Long-Term Hyperandrogenemia and/or Western-Style Diet Treatment Impairs Rhesus Macaque Preimplantation Embryo Development
Ontology highlight
ABSTRACT:
ORGANISM(S): Macaca mulatta
PROVIDER: GSE186969 | GEO | 2022/04/01
REPOSITORIES: GEO
Similar Datasets
Project description:Hyperandrogenemia and obesity are common in women with polycystic ovary syndrome, but it is currently unclear how each alone or in combination contribute to reproductive dysfunction and female infertility. To distinguish the individual and combined effects of hyperandrogenemia and an obesogenic diet on ovarian function, prepubertal female rhesus macaques received a standard control (C) diet, testosterone (T) implants, an obesogenic Western-style diet (WSD), or both (T + WSD). After 5 to 6 years of treatment, the females underwent metabolic assessments and controlled ovarian stimulations. Follicular fluid (FF) was collected for steroid and cytokine analysis and the oocytes fertilized in vitro. Although the T + WSD females exhibited higher insulin resistance compared to the controls, there were no significant differences in metabolic parameters between treatments. Significantly higher concentrations of CXCL-10 were detected in the FF from the T group, but no significant differences in intrafollicular steroid levels were observed. Immunostaining of cleavage-stage embryos revealed multiple nuclear abnormalities in the T, WSD, and T + WSD groups. Single-cell DNA sequencing showed that while C embryos contained primarily euploid blastomeres, most cells in the other treatment groups were aneuploid. Despite yielding a higher number of mature oocytes, T + WSD treatment resulted in significantly reduced blastocyst formation rates compared to the T group. RNA sequencing analysis of individual blastocysts showed differential expression of genes involved in critical implantation processes between the C group and other treatments. Collectively, we show that long-term WSD consumption reduces the capacity of fertilized oocytes to develop into blastocysts and that the addition of T further impacts gene expression and embryogenesis.
| S-EPMC8962721 | biostudies-literature
Project description:This study examined the small antral follicles (SAFs) in ovaries of young adult rhesus monkeys following consumption of a western-style diet (WSD), with or without chronically elevated androgen levels since before puberty. Cholesterol or testosterone (T; n=6/group) implants were placed subcutaneously beginning at 1 yr of age, with addition of a WSD (high fat/fructose) at 5.5 yrs. Ovaries from treated females and age-matched controls were collected at 7 yrs of age. Compared to controls, consumption of a WSD, with and without T treatment, increased the numbers of SAFs per ovary (P<0.001), due to the presence of more atretic follicles (P<0.01). Immunostaining for the cellular proliferation markers (pRb and pH3) was greater in granulosa cells of healthy SAFs (P<0.01), while staining for the cell cycle inhibitor (p21) was higher in atretic SAFs (P<0.01). Intense CYP17A1 staining was observed on the theca of SAFs from WSD+/- T groups, compared to controls. Microarray analyses of the transcriptome in SAFs isolated from a subgroup (n=3/grp) of WSD and WSD+T treated females and controls consuming a standard diet, identified mRNA levels for 1944 genes changed >2-fold (p<0.05) among the three groups. Pathway analyses identified several gene pathways altered by WSD and/or WSD+T associated with lipid, carbohydrate and lipid metabolism, plus ovarian processes. Alterations of several SAF mRNAs are similar to those observed in follicular cells from women with PCOS. These data indicate chronic exposure to a WSD in the presence and absence of chronically elevated T alters structure and function of SAFs within primate ovaries. Affymetrix Microarray analyses of the transcriptome in SAFs isolated from ovaries of WSD and WSD+T treated rhesus macaque females and controls consuming a standard diet. Presumptive healthy SAFs were chosen for transcriptome evaluation based on criteria similar to previous studies: the presence of a clear antrum lacking dark oocytes or granulosa cells. Isolated SAFs were pooled by female/ovary (3.7±0.3 SAFs/ovary, n=3 ovaries/group), cleaned of extraneous stroma using 30-gauge needles, ruptured, and entire cellular contents (follicle wall/granulosa cells and cumulous-oocyte complex) placed into lysis buffer for RNA isolation (Absolutely RNA Nanoprep Kit, Agilent Technologies, Inc. USA).
