Chronically elevated androgen and/or consumption of a Western-style diet impairs oocyte quality and granulosa cell function in the nonhuman primate periovulatory follicle.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA528112 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8754630.fastq.gz | Fastqsanger.gz | |||
| SRR8754640.fastq.gz | Fastqsanger.gz | |||
| SRR8754631.fastq.gz | Fastqsanger.gz | |||
| SRR8754641.fastq.gz | Fastqsanger.gz | |||
| SRR8754632.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: To investigate the impact of chronically-elevated androgens in presence and absence of an obesogenic diet on oocyte quality in the naturally-selected primate periovulatory follicle. Methods: Rhesus macaques were treated using a 2-by-2 factorial design (n=10/treatment) near onset of menarche with implants containing either cholesterol (C) or testosterone (T; 4-5 fold increase above C) and a standard or “Western-style” diet alone (WSD), or in combination (T+WSD). Following ~3.5 years of treatment, females underwent controlled ovulation (COv; n=7-10/treatment) cycles, and contents of the naturally-selected periovulatory follicle were aspirated. Follicular fluid (FF) was analyzed for cytokines, chemokines, growth factors, and steroids. RNA was extracted from luteinizing granulosa cells (LGCs) and assessed by RNA-seq. Results: Only healthy, metaphase (M) I/II-stage oocytes (100%) were retrieved in the C group, whereas degenerated oocytes were prevalent in other groups (33-43%; overall effect of WSD and T, p=0.1). Levels of two chemokines and one growth factor were reduced (p<0.04) in FF of follicles with a MI/MII oocyte in WSD+T (CCL11) or T and WSD+T groups (CCL2 and FGF2) compared to C and/or WSD. Intrafollicular cortisol was elevated in T compared to C follicles (p<0.02). Changes in expression pattern of 640+ gene products were detected in LGC samples from follicles with degenerated oocytes versus MI/MII-stage oocytes. Pathway analysis on RNAs altered by T and/or WSD found enrichment of genes mapping to steroidogenic and immune cell pathways. Conclusions: Female primates experiencing hyperandrogenemia and/or consuming a WSD exhibit an altered intrafollicular microenvironment and reduced oocyte quality/competency, despite displaying menstrual cyclicity.
2019-09-05 | GSE128569 | GEO
Project description:PURPOSE:To investigate the impact of chronically elevated androgens in the presence and absence of an obesogenic diet on oocyte quality in the naturally selected primate periovulatory follicle. METHODS:Rhesus macaques were treated using a 2-by-2 factorial design (n?=?10/treatment) near the onset of menarche with implants containing either cholesterol (C) or testosterone (T, 4-5-fold increase above C) and a standard or "Western-style" diet alone (WSD) or in combination (T+WSD). Following ~?3.5 years of treatment, females underwent controlled ovulation (COv, n?=?7-10/treatment) cycles, and contents of the naturally selected periovulatory follicle were aspirated. Follicular fluid (FF) was analyzed for cytokines, chemokines, growth factors, and steroids. RNA was extracted from luteinizing granulosa cells (LGCs) and assessed by RNA-seq. RESULTS:Only healthy, metaphase (M) I/II-stage oocytes (100%) were retrieved in the C group, whereas several degenerated oocytes were recovered in other groups (33-43% of T, WSD, and T+WSD samples). Levels of two chemokines and one growth factor were reduced (p?<?0.04) in FF of follicles with a MI/MII oocyte in WSD+T (CCL11) or T and WSD+T groups (CCL2 and FGF2) compared to C and/or WSD. Intrafollicular cortisol was elevated in T compared to C follicles (p?<?0.02). Changes in the expression pattern of 640+ gene products were detected in LGC samples from follicles with degenerated versus MI/MII-stage oocytes. Pathway analysis on RNAs altered by T and/or WSD found enrichment of genes mapping to steroidogenic and immune cell pathways. CONCLUSIONS:Female primates experiencing hyperandrogenemia and/or consuming a WSD exhibit an altered intrafollicular microenvironment and reduced oocyte quality/competency, despite displaying menstrual cyclicity.
| S-EPMC6657409 | biostudies-literature
Project description:To investigate the effect of wetern-style diet on Paneth cells, we performed bulk RNAseq on sorted Paneth cells from mice fed for 3 months with western-style diet (NWD1) and control diet (AIN76A)
2024-03-27 | GSE221818 | GEO
Project description:Consumption of a Western-style diet impairs the ovarian follicular microenvironment and preimplantation development without changes in insulin resistance and body fat percentage in non-human primates.
2021-02-15 | GSE162817 | GEO
Project description:The investigators are involved in a research program to understand how different diets may affect the risk of colorectal polyps and cancer. To that end, the investigators are conducting a study of a western style diet versus a "prudent style" diet in which volunteer subjects are provided a different diet for 2 separate 4 week periods at the Rockefeller University Hospital. During one of these 4 week inpatient periods they receive a Western style diet and during the other 4 week inpatient period they receive a "Prudent style" diet. The investigators will determine changes within the colon as a result of the two different diets. A more detailed description of the study is provided below.
