Exposure to non-esterified fatty acids results in short- and long-term changes in the ovarian environment and granulosa cells
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ABSTRACT:
ORGANISM(S): Bos taurus
PROVIDER: GSE165476 | GEO | 2021/04/30
REPOSITORIES: GEO
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Project description:Exposure to non-esterified fatty acids results in short- and long-term changes in the ovarian environment and granulosa cells
| PRJNA694666 | ENA
Project description:BackgroundNon-esterified fatty acids (NEFAs) are one of the main lipid components of follicular fluid at concentrations that depend on circulating levels. Elevated levels of NEFAs impair oocyte quality, development potential, and may subsequently influence the metabolism and reproductive fitness of offspring. Granulosa cells (GCs) are the follicular cells that are closely communicating with the oocyte. However, the responses of GCs exposed to high levels of NEFAs when cocultured with cumulus-oocyte complexes (COCs), and how they attenuate the negative effects of NEFAs on oocytes, are unclear.ResultsTo better understand this protective effect, monolayers of porcine GCs were cocultured with COCs during in vitro maturation (IVM) in the presence of elevated levels of NEFAs. Genomic expression analysis was conducted to explore the responses of the GCs to the elevated levels of NEFAs. After limma algorithm analysis, 1,013 genes were differentially expressed between GCs cultured with and without elevated NEFAs. Among them, 438 genes were upregulated and 575 were downregulated. The differentially expressed genes were enriched in pathways related to metabolism, inflammation, and epithelial-mesenchymal transition.ConclusionsThe pathways and upstream regulators suggested that the cocultured GCs responded to the elevated NEFAs with (1) inhibition of the transition from granulosa to luteal cell, (2) interactions of metabolism change, anti-inflammation, mitochondrial function, and cell transition, (3) intercommunication with cocultured COCs of anti-inflammatory factors.
| S-EPMC8554973 | biostudies-literature
Project description:Metabolic stress associated with negative energy balance in high producing dairy cattle and obesity in women is a risk factor for decreased fertility. Non-esterified fatty acids (NEFA) are involved in this pathogenesis as they jeopardize oocyte and embryo development. Growing evidence indicates that maternal metabolic disorders can disturb epigenetic programming, and more specifically DNA methylation, in the offspring. Final oocyte maturation and early embryo development coincide with specific methylation changes and both time periods are sensitive to adverse environments. Therefore, we investigated whether elevated NEFA concentrations affect the establishment and maintenance of DNA methylation patterns in oocytes and embryos and subsequently alter transcriptomic profiles and developmental competence of the resultant blastocysts. To do this, bovine oocytes and embryos were exposed to different NEFA concentrations in two separate experiments. In the first experiment, oocytes were matured in vitro for 24 hours in medium containing: 1) physiological (âBASALâ) concentrations of oleic (OA), palmitic (PA) and stearic (SA) or 2) elevated (pathophysiological or âHIGH COMBIâ) concentrations of OA, PA and SA. In the second experiment, zygotes were cultivated in vitro for 6.5 days under BASAL or HIGH COMBI conditions. The developmental competence was evaluated by assessing cleavage and blastocyst rate. Overall gene expression and DNA methylation of resultant blastocysts were analyzed using microarray techniques. Data regarding DNA methylation were re-evaluated by pyrosequencing. HIGH COMBI-exposed oocytes and embryos displayed a lower competence to develop into blastocysts compared to their BASAL-exposed counterparts (19.3 % compared to 23.2 % and 18.2 % compared to 25.3 %, respectively) (P < 0.05). HIGH COMBI-exposed oocytes and embryos resulted in blastocysts with altered DNA methylation profiles and transcriptomic fingerprints, compared to BASAL-exposed counterparts. Differences in gene expression and methylation were more pronounced after exposure during culture compared to maturation suggesting that zygotes are more susceptible to an adverse environment. Main gene networks affected were related to lipid and carbohydrate metabolism, cell death, immune response and metabolic disorders. This may offer clues regarding the high rate of embryonic loss and metabolic diseases during later stages of life observed in offspring from mothers displaying lipolytic disorders. Two experiments were set up to characterize the epigenomic profile of the resultant day 7.5 blastocysts. In the first (in vitro maturation or IVM) experiment, the effect of elevated NEFA exposure during oocyte maturation (24 h) on DNA methylation profiles was evaluated by exposing oocytes to the BASAL or HIGH COMBI conditions. In the second (in vitro culture or IVC) experiment, the effect of elevated NEFA exposure during embryo culture (6.5 days) on DNA methylation marks was evaluated by exposing embryos to the BASAL or HIGH COMBI conditions. A total of 1039 and 1412 oocytes were used in the IVM and IVC experiment, respectively, equally distributed between treatments in 4 replicates. Resultant day 7.5 blastocysts were snap frozen for subsequent DNA methylation analysis (80 blastocysts in each experiments, equally collected between treatments in 4 replicates).
