Omega-3 long-chain polyunsaturated fatty acids (LCPUFA) have been shown to inhibit lipogenesis an... more Omega-3 long-chain polyunsaturated fatty acids (LCPUFA) have been shown to inhibit lipogenesis and adipogenesis in adult rats. Their possible early life effects on offspring fat deposition, however, remain to be established. To investigate this, female Wistar rats (n = 6–9 per group) were fed either a 9:1 ratio of linoleic acid (LA) to alpha-linolenic acid (ALA) or a lower 1:1.5 ratio during pregnancy and lactation. Each ratio was fed at two total fat levels (18% vs. 36% fat w/w) and offspring were weaned onto standard laboratory chow. Offspring exposed to a 36% fat diet, irrespective of maternal dietary LA:ALA ratio, were lighter (male, 27 g lighter; female 19 g lighter; p < 0.0001) than those exposed to an 18% fat diet between 3 and 8 weeks of age. Offspring exposed to a low LA (18% fat) diet had higher proportions of circulating omega-3 LCPUFA and increased gonadal fat mass at 4 weeks of age (p < 0.05). Reduced Srebf1 mRNA expression of hepatic (p < 0.01), gonadal fat (p...
n-6 Fatty acids have been shown to exert pro-adipogenic effects, whereas n-3 fatty acids work in ... more n-6 Fatty acids have been shown to exert pro-adipogenic effects, whereas n-3 fatty acids work in opposition. Increasing intakes of linoleic acid (LA; n-6) v. α-linolenic acid (ALA; n-3) in Western diets has led to the hypothesis that consumption of this diet during pregnancy may be contributing to adverse offspring health. This study investigated the effects of feeding a maternal dietary LA:ALA ratio similar to that of the Western diet (9:1) compared with a proposed ‘ideal’ ratio (about 1:1·5), at two total fat levels (18 v. 36 % fat, w/w), on growth and lipogenic gene expression in the offspring. Female Wistar rats were assigned to one of the four experimental groups throughout gestation and lactation. Offspring were culled at 1 and 2 weeks of age for sample collection. Offspring of dams consuming a 36 % fat diet were approximately 20 % lighter than those exposed to an 18 % fat diet (P < 0·001). Male, but not female, liver weight at 1 week was approximately 13 % heavier and had ...
Journal of Developmental Origins of Health and Disease
Evidence suggests that sub-optimal maternal nutrition has implications for the developing offspri... more Evidence suggests that sub-optimal maternal nutrition has implications for the developing offspring. We have previously shown that exposure to a low-protein diet during gestation was associated with upregulation of genes associated with cholesterol transport and packaging within the placenta. This study aimed to elucidate the effect of altering maternal dietary linoleic acid (LA; omega-6) to alpha-linolenic acid (ALA; omega-6) ratios as well as total fat content on placental expression of genes associated with cholesterol transport. The potential for maternal body mass index (BMI) to be associated with expression of these genes in human placental samples was also evaluated. Placentas were collected from 24 Wistar rats at 20-day gestation (term = 21–22-day gestation) that had been fed one of four diets containing varying fatty acid compositions during pregnancy, and from 62 women at the time of delivery. Expression of 14 placental genes associated with cholesterol packaging and trans...
A correction to this article has been published and is linked from the HTML and PDF versions of t... more A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Authors: Ronan Muir BSc1, Bethan Clifford BSc1, Sarah McMullen BSc1, PhD, Raheela Khan BSc, PhD2,... more Authors: Ronan Muir BSc1, Bethan Clifford BSc1, Sarah McMullen BSc1, PhD, Raheela Khan BSc, PhD2, Siobhan Quenby BSc3&4, MBBS, Anatoly Shmygol MD, PhD3, Matthew Elmes BSc, PhD1. 1Division of Nutritional Science, School of Bioscience, University of Nottingham, Sutton Bonington Campus, Loughborough, England, United Kingdom, LE12 5RD. 2Graduate School of Medicine, University of Nottingham, Royal Derby Hospital, Uttoxeter Road, Derby, England, United Kingdom, DE22 3DT. 3Division of Translational and Systems Medicine, Warwick Medical School, University of Warwick, Coventry, Warwickshire, England, United Kingdom, CV2 2DX. 4Biomedical Research Unit in Reproductive Health, University Hospital Coventry and Warwickshire, Coventry, Warwickshire, United Kingdom, CV2 2DX. The prevalence of maternal obesity is increasing and is associated with uterine contractile dysfunction and emergency caesarean section. The mechanisms through which maternal obesity causes uterine dysfunction are currently unk...
