ORCID Profile
0000-0003-0135-329X
Current Organisation
Deakin University
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Publisher: Wiley
Date: 12-09-2023
Publisher: Cold Spring Harbor Laboratory
Date: 28-02-2023
DOI: 10.1101/2023.02.27.530361
Abstract: Sex differences in microRNA (miRNA) expression profiles have been found across multiple tissues. Skeletal muscle is one of the top tissues that underpin sex-based differences, yet there is limited research into whether there are sex differences in miRNA expression in skeletal muscle. Further, there is limited literature investigating potential differences between males and females in skeletal muscle miRNA expression following exercise, a well-known modulator of miRNA expression. Therefore, the aim of this study was to investigate the effect of sex on miRNA expression in skeletal muscle at baseline and after an acute bout of exercise. MiRNAs were measured using Taqman®miRNA arrays in skeletal muscle of 42 healthy participants from the GeneSMART study (24 males and 20 females aged 18-45 yrs). Differentially expressed miRNAs were identified using mixed linear models adjusted for age. Experimentally validated miRNA gene targets enriched in skeletal muscle were identified in-silico. Over representation analysis was conducted to identify enriched pathways. TransmiR V.2 was used to identify transcription factor (TF)-miR regulatory networks using CHIP-derived data. We further profiled the effects of two sex-biased miRNAs overexpressed in human primary muscle cells lines derived from male and female donors to understand the transcriptome targeted by these miRNAs and investigate and potential sex-specific effects. A total of 80 miRNAs were differentially expressed in skeletal muscle between the sexes, with 61 miRNAs responding differently to the exercise between the sexes. Sex-biased miRNA gene targets were enriched for muscle-related processes including proliferation and differentiation of the muscle cells and numerous metabolic pathways, suggesting that miRNAs are playing a role in programming sex differences in skeletal muscle. Over-expression of sex-biased miRNAs miRNA-30a and miRNA-30c resulted in profound changes to gene expression profiles that were partly specific to the sex of the cell donor in human primary skeletal muscle cells. We found sex-differences in the expression profile of skeletal muscle miRNAs at baseline and in response to exercise. These miRNAs target regulatory pathways essential to skeletal muscle development and metabolism, suggesting that miRNAs play a profound but highly complex role in programming sex-differences in the skeletal muscle phenotype.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-01-2022
Publisher: Informa UK Limited
Date: 30-12-2021
DOI: 10.1080/17461391.2021.2011426
Abstract: Previous small-scale studies have shown an association between the
Publisher: Society for Transparency, Openness, and Replication in Kinesiology
Date: 02-06-2022
DOI: 10.51224/SRXIV.158
Publisher: Springer Science and Business Media LLC
Date: 16-10-2018
DOI: 10.1007/S00421-018-4010-0
Abstract: A common null polymorphism (rs1815739 R577X) in the gene that codes for α-actinin-3 (ACTN3) has been related to different aspects of exercise performance. In iduals who are homozygous for the X allele are unable to express the α-actinin-3 protein in the muscle as opposed to those with the RX or RR genotype. α-actinin-3 deficiency in the muscle does not result in any disease. However, the different ACTN3 genotypes can modify the functioning of skeletal muscle during exercise through structural, metabolic or signaling changes, as shown in both humans and in the mouse model. Specifically, the ACTN3 RR genotype might favor the ability to generate powerful and forceful muscle contractions. Leading to an overall advantage of the RR genotype for enhanced performance in some speed and power-oriented sports. In addition, RR genotype might also favor the ability to withstand exercise-induced muscle damage, while the beneficial influence of the XX genotype on aerobic exercise performance needs to be validated in human studies. More information is required to unveil the association of ACTN3 genotype with trainability and injury risk during acute or chronic exercise.