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Project description:To determine the effect of consumption of a quercetin-rich diet on obesity and dysregulated hepatic gene expression, C56BL/6J mice were fed for 20 weeks on control or a Western diet high in fat, cholesterol and sucrose, both with or without 0.05% quercetin. Chronic dietary intake of quercetin reduced body weight gain and visceral and liver fat accumulation, and improved hyperglyceamia, hyperinsulinaemia, dyslipidaemia in mice fed a Western-style diet. Feeding a Western-style diet altered expression of genes related to inflammatory responses, lipid metabolism and oxidative phosphorylation in C57BL/6J mice after 20 weeks. The results from exhaustive gene expression analysis showed that quercetin minimally influenced hepatic gene expression in mice fed the Western diet. The gene screening results (GSEA) were consistent with the notion that it did improve mitochondrial function to some extent. Quantitative RT-PCR analysis indicated that quercetin did influence important regulators of fat accumulation and metabolic disorders. Our results suggest that quercetin reduces fat accumulation presumably through decreasing oxidative stress and increasing PPARα expression, and the following improvement of gene expression related to steatosis in the liver.
2012-05-30 | GSE38141 | GEO
Project description:We reported that consumption of a western-style diet (WSD) with and without hyperandrogenemia perturbed placental perfusion and altered levels of glucose transporter proteins in rhesus macaques. Based on that result, we hypothesized that placental glucose uptake would be dysregulated in this model. In this study, female rhesus macaques were assigned at puberty to one of four groups: subcutaneous cholesterol implants + standard chow diet (controls, C); testosterone implants + chow (T); cholesterol implants + a high-fat, WSD; and T+WSD. After ~6 years of treatment, animals were mated, and pregnancies were delivered by cesarean section at gestational day (G) 130 (the term is G168). Placental villous explants were immediately prepared for radiolabeled glucose assay. Linear glucose uptake was observed between 0 and 30 s. At 20 s, glucose uptake in placental villous explants did not differ across the four treatment groups with values as follows: C: 25.5 ± 6.33, T: 22.9 ± 0.404, WSD: 26.9.0 ± 3.71, and T+WSD: 33.0 ± 3.12 (mean ± SD expressed in pmol/mg). Unlike our prior experiment, glucose transporter expression was reduced in WSD placentas, and our in vitro functional assay did not demonstrate a difference in glucose uptake across the transporting epithelium of the placenta. Notably, maternal blood glucose levels were significantly elevated in animals chronically fed a WSD. This disparity may indicate differences in glucose utilization and metabolism by the placenta itself, as glucose transporter expression and circulating fetal glucose concentrations were comparable across all four groups in this pregnancy cohort.
| S-EPMC8349840 | biostudies-literature
Project description:Some previous experimental studies have shown that early in life intake of high-fat or Western-style diets did alter the development of mammary cancer in adulthood female rats. Thus, the present study investigated the distinct gene expression patterns of chemically induced mammary tumors derived from female offspring whose dams intake control diet (CD) or Western-style diet (WD). During gestational days (GD) 12-21 and post-natal days (PND) 1-21, pregnant Sprague-Dawley (SD) rats were fed a CD diet or WD (high-fat and low-fiber and oligoelements) diet. On postnatal day (PND) 21, the female offspring received a single dose of carcinogen N-Methyl-N-Nitrosourea (MNU, 50 mg/kg) and CD diet for 12 weeks. Latency, incidence and tumor burden were registered. Mammary tumors samples were collected and histopathology and gene expression analysis were performed.
2018-10-12 | GSE96520 | GEO
Project description:Pediatric nonalcoholic fatty liver disease (NAFLD) has distinct and variable pathology that affects up to 10% of children, yet causation remains unclear. We have shown that maternal Western- style diet (mWSD) compared with chow diet (mCD) consumption in nonhuman primates (NHP) produces hepatic injury and steatosis in fetal offspring. Here, we define the role of mWSD and postweaning WSD (pwWSD) exposures on potential molecular mechanisms linked to NAFLD development in a cohort of 3-year-old (3YO) juvenile NHP offspring exposed to mCD or mWSD followed by CD or WSD after weaning. We used histologic, transcriptomic, and metabolomic analyses to identify hepatic pathways regulating NAFLD. Offspring exposed to mWSD showed increased hepatic periportal collagen deposition but unchanged hepatic triglyceride levels and body weight. mWSD was associated with a down-regulation of gene expression pathways underlying HNF4 activity, antioxidant signaling, mitochondrial biogenesis, and PPAR signaling. In offspring exposed to both mWSD and pwWSD, liver RNA profiles showed up-regulation of pathways promoting fibrosis and ER stress. pwWSD increased acylcarnitines and decreased anti- inflammatory fatty acids, which was more pronounced when coupled with mWSD exposure. Further, mWSD shifted liver metabolites towards decreased purine catabolism in favor of synthesis, suggesting a mitochondrial DNA repair response.
2022-12-05 | GSE220102 | GEO
Project description:We have recently developed a nonhuman primate (NHP) model to address the effects of hyperandrogenemia (modestly elevated testosterone; T), a high-fat, obesogenic Western-style diet (WSD), or combined T+WSD. To address the molecular mechanisms underlying adipocyte dysfunction, visceral adipose tissue biopsies were analyzed for whole-genome gene expression and DNA methylation, using RNA-seq and reduced-representation bisulfite sequencing (RRBS), respectively. We show that the combination of T + WSD induces a significantly stronger transcriptional response than T or WSD alone, including regulation of genes whose expression is altered in adipose tissue of PCOS women. Gene expression patterns indicate alterations in cAMP, LXR/RXR, HIPPO, Wnt signaling and eicosanoid and retinol biosynthesis pathways. Analysis of DNA methylation shows that genes from the cAMP signaling pathway are also differentially methylated in T +WSD, which also globally resulted in a greater number of differentially methylated regions (DMRs) than T or WSD alone. Collectively, our results show that hyperandrogenemia and WSD exhibit synergistic effects on the visceral adipose tissue transcriptome and methylome, resulting in activation of biological processes that may contribute to the adipose tissue dysfunction characteristic of PCOS.
2019-01-07 | GSE124708 | GEO