2016-06-28 | E-GEOD-83766 | biostudies-arrayexpress
Project description:Metabolic stress associated with negative energy balance in high producing dairy cattle and obesity in women is a risk factor for decreased fertility. Non-esterified fatty acids (NEFA) are involved in this pathogenesis as they jeopardize oocyte and embryo development. Growing evidence indicates that maternal metabolic disorders can disturb epigenetic programming, and more specifically DNA methylation, in the offspring. Final oocyte maturation and early embryo development coincide with specific methylation changes and both time periods are sensitive to adverse environments. Therefore, we investigated whether elevated NEFA concentrations affect the establishment and maintenance of DNA methylation patterns in oocytes and embryos and subsequently alter transcriptomic profiles and developmental competence of the resultant blastocysts. To do this, bovine oocytes and embryos were exposed to different NEFA concentrations in two separate experiments. In the first experiment, oocytes were matured in vitro for 24 hours in medium containing: 1) physiological (âBASALâ) concentrations of oleic (OA), palmitic (PA) and stearic (SA) or 2) elevated (pathophysiological or âHIGH COMBIâ) concentrations of OA, PA and SA. In the second experiment, zygotes were cultivated in vitro for 6.5 days under BASAL or HIGH COMBI conditions. The developmental competence was evaluated by assessing cleavage and blastocyst rate. Overall gene expression and DNA methylation of resultant blastocysts were analyzed using microarray techniques. Data regarding DNA methylation were re-evaluated by pyrosequencing. HIGH COMBI-exposed oocytes and embryos displayed a lower competence to develop into blastocysts compared to their BASAL-exposed counterparts (19.3 % compared to 23.2 % and 18.2 % compared to 25.3 %, respectively) (P < 0.05). HIGH COMBI-exposed oocytes and embryos resulted in blastocysts with altered DNA methylation profiles and transcriptomic fingerprints, compared to BASAL-exposed counterparts. Differences in gene expression and methylation were more pronounced after exposure during culture compared to maturation suggesting that zygotes are more susceptible to an adverse environment. Main gene networks affected were related to lipid and carbohydrate metabolism, cell death, immune response and metabolic disorders. This may offer clues regarding the high rate of embryonic loss and metabolic diseases during later stages of life observed in offspring from mothers displaying lipolytic disorders. The effect of elevated NEFA exposure during embryo culture (6.5 days) on gene expression was evaluated by exposing embryos to the BASAL or HIGH COMBI conditions. A total of 1412 oocytes were used, equally distributed between treatments in 4 replicates. Resultant day 7.5 blastocysts were snap frozen for subsequent transcriptome analysis (80 blastocysts in each experiments, equally collected between treatments in 4 replicates).
2016-06-28 | E-GEOD-83767 | biostudies-arrayexpress
Project description:Metabolic stress associated with negative energy balance in high producing dairy cattle and obesity in women is a risk factor for decreased fertility. Non-esterified fatty acids (NEFA) are involved in this pathogenesis as they jeopardize oocyte and embryo development. Growing evidence indicates that maternal metabolic disorders can disturb epigenetic programming, and more specifically DNA methylation, in the offspring. Final oocyte maturation and early embryo development coincide with specific methylation changes and both time periods are sensitive to adverse environments. Therefore, we investigated whether elevated NEFA concentrations affect the establishment and maintenance of DNA methylation patterns in oocytes and embryos and subsequently alter transcriptomic profiles and developmental competence of the resultant blastocysts. To do this, bovine oocytes and embryos were exposed to different NEFA concentrations in two separate experiments. In the first experiment, oocytes were matured in vitro for 24 hours in medium containing: 1) physiological (“BASAL”) concentrations of oleic (OA), palmitic (PA) and stearic (SA) or 2) elevated (pathophysiological or “HIGH COMBI”) concentrations of OA, PA and SA. In the second experiment, zygotes were cultivated in vitro for 6.5 days under BASAL or HIGH COMBI conditions. The developmental competence was evaluated by assessing cleavage and blastocyst rate. Overall gene expression and DNA methylation of resultant blastocysts were analyzed using microarray techniques. Data regarding DNA methylation were re-evaluated by pyrosequencing. HIGH COMBI-exposed oocytes and embryos displayed a lower competence to develop into blastocysts compared to their BASAL-exposed counterparts (19.3 % compared to 23.2 % and 18.2 % compared to 25.3 %, respectively) (P < 0.05). HIGH COMBI-exposed oocytes and embryos resulted in blastocysts with altered DNA methylation profiles and transcriptomic fingerprints, compared to BASAL-exposed counterparts. Differences in gene expression and methylation were more pronounced after exposure during culture compared to maturation suggesting that zygotes are more susceptible to an adverse environment. Main gene networks affected were related to lipid and carbohydrate metabolism, cell death, immune response and metabolic disorders. This may offer clues regarding the high rate of embryonic loss and metabolic diseases during later stages of life observed in offspring from mothers displaying lipolytic disorders.
