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Project description:Gene expression profiling of blood cells in patients with major depressive disorder (MDD) has been used to identify potential biomarkers and to address the pathophysiology of MDD. However, whether alteration in gene expression in blood cells are reflected in the brain of the same individual is unclear. Here, we used an animal model of depression to investigate intra-subject correlation of gene expression patterns between the whole blood (WB) and the medial prefrontal cortex (mPFC). Ovariectomized mice exposed to the chronic ultra-mild stress were used as an animal model of depression. The major findings of the current genome-wide microarray analysis are that 1) the expression levels of 467 genes that were expressed in both tissues correlated positively between the two tissues, 2) alterations in the expression of 4,215 genes in the WB of OVX-operated mice compared to the sham-operated mice were concordant with alterations in the corresponding mPFC, 3) the biological terms over-represented in the 4,215 OVX-affected genes were associated with ribosomal function, and 4) the 6 genes that are potentially relevant to depression-like behavior were observed to be differentially expressed in the WB of the model mice. The current findings suggest that alterations in the expression of a subset of genes are significantly correlated between the WB and the mPFC with in the same individual in an experimental model of depression. Female mice were subjected to chronic ultra-mild stress, a bilateral ovariectomy, or both. Sham-operated mice without stress were used as the control. Medial prefrontal cortex and whole blood were obtained from the same individual (n = 6 in each group), and analyzed using an Agilent SurePrint G3 Mouse GE 8×60K Microarray (Design ID: 028005)
2015-08-21 | E-GEOD-72262 | biostudies-arrayexpress
Project description:Purpose: Using RNA-sequencing technology to screen the effect of moderate-intensity treadmill exercise on the key genes that affect bone mass in the peripheral blood mononuclear cells (PBMCs) of ovariectomized (OVX) rats. Methods: Three-month-old female Sprague–Dawley rats of Specific Pathogen Free (SPF) grade were randomly divided into the sham operation (SHAM) group, OVX group, and OVX combined exercise (OVX+EX) group. The OVX+EX group performed moderate-intensity treadmill exercise for 17 weeks. Upon completion of these exercises, the body composition and bone mineral density (BMD) were measured using dual-energy X-ray absorptiometry, and the bone microstructure of the femur was observed using micro-computed tomography scanning. PBMCs were collected from the abdominal aorta, and the differential genes were analyzed by transcriptome sequencing. The Metascape software was used for gene ontology and pathway enrichment analysis to further screen key genes. Results: 1. In the OVX group, the body weight and body fat content were significantly higher than in the SHAM group and the body muscle content and BMD were significantly lower. 2. The trabecular bone parameters in the OVX group were significantly lower than in the SHAM group, and they were significantly higher in the OVX+EX group than in the OVX group. When compared with the SHAM group, the microstructure of the distal femur trabecular in the OVX group was severely damaged, the trabecular bones were sparse, and there was a large gap between the trabecular bones. The number and continuity of the trabecular bones were higher in OVX+EX group than in the OVX group. 3. A Venn diagram showed that there were 58 common differential genes, with a fold change ≥2 and p value <0.05. and the differential genes were mainly enriched in the PI3K-Akt signaling pathway. Five key genes were screened including CCL2, Nos3, Tgfb3, ITGb4, and LpL. Conclusion: Moderate-intensity treadmill exercise may improve the body composition and bone mass of the OVX group by upregulating CCL2 and other genes of the PBMC. The results also showed that the PBMCs in the peripheral blood can be a useful tool for monitoring the effect of exercise on bone health in postmenopausal osteoporosis.
2021-11-17 | GSE184493 | GEO
Project description:There is an increasing clinical evidence that obesity exerts deleterious effects on the skeleton. While obesity coexists with estrogen deficiency in postmenopausal women, their combined effects on the skeleton are poorly studied. Thus, we investigated the impact of high-fat diet (HFD) on bone and metabolism of ovariectomized (OVX) female mice (C57BL/6J). OVX or sham operated mice were fed either HFD (60%fat) or normal diet (ND) (10%fat) for 12 weeks. HFD-OVX group exhibited pronounced increase in body weight (~86% in HFD and ~122% in HFD-OVX, p<0.0005) and impaired glucose tolerance. Bone microCT-scanning revealed a pronounced decrease in trabecular bone volume/total volume (BV/TV) in HFD-OVX (15.6±0.48% in HFD and 37.5±0.235% in HFD-OVX, p<0.005) and expansion of bone marrow adipose tissue (BMAT) (+60.7±9.9% in HFD vs +79.5±5.86% in HFD-OVX, p<0.005). Mechanistically, HFD-OVX treatment led to upregulation of genes markers of senescence, bone resorption, adipogenesis and inflammation and downregulation of gene markers of bone formation and bone development. Similarly, HFD- OVX treatment resulted in significant changes in bone tissue levels of Purine/Pyrimidine and Glutamate metabolisms, known to play a regulatory role in bone metabolism. Obesity and estrogen deficiency exert combined deleterious effects on bone resulting in accelerated cellular senescence, expansion of BMAT and impaired bone formation leading to decreased bone mass. Our results suggest that obesity may increase bone fragility in post-menopausal women.
