Biology subjects

Lacour, P.

Publications and source records attributed to Lacour, P..

3 recordsLinked to original sources

bioRxiv2023

Superovulation and aging perturb oocyte-granulosa cell communication

In vitro fertilization has been developed to overcome reduced fertility, which is increasingly due to a decline in reproductive cell quality during aging. Here, we quantitatively investigated the interplay between superovulation and aging in mouse oocytes and their paired granulosa cells using newly adapted isolation techniques. We tested the hypothesis that superovulation disrupts oocyte maturation, revealing the key intercellular communication pathways dysregulated by forced hormonal stimulation. We further demonstrated that granulosa cell transcriptional markers can prospectively predict an associated oocytes early developmental potential. By using naturally ovulated old mice as a non-stimulated reference, we showed that aging and superovulation dysregulate similar genes and interact with each other. By comparing mice and human transcriptional responses of granulosa cells, we found that age-related dysregulation of hormonal responses and cell cycle pathways was shared, though substantial divergence exists in other pathways. HighlightsO_LISuperovulation perturbs cumulus-oocyte communication C_LIO_LIGranulosa cell transcription predicts superovulated oocyte quality C_LIO_LISuperovulation and aging non-additively perturb similar sets of genes C_LI

developmental biology↗

bioRxiv2022

The function and decline of the female reproductive tract at single-cell resolution

The female reproductive tract (FRT) undergoes extensive remodeling during each reproductive cycle, regulated by systemic changes in sex hormones. Whether this recurrent remodeling influences a specific organs aging trajectory is unknown. To address this, we systematically characterized at single-cell resolution the morphological and transcriptional changes that occur in ovary, oviduct, uterus, cervix, and vagina at each phase of the mouse estrus cycle, during decidualization, and into aging. Transcriptional and cell-to-cell communication networks in estrus cycle and aging are enriched for ECM reorganization and inflammation, two essential components of FRT remodeling. We directly link the organ-specific level of these two processes over reproductive lifespan with the gradual, age-related development of fibrosis and chronic inflammation. Our data represent a comprehensive atlas of the FRT lifespan, revealing pathological consequences of incomplete resolution of recurrent inflammation and tissue repair.

genomics↗

bioRxiv2022

CTCF, BEAF-32 and CP190 are not required for the initial establishment of TADs in early Drosophila embryos, but have locus specific roles

The boundaries of Topologically-Associating Domains (TADs) are delimited by insulators and active promoters, however how they are initially established during embryogenesis remains unclear. Here, we examined this during the first hours of Drosophila embryogenesis. DNA-FISH on individual embryos indicates that domains form during zygotic genome activation (ZGA), but have extensive cell-to-cell heterogeneity compared to later stages. Most newly formed boundaries are occupied by combinations of CTCF, BEAF- 32 and/or CP190. Depleting each insulator from chromatin revealed that TADs can still establish during ZGA, although with lower insulation, with particular boundaries being more sensitive. Some weakened boundaries have aberrant gene expression, however the majority of mis-expressed genes have no obvious relationship to changes in domain-boundary insulation. Deletion of an active promoter (thereby blocking transcription) at one boundary had a greater impact compared to deleting the insulator-bound region itself. These results suggest cross-talk between insulators and transcription might reinforce domain formation during embryogenesis.

developmental biology↗