2016-06-28 | GSE83767 | GEO
Project description:Metabolic stress associated with negative energy balance in high producing dairy cattle and obesity in women is a risk factor for decreased fertility. Non-esterified fatty acids (NEFA) are involved in this pathogenesis as they jeopardize oocyte and embryo development. Growing evidence indicates that maternal metabolic disorders can disturb epigenetic programming, and more specifically DNA methylation, in the offspring. Final oocyte maturation and early embryo development coincide with specific methylation changes and both time periods are sensitive to adverse environments. Therefore, we investigated whether elevated NEFA concentrations affect the establishment and maintenance of DNA methylation patterns in oocytes and embryos and subsequently alter transcriptomic profiles and developmental competence of the resultant blastocysts. To do this, bovine oocytes and embryos were exposed to different NEFA concentrations in two separate experiments. In the first experiment, oocytes were matured in vitro for 24 hours in medium containing: 1) physiological (“BASAL”) concentrations of oleic (OA), palmitic (PA) and stearic (SA) or 2) elevated (pathophysiological or “HIGH COMBI”) concentrations of OA, PA and SA. In the second experiment, zygotes were cultivated in vitro for 6.5 days under BASAL or HIGH COMBI conditions. The developmental competence was evaluated by assessing cleavage and blastocyst rate. Overall gene expression and DNA methylation of resultant blastocysts were analyzed using microarray techniques. Data regarding DNA methylation were re-evaluated by pyrosequencing. HIGH COMBI-exposed oocytes and embryos displayed a lower competence to develop into blastocysts compared to their BASAL-exposed counterparts (19.3 % compared to 23.2 % and 18.2 % compared to 25.3 %, respectively) (P < 0.05). HIGH COMBI-exposed oocytes and embryos resulted in blastocysts with altered DNA methylation profiles and transcriptomic fingerprints, compared to BASAL-exposed counterparts. Differences in gene expression and methylation were more pronounced after exposure during culture compared to maturation suggesting that zygotes are more susceptible to an adverse environment. Main gene networks affected were related to lipid and carbohydrate metabolism, cell death, immune response and metabolic disorders. This may offer clues regarding the high rate of embryonic loss and metabolic diseases during later stages of life observed in offspring from mothers displaying lipolytic disorders.
2016-06-28 | GSE83766 | GEO
Project description:ObjectiveIn this 7-day pilot study we randomized healthy, normal-weight men and women to either a dietary intervention with methionine and cysteine restriction enriched in PUFA (Met/Cyslow?+?PUFA, n?=?7) or with high contents of methionine, cysteine and SFA (Met/Cyshigh?+?SFA, n?=?7). The objective was to describe the short-term responses in oral glucose tolerance, amino acid profile, total fatty acid profile, pyruvate and lactate following a Met/Cyslow?+?PUFA diet vs. Met/Cyshigh?+?SFA.ResultsThe diet groups consisted of five women and two men, aged 20-38 years. After the 7-d intervention median pre- and post-oral glucose tolerance test (OGTT) glucose concentrations were 5 mmol/L and 4 mmol/L respectively in the Met/Cyslow?+?PUFA group. In the Met/Cyshigh?+?SFA group, median pre- and post-OGTT glucose concentrations were 4.8 mmol/L and 4.65 mmol/L after the 7-d intervention. The responses in the amino acid profiles were similar in both groups during the intervention with the exception of serine. Fatty acids decreased from baseline to day 7 in both groups. Plasma lactate and pyruvate were similar for both groups with an increase to day 3 before approaching baseline values at day 7.Trial registrationClinicalTrials.gov: NCT02647970, registration date: January 6th 2016.