2022-12-05 | GSE194075 | GEO
Project description:For premenopausal women with primary ER+ breast cancer, oophorectomy (OvX) is an evidence-based cost-effective option and is standard treatment in many countries. However, there is virtually no data describing the effects of OvX on breast tumour biology. We therefore characterized the endocrine and genome-wide transcriptional impact of OvX in 56 premenopausal women with ER+ breast cancer for two weeks prior to mastectomy. Plasma estradiol concentrations decreased from 421±305 to 24.1±24.5 pmol/l (mean±sd) 24 hours after OvX and to 8.8±7.3pmol/l two weeks later at mastectomy. Ki67 decreased in 33/36 (91.7%) tumours. The expression of 655 genes changed significantly (FDR<1%) with an absolute mean fold-change (FC) ≥1.25 (257 up, 398 down). Archetypal oestrogen-regulated genes, proliferation-associated genes and putative progesterone-regulated genes were strongly down-regulated. The gene expression changes did not differ according to HER2 status and correlated strongly with those after aromatase inhibitor (AI) treatment in 81 postmenopausal women. However, after OvX the mean FC was significantly higher compared to AI. In conclusion, changes in tumoural gene expression after OvX were largely similar but of a greater magnitude to those observed after AI in postmenopausal patients but OvX appeared to have a greater effect on progesterone-regulated genes than AI.
2018-02-14 | GSE97221 | GEO
Project description:BMSC-derived exosomes from ovariectomized rats (OVX-Exo) and sham-operated rats (Sham-Exo) were co-cultured with bone marrow-derived macrophages to study their effects on osteoclast differentiation. Next-generation sequencing was utilized to identify the differentially expressed miRNAs (DE-miRNAs) in OVX-Exo and Sham-Exo, while target genes were analyzed using bioinformatics. The regulatory effects of miR-27a-3p and miR-196b-5p on osteogenic differentiation of BMSCs and osteoclast differentiation were verified by gain-of-function and loss-of-function analyses.Osteoclast differentiation was significantly enhanced in the OVX-Exo treatment group compared to the Sham-Exo group. Twenty DE-miRNAs were identified in OVX-Exo and Sham-Exo, among which miR-27a-3p and miR-196b-5p promoted the expressions of osteogenic genes in BMSCs. In contrast, knockdown of miR-27a-3p and miR-196b-5p increased the expressions of osteoclastic genes in osteoclasts. These 20 DE-miRNAs were found to target 11435 mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these target genes were involved in several biological processes and osteoporosis-related signaling pathways.
2022-07-07 | GSE197085 | GEO
Project description:The peri- and postmenopausal periods in women are associated with decreases in circulating estrogen levels, marked acceleration of age-related bone loss and increased risk of fracture. However, despite the clinical importance of postmenopausal bone loss, our molecular understanding of this process is incomplete. Here, we used co-expression network analysis to gain novel insight into the molecular mechanisms mediating bone loss in ovariectomized (OVX) mice, a model of human menopause. Expression profiles from intact and OVX mice from a panel of inbred strains were used to generate a co-expression network consisting of 29 modules. Genes in network module 25 were decreased by OVX in all strains. Module 25 was enriched for genes involved in the response to oxidative stress, a process known to be an upstream causal factor for OVX-induced bone loss. It was also found that module 25 homologs were co-expressed in human bone marrow and were enriched for genes with evidence of genetic association with bone mineral density (BMD) in women. Alpha synuclein (Snca) was the most highly connected “hub” genes in module 25 and its in vivo knockout resulted in a 40% reduction in OVX-induced bone loss. Furthermore, protection was associated with the targeted alteration of genes in specific network modules, including module 10. Our results identify a gene module associated with OVX-induced bone loss and demonstrate that Snca regulates ovariectomy-induced bone loss by controlling bone network dynamics.
