Project description:Chronic dietary aspartame may impair rodent insulin tolerance and may affect behavior. Previous studies have shown the aspartame effects may be modulated by developmental NMDA receptor antagonism. Present study was designed to assess effects of aspartame and NMDAR antagonism on components of the HPA axis. We used microarray analysis to examine changes in adult rodent adrenal gene expression following chronic aspartame exposure and/or developmental NMDA receptor antagonism.
Project description:Two strains of rodent C57Bl/6J and KK/HIJ were compared to find the most suitable rodent model of obesity and type 2 diabetes. KK/HIJ become larger and glucose intolerant on standard chow but are not as well characterized as the C67Bl/6J model which has a more defined behavioral phenotype. The present study is to asses and determie the most suitable mouse model for our research. We used microarray analysis to examine differences in gene expression in C57Bl/6J and KK/HIJ , male and female adult rodent mice
Project description:This study employs spatial transcriptomics to map the molecular landscape of the mouse adrenal gland, focusing on distinct cortical zones (zona glomerulosa, zona fasciculata, X-zone) and the adrenal medulla, as well as adjacent adipose tissue. Using Visium CytAssist technology, we analyzed adrenal sections from male CD-1® IGS mice, identifying seven distinct cell clusters, including brown and white adipose tissues.
Project description:Transcription factor GATA6 is expressed in the fetal and adult adrenal cortex and has been implicated in steroidogenesis. To characterize the role of GATA6 in adrenocortical development and function, we generated mice in which Gata6 was conditionally deleted using Cre-LoxP recombination with Sf1-cre. The adrenal glands of adult Gata6 conditional knockout (cKO) mice were small and had a thin cortex with thickened capsule. Cytomegalic changes were evident in the adrenal glands of fetal and adult cKO mice, and chromaffin cells were ectopically located at the periphery of the glands. The secretion of corticosterone in response to exogenous ACTH was blunted in cKO mice. Cells expressing gonadal-like markers, including Gata4, Amhr2, and Tcf21, accumulated in the adrenal capsule and subcapsule of cKO mice, suggesting aberrant adrenocortical progenitor/stem cell differentiation. Gonadectomy triggered the overexpression of sex steroidogenic differentiation markers, such as Lhcgr and Cyp17, in the adrenal glands of male and female cKO mice. Nulliparous female and orchiectomized male cKO mice lacked an adrenal X-zone. Microarray hybridization identified Pik3c2g as a novel X-zone marker that is downregulated in the adrenal glands of nulliparous female Gata6 cKO mice. Our findings offer genetic proof of the longstanding hypothesis that GATA6 regulates the differentiation of steroidogenic progenitors into corticoid-producing cells. 3 replicates from both conditional knockout of Gata6 in the adrenal gland and control adrenal glands from non-knockout mice were compared
Project description:The adrenal gland is a fundamental endocrine organ exhibiting constant renewal. Despite extensive work in rodents, human-specific aspects of hormone-producing cell populations, stem cells, and self-renewal mechanisms are not fully understood. To fill this knowledge gap and address species-specific features, we generated high density single-cell and spatial transcriptomics atlases of adult human and mouse adrenal glands using Visium, VisiumHD and Stereo-seq, covering a spectrum of sexes and ages. Our comparisons between human and murine adrenal gland revealed significant evolutionary divergence despite homology in function of specific regions, which questiones the applicability of mouse models in studies of human adrenal disorders. Self-renewal mechanisms in adrenocortical populations that were previously discovered in mice also revealed human-specific features or were confronted by human-specific transitions not evident in rodents. The latter included specific perivascular mesenchymal progenitors, and dispersed SF1+/EZH2+ progenitor cells, which implies that human adrenocortical cells may be renewed in a localized manner in addition to the centripetal model. We also engaged in cross-comparison of our adult human adrenals with fetal stages to reveal developmental strategies still operating as a part of self-renewal in adults. Unexpectedly, human SF1+/EZH2+ progenitors turned out to be operating during adrenocortical development and later during adult stages, albeit in different degrees. At last, we revealed sex-specific differences in human cholesterol metabolism and other features reflecting human and mouse sexual dimorphism in adrenal glands. Overall, our new comparative mouse-human atlases shall provide an additional resource for further molecular interrogations of adrenal gland biology and pathology.
Project description:The objective of the experiment is to determine the genes differentially expressed in the adrenal gland of adult (12-week) BPH and BPL mice. Adrenal glands from adult (12-week) hypertensive BPH mice (n=3) and adult (12-week) hypotensive BPL mice (n=3).
Project description:Transcription factor GATA6 is expressed in the fetal and adult adrenal cortex and has been implicated in steroidogenesis. To characterize the role of GATA6 in adrenocortical development and function, we generated mice in which Gata6 was conditionally deleted using Cre-LoxP recombination with Sf1-cre. The adrenal glands of adult Gata6 conditional knockout (cKO) mice were small and had a thin cortex with thickened capsule. Cytomegalic changes were evident in the adrenal glands of fetal and adult cKO mice, and chromaffin cells were ectopically located at the periphery of the glands. The secretion of corticosterone in response to exogenous ACTH was blunted in cKO mice. Cells expressing gonadal-like markers, including Gata4, Amhr2, and Tcf21, accumulated in the adrenal capsule and subcapsule of cKO mice, suggesting aberrant adrenocortical progenitor/stem cell differentiation. Gonadectomy triggered the overexpression of sex steroidogenic differentiation markers, such as Lhcgr and Cyp17, in the adrenal glands of male and female cKO mice. Nulliparous female and orchiectomized male cKO mice lacked an adrenal X-zone. Microarray hybridization identified Pik3c2g as a novel X-zone marker that is downregulated in the adrenal glands of nulliparous female Gata6 cKO mice. Our findings offer genetic proof of the longstanding hypothesis that GATA6 regulates the differentiation of steroidogenic progenitors into corticoid-producing cells.