Maternal obesity is associated with prolonged and dysfunctional labour, potentially through decre... more Maternal obesity is associated with prolonged and dysfunctional labour, potentially through decreased synthesis of prostaglandins that stimulate myometrial contractions. We assessed the impact of maternal obesity on concentrations of precursor fatty acids (FA) for prostaglandin synthesis and whether any changes could be reversed by improved nutrition post-conception. Wistar rats were fed control (CON) or High-Fat, High-cholesterol (HFHC) diets 6 weeks before mating. At conception half the dams switched diets providing 4 dietary groups: (1) CON, (2) HFHC, (3) CON-HFHC or (4) HFHC-CON. During parturition rats were euthanized and FA composition of plasma, liver and uterus determined. Visceral fat was doubled in rats exposed to the HFHC diet prior to and/or during pregnancy compared to CON. HFHC diet increased MUFAs but decreased omega-3 and omega-6 PUFAs in plasma and liver. Uterine omega-3 FA concentrations were halved in HFHC versus CON rats, but all other FAs were similar. Switching...
Maternal obesity is associated with prolonged and dysfunctional labour and emergency caesarean se... more Maternal obesity is associated with prolonged and dysfunctional labour and emergency caesarean section, but the mechanisms are unknown. The present study investigated the effects of an adiposity-inducing high-fat, high-cholesterol (HFHC) diet on uterine contractile-associated protein (CAP) expression and ex vivo uterine contractility in term non-labouring (TNL) and term labouring (TL) rats. Female rats were fed either control chow (CON n=20) or HFHC (n=20) diet 6 weeks before conception and during pregnancy. On gestational day 21 (TNL) or day 22 (TL) CON and HFHC (n=10) rats were killed to determine plasma cholesterol, triacylglycerol and progesterone concentrations and collection of myometrium for contractility studies and expression of CAPs caveolin-1 (Cav-1), connexin-43 (CX-43) and it's phosphorylated form (pCX-43), oxytocin receptor (OXTR) and cyclooxygenase-2 (COX-2). HFHC feeding increased visceral fat (P≤0.001), plasma cholesterol (P≤0.001) and triacylglycerol (P=0.039) ...
The Western diet is typically high in salt and fructose, which have pressor activity. Maternal di... more The Western diet is typically high in salt and fructose, which have pressor activity. Maternal diet can affect offspring blood pressure, but the extent to which maternal intake of excess salt and fructose may influence cardiovascular function of the offspring is unknown. We sought to determine the effect of moderate maternal dietary intake of salt and/or fructose on resting and stimulated cardiovascular function of the adult male and female offspring. Pregnant rats were fed purified diets (±4 % salt) and water (±10 % fructose) before and during gestation and through lactation. Male and female offspring were weaned onto standard laboratory chow. From 9 to 14 weeks of age, cardiovascular parameters (basal, circadian and stimulated) were assessed continuously by radiotelemetry. Maternal salt intake rendered opposite-sex siblings with a 25-mmHg difference in blood pressure as adults; male offspring were hypertensive (15 mmHg mean arterial pressure (MAP)) and female offspring were hypote...
Introduction Obesity is currently the biggest challenge facing maternity services. Over 20% of wo... more Introduction Obesity is currently the biggest challenge facing maternity services. Over 20% of women are obese at conception with rates set to rise by 50% by 2050. Obese women have a substantially higher risk of developing complications during labour compared to women with a healthy BMI, and have a higher risk of emergency caesarean section due to uterine dysfunction and prolonged labour. As contractile associated proteins (CAP’s) are essential to spontaneous contraction of the myometrium, this pilot study investigated the effects of increasing BMI on CAP expression within human term uterine tissue. Methods All participants provided written informed consent to participate in the study Maternal BMI was calculated upon height and weight measurements provided during pregnancy booking at 10-12 weeks. Full thickness myometrial biopsy samples were collected from healthy patients (n=4) with a singleton pregnancy at planned caesarean section (term 37 weeks) following delivery of the baby an...