| S-EPMC7852127 | biostudies-literature
Project description:ObjectiveObesity and dysmetabolism are major risk factors for atrial fibrillation (AF). Expansion of fat depots is associated with increased circulating total non-esterified fatty acids (NEFAs), elevated levels of which are associated with incident AF. We undertook comprehensive serum measurement of individual NEFA to identify specific associations with new-onset AF late in life.MethodsThe present study focused on participants with available serum and free of AF selected from the Cardiovascular Health Study, a community-based longitudinal investigation of older US adults. Thirty-five individual NEFAs were measured by gas chromatography. Cox regression was used to evaluate the association of individual NEFAs with incident AF.ResultsThe study sample included 1872 participants (age 77.7±4.4). During median follow-up of 11.3 years, 715 cases of incident AF occurred. After concurrent adjustment of all NEFAs and full adjustment for potential confounders, higher serum concentration of nervonic acid (24:1 n-9), a long-chain monounsaturated fatty acid, was associated with higher risk of AF (HR per SD: 1.18, 95% CI 1.08 to 1.29; p<0.001). Conversely, higher serum concentration of gamma-linolenic acid (GLA) (18:3 n-6), a polyunsaturated n-6 fatty acid, was associated with lower risk of AF (HR per SD: 0.81, 95% CI 0.71 to 0.94; p=0.004). None of the remaining NEFAs was significantly associated with AF.ConclusionsAmong older adults, serum levels of non-esterified nervonic acid were positively associated, while serum levels of non-esterified GLA were inversely associated, with incident AF. If confirmed, these results could offer new strategies for AF prevention and early intervention in this segment of the population at highest risk.
| S-EPMC8607526 | biostudies-literature
Project description:Short-term exposure of isolated rat hepatocytes to short- and medium-chain fatty acids led to an activation of acetyl-CoA carboxylase as measured in digitonin-permeabilized hepatocytes. Up to a certain concentration, typical for each of the fatty acids used, fatty acid-dependent activation of acetyl-CoA carboxylase coincided with an increase in the rate of fatty acid synthesis in intact hepatocytes, as determined by the incorporation of 3H from 3H2O water into fatty acids. At higher concentrations loss of stimulation of fatty acid synthesis occurred, but not the enhancement of carboxylase activity. With the fatty acids tested (C8:0-C14:0), the peak in fatty acid synthesis coincided with a peak in the level of malonyl-CoA. The onset of the stimulation of carboxylase activity coincided with the start of the peak in both fatty acid synthesis and malonyl-CoA. The longer the chain length of the fatty acid added, the lower the concentration at which the rate of fatty acid synthesis and the level of malonyl-CoA reached a peak and carboxylase activity started to become elevated. In cell suspensions incubated with increasing concentrations of fatty acids, accumulation of lactate decreased progressively. The latter observation, in combination with the fact that the activity of acetyl-CoA carboxylase is not always related to the rate of fatty acid biosynthesis, suggests that under these conditions not the activity of the carboxylase but the flux through the glycolytic sequence determines, at least in part, the rate of fatty acid synthesis de novo.
| S-EPMC1137201 | biostudies-other
Project description:Maternal obesity and gestational diabetes mellitus (GDM) are associated with adverse intrauterine environments that are high in circulating nutrients. These adverse environments facilitate impairments in placental mitochondrial function and nutrient processing that ultimately leads to an increased risk of the exposed offspring developing non-communicable cardiometabolic health disorders (e.g. obesity, type 2 diabetes, metabolic syndrome). Analysis of fasting serum lipid levels in the third trimester has highlighted that Palmitate (PA) and oleate (OA) are the most abundance non-esterified fatty acids (NEFAs) in circulation. More importantly, these important NEFAs are elevated in both obese and GDM pregnancies. As PA and OA are the most abundant NEFAs in the typical “Westernized Diet” they elevated levels in obese and GDM pregnancies may highlight increased maternal consumption of these fats and could be a link between poor diet and abberant placental function. However, the independent and combined impacts of dietary PA and OA on mitochondrial function and nutrient processing in placental trophoblast cells remains poorly defined. Thus, in this study we sought to utilize a multi-omics approach (combining transcriptomics with untargeted metabolomics and lipidomics) to elucidate the underlying impacts of elevated NEFA levels on BeWo placental trophoblast cells. We highlighted a significant enrichment in the Wikipathways Fatty Acid Biosynthesis Pathway in BeWo cytotrophoblast cells treated with a combination of PA and OA (P/O; 50 µM each). Further, we identified differential expression of genes involved in lipid processing (e.g. ACADVL, ACACB, ACSL5, CREB3L3, PLIN2, and SCD) in BeWo cytotrophoblast cells treated with dietary NEFA species. Overall, these data highlighted that alterations in lipid processing, storage, and oxidation are implicated in the development of placental dysfunction in response to elevated lipid levels.
2023-08-30 | GSE197385 | GEO