Biology subjects

Plante, I.

Publications and source records attributed to Plante, I..

5 recordsLinked to original sources

bioRxiv2026

Late gestational exposure to flutamide alters stromal composition and immune landscape in the rat mammary gland during pre-puberty, peri-puberty, and adulthood

Perinatal development of the mammary gland is regulated by hormonal signals that influence cell proliferation, extracellular matrix remodeling, immune cell recruitment, and intracellular signaling. While the role of estrogen in mammary gland development is well established, the impact of androgens remains less understood. To address this gap, we inhibited androgen signaling in utero using the anti-androgen flutamide (FLU) and investigated the effects on mammary gland development in rats. Using an integrative strategy combining histology, transcriptomics, lipidomics, cytokine profiling, and high-resolution imaging, mammary tissue were analyzed at pre-puberty (postnatal days (PND) 21), peri-puberty (PND46), and adulthood (PND9O). FLU exposure induced subtle, yet significant, alterations in mammary morphology and molecular signatures. At PND2l, the FLU exposed group exhibited an increased number of adipocytes with reduced size. Transcriptomic analysis revealed differentially expressed genes at PND2l and enrichment in pathways related to androgen response and immune signaling, but minimal changes at later developmental stages. Lipidomic profiling showed transient disruption in long-chain fatty acid composition at early developmental stages. Cytokine profiling revealed a reduced adaptive immune response at PND46 and PND9O, and second harmonic generation imaging demonstrated changes in collagen fiber orientation and density across all developmental stages. These data indicate that prenatal androgen signaling is essential for proper stromal development and the establishment of early transcriptional networks in the mammary gland, with only minor long-term effects on glandular architecture in adult nulliparous females.

pharmacology and toxicology↗

bioRxiv2025

An in utero exposure to the synthetic estrogen diethylstilbestrol affects the fat pad composition in post-natal mammary glands

In utero exposure to the synthetic estrogen diethylstilbestrol (DES) has been linked to developmental abnormalities and elevated breast cancer risk in adulthood in human and rodent models. While the impact of DES on the mammary epithelium has been thoroughly investigated, its effect on the other cell types of the mammary gland remains understudied. Here, given that the mammary gland development is strongly associated with its microenvironment, we aimed to investigate how in utero DES exposure alters the mammary glands stromal and immune function across key developmental stages. To achieve this aim, timed-pregnant rats were gavaged daily with DES or vehicle from gestation days 16-21, and female offspring mammary glands were analyzed at pre-puberty (postnatal day 21 (PDN21)), puberty (PND46), and adulthood (PND90). We assessed morphological and extracellular matrix changes, performed transcriptomic cell-type enrichment analysis, measured cytokine expression, and quantified immune cell populations. DES-exposed mammary glands exhibited pronounced stromal remodeling, including increased collagen deposition and orientation by adulthood. Gene expression profiling indicated DES-induced stage-specific immune alterations: immune cell signatures were enriched at PND21 and PND90 but diminished at PND46. Correspondingly, DES increased macrophage populations at PND21 while reducing T-lymphocyte numbers at PND46 and PND90. DES exposure also dysregulated inflammatory cytokine/chemokine expression in adult glands, suggesting a persistent inflammatory environment. In conclusion, in utero exposure to an estrogenic compound can reprogram mammary development, inducing long-term changes in the extracellular matrix and immune landscape. These disruptions to stromal-immune homeostasis may impair normal mammary morphogenesis and increase susceptibility to breast pathologies later in life.

pharmacology and toxicology↗

bioRxiv2025

Gap junction communication regulates luminal-myoepithelial crosstalk and cell differentiation in a bi-layered human mammary epithelial cell model

Interactions between luminal and myoepithelial cells are essential for proper mammary gland development and function. However, only a few in vitro models allow the study of these interactions and their modulation by extrinsic factors. We developed a layered co-culture system (LCS) that mimics the bilayered architecture of the human breast epithelium, enabling direct contact and bidirectional crosstalk between luminal (MCF-12A) and myoepithelial (MYO1089) cells. We confirmed the formation of adherens and functional gap junctions across the layers. Transcriptomic analysis revealed that co-culture altered gene expression in pathways related to extracellular matrix remodeling, mRNA processing, response to external stimuli, hormonal signaling, receptor activity, and cell cycle regulation. In the LCS, MCF-12A cells exhibited a more luminal-like phenotype, with increased keratin-18 and decreased keratin-14, -smooth muscle actin (-SMA), and caldesmon-1 expression compared to 2D monoculture. Conversely, MYO1089 cells showed enhanced expression of myoepithelial markers, including -SMA, keratin-14, and caldesmon-1. Inhibition of gap junction communication by carbenoxolone disrupted these lineage-specific differentiation patterns. These findings highlight the importance of direct communication in regulating epithelial identity and underscore the LCS as a physiologically relevant model for studying mammary gland biology and external influences that can impact the epithelial differentiation. HighlightsA novel bilayered human co-culture system mimics the luminal and myoepithelial architecture of the mammary epithelium Direct luminal-myoepithelial contact enables formation of functional adherens and gap junctions Direct communication via gap junctions is essential for lineage-specific epithelial differentiation Co-culture induces transcriptional shifts related to proliferation, ECM regulation, and hormone response