Publisher: Springer Science and Business Media LLC
Date: 16-04-2019
Publisher: American Physiological Society
Date: 11-2018
DOI: 10.1152/AJPREGU.00096.2018
Abstract: It remains unclear whether high-intensity interval exercise (HIIE) elicits distinct molecular responses to traditional endurance exercise relative to the total work performed. We aimed to investigate the influence of exercise intensity on acute perturbations to skeletal muscle mitochondrial function (respiration and reactive oxygen species) and metabolic and redox signaling responses. In a randomized, repeated measures crossover design, eight recreationally active in iduals (24 ± 5 yr V̇o 2peak : 48 ± 11 ml·kg −1 ·min −1 ) undertook continuous moderate-intensity [CMIE: 30 min, 50% peak power output (PPO)], high-intensity interval (HIIE: 5 × 4 min, 75% PPO, work matched to CMIE), and low-volume sprint interval (SIE: 4 × 30 s) exercise, ≥7 days apart. Each session included muscle biopsies at baseline, immediately, and 3 h postexercise for high-resolution mitochondrial respirometry ( Jo 2 ) and H 2 O 2 emission ( Jh 2 o 2 ) and gene and protein expression analysis. Immediately postexercise and irrespective of protocol, Jo 2 increased during complex I + II leak/state 4 respiration but Jh 2 o 2 decreased ( P 0.05). AMP-activated protein kinase and acetyl co-A carboxylase phosphorylation increased ~1.5 and 2.5-fold respectively, while thioredoxin-reductase-1 protein abundance was ~35% lower after CMIE vs. SIE ( P 0.05). At 3 h postexercise, regardless of protocol, Jo 2 was lower during both ADP-stimulated state 3 OXPHOS and uncoupled respiration ( P 0.05) but Jh 2 o 2 trended higher ( P 0.08) and PPARGC1A mRNA increased ~13-fold, and peroxiredoxin-1 protein decreased ~35%. In conclusion, intermittent exercise performed at high intensities has similar dynamic effects on muscle mitochondrial function compared with endurance exercise, irrespective of whether total workload is matched. This suggests exercise prescription can accommodate in idual preferences while generating comparable molecular signals known to promote beneficial metabolic adaptations.
Publisher: Bioscientifica
Date: 04-2020
DOI: 10.1530/EC-19-0551
Abstract: Mechanisms of insulin resistance in polycystic ovary syndrome (PCOS) remain ill defined, contributing to sub-optimal therapies. Recognising skeletal muscle plays a key role in glucose homeostasis we investigated early insulin signalling, its association with aberrant transforming growth factor β (TGFβ)-regulated tissue fibrosis. We also explored the impact of aerobic exercise on these molecular pathways. A secondary analysis from a cross-sectional study was undertaken in women with ( n = 30) or without ( n = 29) PCOS across lean and overweight BMIs. A subset of participants with ( n = 8) or without ( n = 8) PCOS who were overweight completed 12 weeks of aerobic exercise training. Muscle was s led before and 30 min into a euglycaemic-hyperinsulinaemic cl pre and post training. We found reduced signalling in PCOS of mechanistic target of rapamycin (mTOR). Exercise training augmented but did not completely rescue this signalling defect in women with PCOS. Genes in the TGFβ signalling network were upregulated in skeletal muscle in the overweight women with PCOS but were unresponsive to exercise training except for genes encoding LOX, collagen 1 and 3. We provide new insights into defects in early insulin signalling, tissue fibrosis, and hyperandrogenism in PCOS-specific insulin resistance in lean and overweight women. PCOS-specific insulin signalling defects were isolated to mTOR, while gene expression implicated TGFβ ligand regulating a fibrosis in the PCOS-obesity synergy in insulin resistance and altered responses to exercise. Interestingly, there was little evidence for hyperandrogenism as a mechanism for insulin resistance.
Publisher: Cold Spring Harbor Laboratory
Date: 17-03-2021
DOI: 10.1101/2021.03.16.435733
Abstract: Nearly all human complex traits and diseases exhibit some degree of sex differences, with epigenetics being one of the main contributing factors. Various tissues display sex differences in DNA methylation, however this has not yet been explored in skeletal muscle, despite skeletal muscle being among the tissues with the most transcriptomic sex differences. For the first time, we investigated the effect of sex on autosomal DNA methylation in human skeletal muscle across three independent cohorts (Gene SMART, FUSION, and GSE38291) using a meta-analysis approach, totalling 369 human muscle s les (222 males, 147 females), and integrated this with known sex-biased transcriptomics. We found 10,240 differentially methylated regions (DMRs) at FDR 0.005, 94% of which were hypomethylated in males, and gene set enrichment analysis revealed that differentially methylated genes were involved in muscle contraction and substrate metabolism. We then investigated biological factors underlying DNA methylation sex differences and found that circulating hormones were not associated with differential methylation at sex-biased DNA methylation loci, however these sex-specific loci were enriched for binding sites of hormone-related transcription factors (with top TFs including androgen ( AR ), estrogen ( ESR1 ), and glucocorticoid ( NR3C1 ) receptors). Fibre type proportions were associated with differential methylation across the genome, as well as across 16 % of sex-biased DNA methylation loci (FDR 0.005). Integration of DNA methylomic results with transcriptomic data from the GTEx database and the FUSION cohort revealed 326 autosomal genes that display sex differences at both the epigenome and transcriptome levels. Importantly, transcriptional sex-biased genes were overrepresented among epigenetic sex-biased genes (p-value = 4.6e-13), suggesting differential DNA methylation and gene expression between male and female muscle are functionally linked. Finally, we validated expression of three genes with large effect sizes ( FOXO3A, ALDH1A1 , and GGT7 ) in the Gene SMART cohort with qPCR. GGT7 , involved in antioxidant metabolism, displays male-biased expression as well as lower methylation in males across the three cohorts. In conclusion, we uncovered 8,420 genes that exhibit DNA methylation differences between males and females in human skeletal muscle that may modulate mechanisms controlling muscle metabolism and health. The importance of uncovering biological sex differences and their translation to physiology has become increasingly evident. Using a large-scale meta-analysis of three cohorts, we perform the first comparison of genome-wide skeletal muscle DNA methylation between males and females, and identify thousands of genes that display sex-differential methylation. We then explore intrinsic biological factors that may be underlying the DNA methylation sex differences, such as fibre type proportions and sex hormones. Leveraging the GTEx database, we identify hundreds of genes with both sex-differential expression and DNA methylation in skeletal muscle. We further confirm the sex-biased genes with gene expression data from two cohorts included in the methylation meta-analysis. Our study integrates genomewide sex-biased DNA methylation and expression in skeletal muscle, shedding light on distinct sex differences in skeletal muscle.
Publisher: Wiley
Date: 19-06-2018
DOI: 10.1111/CEN.13753
Abstract: Polycystic ovary syndrome (PCOS) affects up to 13% women and is associated with significant complications. The quality of evidence supporting the recommendations on treatment of nonreproductive outcomes in PCOS is unknown. To summarize and appraise the methodological quality of systematic reviews and meta-analyses evaluating pharmacological and surgical treatments for nonreproductive outcomes in PCOS. A literature search from MEDLINE, EMBASE, CINAHL PLUS and PROSPERO was performed from inception until 15th of September 2017. Article selection, data extraction and quality appraisal of included reviews were performed in duplicate. A narrative synthesis of the findings was conducted. This overview included 31 reviews. The quality was low for 7 (23%), moderate for sixteen (52%) and high for 8 reviews (26%). Two reviews assessed psychological outcomes. Metformin improved anthropometric (7 of 10 reviews), metabolic (4 of 14 reviews) and endocrine outcomes (3 of twelve reviews). Thiazolidinediones improved metabolic (2 of 5 reviews) and endocrine outcomes (one of 5 reviews) but worsened weight gain (5 of 5 reviews). Combined oral contraceptive pill (COCP) improved clinical hyperandrogenism (2 of 2 reviews). Statins improved lipid profile (3 of 3 reviews) and testosterone level (2 of 3 reviews). There was no conclusive evidence from included systematic reviews regarding the use of other interventions. There is reliable evidence regarding the use of metformin for anthropometric outcomes and COCPs for hyperandrogenism in women with PCOS but not for other interventions. There is significant gap in knowledge regarding the management of psychological outcomes in women with PCOS which needs further evaluation.
Publisher: Informa UK Limited
Date: 13-05-2019
Publisher: Wiley
Date: 07-12-2021
DOI: 10.1113/JP279499
Abstract: Sex differences in exercise physiology, such as substrate metabolism and skeletal muscle fatigability, stem from inherent biological factors, including endogenous hormones and genetics. Studies investigating exercise physiology frequently include only males or do not take sex differences into consideration. Although there is still an underrepresentation of female participants in exercise research, existing studies have identified sex differences in physiological and molecular responses to exercise training. The observed sex differences in exercise physiology are underpinned by the sex chromosome complement, sex hormones and, on a molecular level, the epigenome and transcriptome. Future research in the field should aim to include both sexes, control for menstrual cycle factors, conduct large‐scale and ethnically erse studies, conduct meta‐analyses to consolidate findings from various studies, leverage unique cohorts (such as post‐menopausal, transgender, and those with sex chromosome abnormalities), as well as integrate tissue and cell‐specific ‐omics data. This knowledge is essential for developing deeper insight into sex‐specific physiological responses to exercise training, thus directing future exercise physiology studies and practical application. image
