in the endometrial response to in vivo Vs in vitro and in vivo Vs cloned conceptuses (1153 and 334DEGs respectively) with limited differences between in vitro Vs cloned conceptuses (36 DEGs). miRNA cargo was similar between all three groups (426 common cargo) differences between in vivo and cloned (8 miRNAs), and in vivo and in vitro (6 miRNAs) observed. Treatment of endometrial epithelial cells with mimic or inhibitors for miR-128 and miR-1298 changes to the proteomic content of target cells (96, and 85 respectively) of which mRNAs are altered in the endometrium in vivo (PLXDC2, COPG1, HSPA12A, MCM5, TBL1XR1, and TTF). In conclusion, we have determined that the biosensor capability of the endometrium is mediated in part, by its response to different EVs miRNA cargo produced by the conceptus during the peri-implantation period of pregnancy. SIGNIFICANCE STATEMENTDuring the peri-implantation period of pregnancy in mammals, the endometrium acts as a biosensor for the developmental competency of the embryo. However, the mechanism by which biosensor capability of the endometrium is established, remains elusive. In this study, we show that embryos of different developmental competencies have distinct microRNA cargo contained in their extracellular vesicles (EVs). Exposure of the endometrium to these conceptuses alters the transcriptional response of the endometrium during the process of pregnancy recognition. This differential response is mediated in part, by the delivery and action of the these differentially abundant microRNAs into EVs. Here we propose differences in EV-mediated miRNA cargo are responsible in part for this biosensor capability of the endometrium.

developmental biology↗

bioRxiv2019

Catalytic inhibition of H3K9me2 writers disturbs epigenetic marks during bovine nuclear reprogramming.

Orchestrated events, including extensive changes in epigenetic marks, allow a somatic nucleus to become totipotent after transfer into an oocyte, a process termed nuclear reprogramming. Recently, several strategies have been applied in order to improve reprogramming efficiency, mainly focused on removing repressive epigenetic marks such as histone methylation from the somatic nucleus. Herein we used the specific and non-toxic chemical probe UNC0638 to inhibit the catalytic activity of the histone metyltransferases EHMT1 and EHMT2. Either the donor cell (before reconstruction) or the early embryo was exposed to the probe to assess its effect on developmental rates and epigenetic marks. First, we showed that the treatment of bovine fibroblasts with UNC0638 did mitigate the levels of H3K9me2. Moreover, H3K9me2 levels were decreased in cloned embryos regardless of treating either donor cells or early embryos with UNC0638. Additional epigenetic marks such as H3K9me3, 5mC, and 5hmC were also affected by the UNC0638 treatment. Therefore, the use of UNC0638 did diminish the levels of H3K9me2 and H3K9me3 in SCNT-derived blastocysts, but this was unable to improve their preimplantation development. These results indicate that the specific reduction of H3K9me2 by inhibiting EHMT1/2 causes diverse modifications to the chromatin during early development, suggesting an intense epigenetic crosstalk during nuclear reprogramming.

developmental biology↗