cell biology↗

bioRxiv2020

DNA break clustering inside repair domains predicts cell death and mutation frequency in human fibroblasts and in Chinese hamster cells for a 10^3x range of linear energy transfers

Cosmic radiation, composed of high charged and energy (HZE) particles, causes cell death and mutations that can subsequently lead to cancers. Radiation-mediated mutations are induced by inter- and intra-chromosomal rearrangements (translocations, deletions, inversions) that are triggered by misrepaired DNA breaks, especially double-strand breaks (DSBs). In this work, we introduce a new model to predict radiation-mediated induction of cell death and mutation in two different cell lines across a large range of linear energy transfer (LET) values, based on the assumption that DSBs cluster into repair domains, as previously suggested by our group. Specifically, we propose that the probabilities of cell survival and cell mutation can be determined from the number of DSBs and the number of pairwise DSB interactions forming radiation-induced foci. We computed the distribution and locations of DSBs with the new simulation code RITCARD (relativistic ion tracks, chromosome aberrations, repair, and damage) and combined them with experimental data from HF19 human fibroblasts and V79 Chinese hamster cells to derive the parameters of our model and expand its predictions to the relative biological effectiveness (RBE) for cell survival and mutation in both cell lines in response to 9 different irradiation particles and energies ranging from 10 to 1,600 MeV/n. Our model generates the correct bell shape of LET dependence for RBE, as well as similar RBE values as experimental data, notably including data that were not used to set the model parameters. Interestingly, our results also suggest that cell orientation (parallel or perpendicular) with respect to the HZE beam can modulate the RBE for both cell death and mutation frequency. Cell orientation effects, if confirmed experimentally, would be another strong piece of evidence for the existence of DNA repair domains and their critical role in interpreting cellular sensitivity to cosmic radiation and hadron therapy. AUTHOR SUMMARYOne of the main hazards of human spaceflight beyond low Earth orbit is space radiation exposure. Galactic cosmic rays (GCRs), in particular their high-charge and high-energy particle component, induce a unique spatial distribution of DNA double strand breaks in the nucleus along their traversal in the cell [1], which result in significantly higher cancer risk than X-rays [2]. To mitigate this hazard, there is a significant need to better understand and predict the effects of cosmic radiation exposure at the cellular level. We have computationally predicted two biological endpoints - cell survival and probability of mutations, critical for cancer induction mechanisms - for the full spectrum of cosmic radiation types and energies, by modeling the distribution of DNA damage locations within the cell nucleus. From experimental results of cell survival and mutation probability in two standard cell lines, we were able to derive the parameters of the model for multiple radiation qualities, both biological endpoints, and two irradiation orientations. The model was validated against biological data and showed high predictive capability on data not used for tuning the model. Overall, this work opens new perspectives to predict multiple responses to cosmic radiation, even with limited experimental data available.

cell biology↗

bioRxiv2018

Luminal MCF-12A and myoepithelial-like Hs 578Bst cells form bilayered acini similar to human breast

2.3.1The mammary gland is a complex organ, structured in a ramified epithelium supported by the stroma. The epitheliums functional unit is the bilayered acinus, made of a layer of luminal cells surrounded by a layer of basal cells mainly composed of myoepithelial cells. The aim of this study was to develop a reproducible and manipulable three-dimensional co-culture model of the bilayered acinus in vitro to study the interactions between the two layers. Two different combinations of cell lines were co-cultured in Matrigel: SCp2 and SCg6 mice cells, or MCF-12A and Hs 578Bst human cell lines. Cell ratios and Matrigel concentration were optimized. The resulting acini were analysed by confocal microscopy using epithelial (E-cadherin) and myoepithelial (-smooth muscle actin) markers. SCp2 and SCg6 cells formed distinct three-dimensional structures, whereas MCF-12A and Hs 578Bst cells formed some bilayered acini. This in vitro bilayered acini model will allow us to understand the role of interactions between luminal and myoepithelial cells in the normal breast development.

cell biology↗