Advanced maternal age of first time pregnant mothers is associated with prolonged and dysfunction... more Advanced maternal age of first time pregnant mothers is associated with prolonged and dysfunctional labor and significant risk of emergency cesarean section. We investigated the influence of maternal age on myometrial contractility, expression of contractile associated proteins (CAPs), and global gene expression in the parturient uterus. Female Wistar rats either 8 (YOUNG n = 10) or 24 (OLDER n = 10) weeks old were fed laboratory chow, mated, and killed during parturition. Myometrial strips were dissected to determine contractile activity, cholesterol (CHOL) and triglycerides (TAG) content, protein expression of connexin-43 (GJA1), prostaglandin-endoperoxide synthase 2 (PTGS2), and caveolin 1 (CAV-1). Maternal plasma concentrations of prostaglandins PGE2, PGF2α, and progesterone were determined by RIA. Global gene expression in uterine samples was compared using Affymetrix Genechip Gene 2.0 ST arrays and Ingenuity Pathway analysis (IPA). Spontaneous contractility in myometrium exhib...
A maternal low-protein diet (MLP) fed during pregnancy leads to hypertension in adult rat offspri... more A maternal low-protein diet (MLP) fed during pregnancy leads to hypertension in adult rat offspring. Hypertension is a major risk factor for ischaemic heart disease. This study examined the capacity of hearts from MLP-exposed offspring to recover from myocardial ischaemia-reperfusion (IR) and related this to cardiac expression of β-adrenergic receptors (β-AR) and their associated G proteins. Pregnant rats were fed control (CON) or MLP diets (n = 12 each group) throughout pregnancy. When aged 6 months, hearts from offspring underwent Langendorff cannulation to assess contractile function during baseline perfusion, 30 min ischemia and 60 min reperfusion. CON male hearts demonstrated impaired recovery in left ventricular pressure (LVP) and dP/dt(max) (P < 0.01) during reperfusion when compared to MLP male hearts. Maternal diet had no effect on female hearts to recover from IR. MLP males exhibited greater membrane expression of β(2)-AR following reperfusion and urinary excretion of n...
Omega-3 long-chain polyunsaturated fatty acids (LCPUFA) have been shown to inhibit lipogenesis an... more Omega-3 long-chain polyunsaturated fatty acids (LCPUFA) have been shown to inhibit lipogenesis and adipogenesis in adult rats. Their possible early life effects on offspring fat deposition, however, remain to be established. To investigate this, female Wistar rats (n = 6–9 per group) were fed either a 9:1 ratio of linoleic acid (LA) to alpha-linolenic acid (ALA) or a lower 1:1.5 ratio during pregnancy and lactation. Each ratio was fed at two total fat levels (18% vs. 36% fat w/w) and offspring were weaned onto standard laboratory chow. Offspring exposed to a 36% fat diet, irrespective of maternal dietary LA:ALA ratio, were lighter (male, 27 g lighter; female 19 g lighter; p < 0.0001) than those exposed to an 18% fat diet between 3 and 8 weeks of age. Offspring exposed to a low LA (18% fat) diet had higher proportions of circulating omega-3 LCPUFA and increased gonadal fat mass at 4 weeks of age (p < 0.05). Reduced Srebf1 mRNA expression of hepatic (p < 0.01), gonadal fat (p...
n-6 Fatty acids have been shown to exert pro-adipogenic effects, whereas n-3 fatty acids work in ... more n-6 Fatty acids have been shown to exert pro-adipogenic effects, whereas n-3 fatty acids work in opposition. Increasing intakes of linoleic acid (LA; n-6) v. α-linolenic acid (ALA; n-3) in Western diets has led to the hypothesis that consumption of this diet during pregnancy may be contributing to adverse offspring health. This study investigated the effects of feeding a maternal dietary LA:ALA ratio similar to that of the Western diet (9:1) compared with a proposed ‘ideal’ ratio (about 1:1·5), at two total fat levels (18 v. 36 % fat, w/w), on growth and lipogenic gene expression in the offspring. Female Wistar rats were assigned to one of the four experimental groups throughout gestation and lactation. Offspring were culled at 1 and 2 weeks of age for sample collection. Offspring of dams consuming a 36 % fat diet were approximately 20 % lighter than those exposed to an 18 % fat diet (P < 0·001). Male, but not female, liver weight at 1 week was approximately 13 % heavier and had ...