2015-12-21 | E-GEOD-69716 | biostudies-arrayexpress
Project description:This study examined the small antral follicles (SAFs) in ovaries of young adult rhesus monkeys following consumption of a western-style diet (WSD), with or without chronically elevated androgen levels since before puberty. Cholesterol or testosterone (T; n=6/group) implants were placed subcutaneously beginning at 1 yr of age, with addition of a WSD (high fat/fructose) at 5.5 yrs. Ovaries from treated females and age-matched controls were collected at 7 yrs of age. Compared to controls, consumption of a WSD, with and without T treatment, increased the numbers of SAFs per ovary (P<0.001), due to the presence of more atretic follicles (P<0.01). Immunostaining for the cellular proliferation markers (pRb and pH3) was greater in granulosa cells of healthy SAFs (P<0.01), while staining for the cell cycle inhibitor (p21) was higher in atretic SAFs (P<0.01). Intense CYP17A1 staining was observed on the theca of SAFs from WSD+/- T groups, compared to controls. Microarray analyses of the transcriptome in SAFs isolated from a subgroup (n=3/grp) of WSD and WSD+T treated females and controls consuming a standard diet, identified mRNA levels for 1944 genes changed >2-fold (p<0.05) among the three groups. Pathway analyses identified several gene pathways altered by WSD and/or WSD+T associated with lipid, carbohydrate and lipid metabolism, plus ovarian processes. Alterations of several SAF mRNAs are similar to those observed in follicular cells from women with PCOS. These data indicate chronic exposure to a WSD in the presence and absence of chronically elevated T alters structure and function of SAFs within primate ovaries.
2015-12-21 | GSE69716 | GEO
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:Maternal diet is associated with the development of metabolism-related and other non-communicable diseases in offspring. Underlying mechanisms, functional profiles, and molecular markers are only starting to be revealed. Here, we explored the physiological and molecular impact of maternal Western-style diet on the liver of male and female offspring. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) for six weeks before mating, as well as during gestation and lactation. Dams and offspring were sacrificed at postnatal day 14, and body, liver, and blood parameters were assessed. The impact of maternal WSD on the pups' liver gene expression was characterised by whole-transcriptome microarray analysis. Exclusively male offspring had significantly higher body weight upon maternal WSD. In offspring of both sexes of WSD dams, liver and blood parameters, as well as hepatic gene expression profiles were changed. In total, 686 and 604 genes were differentially expressed in liver (pM-bM-^IM-$0.01) of males and females, respectively. Only 10% of these significantly changed genes overlapped in both sexes. In males, in particular alterations of gene expression with respect to developmental functions and processes were observed, such as Wnt/beta-catenin signalling. In females, mainly genes important for lipid metabolism, including cholesterol synthesis, were changed. We conclude that maternal WSD affects physiological parameters and induces substantial changes in the molecular profile of the liver in two-week-old pups. Remarkably, the observed biological responses of the offspring reveal pronounced sex-specificity. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) as six weeks pre-treatment before mating, as well as during gestation and lactation. Offspring were sacrificed at postnatal week two, livers were removed and RNA samples were subjected to gene expression profiling.
2013-11-27 | E-GEOD-46359 | biostudies-arrayexpress
Project description:Long-Term Hyperandrogenemia and/or Western-Style Diet Treatment Impairs Rhesus Macaque Preimplantation Embryo Development
| PRJNA777041 | ENA
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
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 | GSE124707 | GEO
Project description:Maternal diet is associated with the development of metabolism-related and other non-communicable diseases in offspring. Underlying mechanisms, functional profiles, and molecular markers are only starting to be revealed. Here, we explored the physiological and molecular impact of maternal Western-style diet on the liver of male and female offspring. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) for six weeks before mating, as well as during gestation and lactation. Dams and offspring were sacrificed at postnatal day 14, and body, liver, and blood parameters were assessed. The impact of maternal WSD on the pups' liver gene expression was characterised by whole-transcriptome microarray analysis. Exclusively male offspring had significantly higher body weight upon maternal WSD. In offspring of both sexes of WSD dams, liver and blood parameters, as well as hepatic gene expression profiles were changed. In total, 686 and 604 genes were differentially expressed in liver (p≤0.01) of males and females, respectively. Only 10% of these significantly changed genes overlapped in both sexes. In males, in particular alterations of gene expression with respect to developmental functions and processes were observed, such as Wnt/beta-catenin signalling. In females, mainly genes important for lipid metabolism, including cholesterol synthesis, were changed. We conclude that maternal WSD affects physiological parameters and induces substantial changes in the molecular profile of the liver in two-week-old pups. Remarkably, the observed biological responses of the offspring reveal pronounced sex-specificity.
2013-11-27 | GSE46359 | GEO
Project description:Early mammalian embryonic transcriptomes are dynamic throughout the process of preimplantation development. Cataloging of primate transcriptomics during early development has been accomplished in humans, but global characterization of transcripts is lacking in the rhesus macaque: a key model for human reproductive processes. We report here the systematic classification of individual macaque transcriptomes using RNA-Seq technology from the germinal vesicle stage oocyte through the blastocyst stage embryo. Major differences in gene expression were found between sequential stages, with the 4- to 8-cell stages showing the highest level of differential gene expression. Analysis of putative transcription factor binding sites also revealed a striking increase in key regulatory factors in 8-cell embryos, indicating a strong likelihood of embryonic genome activation occurring at this stage. Furthermore, clustering analyses of gene co-expression throughout this period resulted in distinct groups of transcripts significantly associated to the different embryo stages assayed. The sequence data provided here along with characterizations of major regulatory transcript groups present a comprehensive atlas of polyadenylated transcripts that serves as a useful resource for comparative studies of preimplantation development in humans and other species.
| S-EPMC6279092 | biostudies-literature