2016-12-01 | GSE68303 | GEO
Project description:The peri- and postmenopausal periods in women are associated with decreases in circulating estrogen levels, marked acceleration of age-related bone loss and increased risk of fracture. However, despite the clinical importance of postmenopausal bone loss, our molecular understanding of this process is incomplete. Here, we used co-expression network analysis to gain novel insight into the molecular mechanisms mediating bone loss in ovariectomized (OVX) mice, a model of human menopause. Expression profiles from intact and OVX mice from a panel of inbred strains were used to generate a co-expression network consisting of 29 modules. Genes in network module 25 were decreased by OVX in all strains. Module 25 was enriched for genes involved in the response to oxidative stress, a process known to be an upstream causal factor for OVX-induced bone loss. It was also found that module 25 homologs were co-expressed in human bone marrow and were enriched for genes with evidence of genetic association with bone mineral density (BMD) in women. Alpha synuclein (Snca) was the most highly connected “hub” genes in module 25 and its in vivo knockout resulted in a 40% reduction in OVX-induced bone loss. Furthermore, protection was associated with the targeted alteration of genes in specific network modules, including module 10. Our results identify a gene module associated with OVX-induced bone loss and demonstrate that Snca regulates ovariectomy-induced bone loss by controlling bone network dynamics.
2016-12-01 | GSE68302 | GEO
Project description:Despite an abundance of evidence to the contrary from animal studies, large clinical trials on humans have shown that estrogen administered to post-menopausal women increases the risk of cardiovascular disease. However, timing may be everything, as estrogen is often administered immediately after ovariectomy (ovx) in animal studies, while estrogen administration in human studies occurred many years post-menopause. This study investigates the discrepancy by administering 17ß-estradiol (E2) in a slow-release capsule to Norway Brown rats both immediately following ovx and 9 weeks post-ovx (Late), and studying differences in gene expression between these 2 groups as compared to age-matched ovx and sham operated animals. Two different types of microarray were used to analyze the left ventricles from these groups: an Affymetrix array (2 samples/group, each sample contained total RNAs pooled from 3 rats) and an Inflammatory Cytokines and Receptors PCR array (N=4 /group). Key genes were analyzed by western blotting. Ovx without replacement led to an increase in caspase 3, caspase 9, calpain 2, MMP9, and TNFα. Caspase 6, STAT3, and CD11b increased in the Late group, while TIMP2, MMP14, and collagen I α1 were decreased. MADD and fibronectin were increased in both Ovx and Late. TNFα protein levels increased with Late replacement. Many of these changes were prevented by early E2 replacement. These findings suggest that increased TNFα may be involved in some of the deleterious effects of delayed E2 administration seen in human studies.
2011-07-23 | GSE30851 | GEO
Project description:Effective antiretroviral therapy (ART) has significantly reduced mortality of people living with HIV (PLWH). Increased survival and aging of PLWH is associated with increased incidence of at-risk alcohol use and of metabolic comorbidities; and in women, menopause may be an additional factor contributing to metabolic dysregulation, particularly in adipose tissue. We examined the differential effects of chronic binge alcohol (CBA) administration and ovariectomy (OVX) on the omental adipose tissue (OmAT) proteome of simian immunodeficiency virus (SIV) infected macaques. Quantitative discovery-based proteomics identified 1429 differentially expressed proteins. Ingenuity Pathway Analysis calculated z-scores, or activation predictions for a disease or functional pathway. Results revealed functional pathways associated with protein changes centered around the “OmAT metaboproteome profile”. CBA did not affect functional pathways of metabolic disease; but dysregulated proteins involved in AMPK signaling and lipid metabolism. Based on IPA’s calculated z-score, OVX-mediated proteome changes promote pathways associated with glucose and lipid associated metabolic disease. Additionally, OVX was predicted to promote apoptosis, necrosis and reactive oxygen species (ROS) pathways, while CBA was predicted to inhibit these OVX-associated changes. These results provide evidence for the role of ovarian hormone loss in mediating OmAT metaboproteome dysregulation in HIV/SIV and suggest that CBA modifies OVX-associated changes. In the context of OVX, CBA administraton produced larger metabolic and cellular effects; which we speculate may reflect a protective role of estrogen against CBA-mediated adipose tissue injury in female SIV-infected macaques.
2022-08-12 | PXD023076 | Pride
Project description:Among female Long-Evans rats, mating enhances neurosteroid formation in the midbrain ventral tegmental area (independent of peripheral steroid-secreting glands, the ovaries and adrenals). The sources/targets for these actions are not well-understood. In Experiment 1, proestrous rats engaged in a mating paradigm, or did not, and had midbrains assessed via Affymetrix rat genome microarrays. In Experiment 2, the influence of gonadal and adrenal glands on the expression of these genes was assessed in rats that were proestrous, ovariectomized (OVX), or OVX and adrenalectomized (ADX). Microarrays revealed 53 target genes that were significantly up-regulated (> 2.0-fold change) in response to mating. Mating significantly enhanced midbrain mRNA expression of genes involved in hormonal and trophic actions: Gh1, S100g, and Klk1b3 in proestrous, but not OVX and/or ADX, rats; Fshb in all but OVX/ADX rats; and Lhb and Tshb in all rats. Thus, mating enhances midbrain gene expression, independent and dependent of, peripheral glands.
2019-02-28 | GSE127272 | GEO