Journal of Developmental Origins of Health and Disease
Evidence suggests that sub-optimal maternal nutrition has implications for the developing offspri... more Evidence suggests that sub-optimal maternal nutrition has implications for the developing offspring. We have previously shown that exposure to a low-protein diet during gestation was associated with upregulation of genes associated with cholesterol transport and packaging within the placenta. This study aimed to elucidate the effect of altering maternal dietary linoleic acid (LA; omega-6) to alpha-linolenic acid (ALA; omega-6) ratios as well as total fat content on placental expression of genes associated with cholesterol transport. The potential for maternal body mass index (BMI) to be associated with expression of these genes in human placental samples was also evaluated. Placentas were collected from 24 Wistar rats at 20-day gestation (term = 21–22-day gestation) that had been fed one of four diets containing varying fatty acid compositions during pregnancy, and from 62 women at the time of delivery. Expression of 14 placental genes associated with cholesterol packaging and trans...
A correction to this article has been published and is linked from the HTML and PDF versions of t... more A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Authors: Ronan Muir BSc1, Bethan Clifford BSc1, Sarah McMullen BSc1, PhD, Raheela Khan BSc, PhD2,... more Authors: Ronan Muir BSc1, Bethan Clifford BSc1, Sarah McMullen BSc1, PhD, Raheela Khan BSc, PhD2, Siobhan Quenby BSc3&4, MBBS, Anatoly Shmygol MD, PhD3, Matthew Elmes BSc, PhD1. 1Division of Nutritional Science, School of Bioscience, University of Nottingham, Sutton Bonington Campus, Loughborough, England, United Kingdom, LE12 5RD. 2Graduate School of Medicine, University of Nottingham, Royal Derby Hospital, Uttoxeter Road, Derby, England, United Kingdom, DE22 3DT. 3Division of Translational and Systems Medicine, Warwick Medical School, University of Warwick, Coventry, Warwickshire, England, United Kingdom, CV2 2DX. 4Biomedical Research Unit in Reproductive Health, University Hospital Coventry and Warwickshire, Coventry, Warwickshire, United Kingdom, CV2 2DX. The prevalence of maternal obesity is increasing and is associated with uterine contractile dysfunction and emergency caesarean section. The mechanisms through which maternal obesity causes uterine dysfunction are currently unk...
Maternal obesity is associated with prolonged and dysfunctional labour, potentially through decre... more Maternal obesity is associated with prolonged and dysfunctional labour, potentially through decreased synthesis of prostaglandins that stimulate myometrial contractions. We assessed the impact of maternal obesity on concentrations of precursor fatty acids (FA) for prostaglandin synthesis and whether any changes could be reversed by improved nutrition post-conception. Wistar rats were fed control (CON) or High-Fat, High-cholesterol (HFHC) diets 6 weeks before mating. At conception half the dams switched diets providing 4 dietary groups: (1) CON, (2) HFHC, (3) CON-HFHC or (4) HFHC-CON. During parturition rats were euthanized and FA composition of plasma, liver and uterus determined. Visceral fat was doubled in rats exposed to the HFHC diet prior to and/or during pregnancy compared to CON. HFHC diet increased MUFAs but decreased omega-3 and omega-6 PUFAs in plasma and liver. Uterine omega-3 FA concentrations were halved in HFHC versus CON rats, but all other FAs were similar. Switching...
Maternal obesity is associated with prolonged and dysfunctional labour and emergency caesarean se... more Maternal obesity is associated with prolonged and dysfunctional labour and emergency caesarean section, but the mechanisms are unknown. The present study investigated the effects of an adiposity-inducing high-fat, high-cholesterol (HFHC) diet on uterine contractile-associated protein (CAP) expression and ex vivo uterine contractility in term non-labouring (TNL) and term labouring (TL) rats. Female rats were fed either control chow (CON n=20) or HFHC (n=20) diet 6 weeks before conception and during pregnancy. On gestational day 21 (TNL) or day 22 (TL) CON and HFHC (n=10) rats were killed to determine plasma cholesterol, triacylglycerol and progesterone concentrations and collection of myometrium for contractility studies and expression of CAPs caveolin-1 (Cav-1), connexin-43 (CX-43) and it's phosphorylated form (pCX-43), oxytocin receptor (OXTR) and cyclooxygenase-2 (COX-2). HFHC feeding increased visceral fat (P≤0.001), plasma cholesterol (P≤0.001) and triacylglycerol (P=0.039) ...
The Western diet is typically high in salt and fructose, which have pressor activity. Maternal di... more The Western diet is typically high in salt and fructose, which have pressor activity. Maternal diet can affect offspring blood pressure, but the extent to which maternal intake of excess salt and fructose may influence cardiovascular function of the offspring is unknown. We sought to determine the effect of moderate maternal dietary intake of salt and/or fructose on resting and stimulated cardiovascular function of the adult male and female offspring. Pregnant rats were fed purified diets (±4 % salt) and water (±10 % fructose) before and during gestation and through lactation. Male and female offspring were weaned onto standard laboratory chow. From 9 to 14 weeks of age, cardiovascular parameters (basal, circadian and stimulated) were assessed continuously by radiotelemetry. Maternal salt intake rendered opposite-sex siblings with a 25-mmHg difference in blood pressure as adults; male offspring were hypertensive (15 mmHg mean arterial pressure (MAP)) and female offspring were hypote...
Introduction Obesity is currently the biggest challenge facing maternity services. Over 20% of wo... more Introduction Obesity is currently the biggest challenge facing maternity services. Over 20% of women are obese at conception with rates set to rise by 50% by 2050. Obese women have a substantially higher risk of developing complications during labour compared to women with a healthy BMI, and have a higher risk of emergency caesarean section due to uterine dysfunction and prolonged labour. As contractile associated proteins (CAP’s) are essential to spontaneous contraction of the myometrium, this pilot study investigated the effects of increasing BMI on CAP expression within human term uterine tissue. Methods All participants provided written informed consent to participate in the study Maternal BMI was calculated upon height and weight measurements provided during pregnancy booking at 10-12 weeks. Full thickness myometrial biopsy samples were collected from healthy patients (n=4) with a singleton pregnancy at planned caesarean section (term 37 weeks) following delivery of the baby an...
Advanced maternal age of first time pregnant mothers is associated with prolonged and dysfunction... more Advanced maternal age of first time pregnant mothers is associated with prolonged and dysfunctional labor and significant risk of emergency cesarean section. We investigated the influence of maternal age on myometrial contractility, expression of contractile associated proteins (CAPs), and global gene expression in the parturient uterus. Female Wistar rats either 8 (YOUNG n = 10) or 24 (OLDER n = 10) weeks old were fed laboratory chow, mated, and killed during parturition. Myometrial strips were dissected to determine contractile activity, cholesterol (CHOL) and triglycerides (TAG) content, protein expression of connexin-43 (GJA1), prostaglandin-endoperoxide synthase 2 (PTGS2), and caveolin 1 (CAV-1). Maternal plasma concentrations of prostaglandins PGE2, PGF2α, and progesterone were determined by RIA. Global gene expression in uterine samples was compared using Affymetrix Genechip Gene 2.0 ST arrays and Ingenuity Pathway analysis (IPA). Spontaneous contractility in myometrium exhib...
A maternal low-protein diet (MLP) fed during pregnancy leads to hypertension in adult rat offspri... more A maternal low-protein diet (MLP) fed during pregnancy leads to hypertension in adult rat offspring. Hypertension is a major risk factor for ischaemic heart disease. This study examined the capacity of hearts from MLP-exposed offspring to recover from myocardial ischaemia-reperfusion (IR) and related this to cardiac expression of β-adrenergic receptors (β-AR) and their associated G proteins. Pregnant rats were fed control (CON) or MLP diets (n = 12 each group) throughout pregnancy. When aged 6 months, hearts from offspring underwent Langendorff cannulation to assess contractile function during baseline perfusion, 30 min ischemia and 60 min reperfusion. CON male hearts demonstrated impaired recovery in left ventricular pressure (LVP) and dP/dt(max) (P < 0.01) during reperfusion when compared to MLP male hearts. Maternal diet had no effect on female hearts to recover from IR. MLP males exhibited greater membrane expression of β(2)-AR following reperfusion and urinary excretion of n...
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