Publisher: Oxford University Press (OUP)
Date: 04-01-2019
Abstract: Polycystic ovary syndrome (PCOS) is a major contributor to subfertility, diabetes and cardiovascular disease in women. The role of non-pharmacological interventions to prevent these outcomes has been reported in many systematic reviews, but robust conclusions have not been made due to variations in the scope, quality and findings of these reviews. Our aim was to provide an overview of existing evidence on the effects of non-pharmacological interventions in women with PCOS on fertility and non-fertility outcomes by a review of existing systematic reviews. We reviewed systematic reviews of randomized trials that have evaluated the effects of non-pharmacological interventions, such as lifestyle interventions, nutritional supplements or alternative medicine therapies in women with PCOS on fertility, endocrine, glycaemic and weight-related outcomes. We assessed the quality of systematic reviews with the AMSTAR tool, and reported the outcomes with regard to: fertility (live birth, clinical pregnancy, ovulation and menstrual cycle regularization) endocrine outcomes (Ferriman–Gallwey score, free androgen index, free testosterone and total testosterone levels) and glycaemic (fasting blood insulin, fasting blood glucose, homoeostatic model assessment) and weight-related (BMI) outcomes. We assessed the strength of evidence for significant outcomes as per the grading of recommendations assessment, development and evaluation (GRADE) system. We found twelve eligible systematic reviews which included between three (143 women) and 27 randomized trials (2093 women). Four reviews assessed the effects of lifestyle interventions (diet, physical activity and/or behavioural interventions) four evaluated nutritional supplements (one each on n-acetylcysteine, omega-3 fatty acids, inositol and vitamin D) and four studied alternative medical therapies (Chinese herbal medicine and acupuncture). All of the included reviews were of high quality and scored between 8 and 11 with the AMSTAR tool (with a maximum score of 11). Randomized evidence is lacking for live birth rate. N-acetylcysteine, inositol and the addition of alternative medicine to ovulation induction agents show preliminary potential to improve fertility (odds ratios (OR) for clinical pregnancy rate range from 1.99 to 4.83). Lifestyle interventions show benefits in improving hirsutism (mean difference (MD): −1.01 to −1.19). Lifestyle interventions (MD: −1.10 to −2.02), inositol (MD: −2.1) and acupuncture (MD: −1.90 to −3.43) all show some evidence of improvement in glycaemic outcomes and there is some evidence of reduced BMI with lifestyle interventions (MD: −0.15 to −1.12). All of these outcomes scored either low or very low quality of evidence on the GRADE score. Lifestyle interventions in women with PCOS appear to improve glycaemic results, androgenic symptoms and anthropometric outcomes. The role of inositol and N-acetylcysteine in women with PCOS needs further evaluation. Large primary trials on all interventions are needed for an agreed set of core outcomes.
Publisher: Wiley
Date: 12-02-2018
DOI: 10.1111/APHA.13039
Abstract: The aim of this study was to investigate the effects of 4 consecutive simulated night shifts on glucose homeostasis, mitochondrial function and central and peripheral rhythmicities compared with a simulated day shift schedule. Seventeen healthy adults (8M:9F) matched for sleep, physical activity and dietary/fat intake participated in this study (night shift work n = 9 day shift work n = 8). Glucose tolerance and insulin sensitivity before and after 4 nights of shift work were measured by an intravenous glucose tolerance test and a hyperinsulinaemic euglycaemic cl respectively. Muscles biopsies were obtained to determine insulin signalling and mitochondrial function. Central and peripheral rhythmicities were assessed by measuring salivary melatonin and expression of circadian genes from hair s les respectively. Fasting plasma glucose increased (4.4 ± 0.1 vs. 4.6 ± 0.1 mmol L Only 4 days of simulated night shift work in healthy adults is sufficient to reduce insulin sensitivity which would be expected to increase the risk of T2D.
Publisher: Cold Spring Harbor Laboratory
Date: 24-06-2023
DOI: 10.1101/2023.06.22.545905
Abstract: The inter-session reliability of a wide range of measures used to characterize the aging neuromuscular system is unknown, particularly in females. The aim of this study was to determine the inter-session reliability of quadriceps neuromuscular function assessed via maximal voluntary and evoked force and electromyography responses in healthy young and older females. Twenty-six females aged 19 – 74 years completed two identical testing sessions 9 ± 7 days apart. Quadriceps neuromuscular function measurements included isometric maximal voluntary force (MVC), high and low frequency twitch force, voluntary and evoked electromyography (EMG) in superficial quadriceps (RMS, M-wave and H-reflex), and maximal torque (T0), velocity (V0) and power (P MAX ) derived from torque-velocity and power-velocity relationships. Intra-class correlation coefficients (ICC), coefficients of variation (CoV) and Bland-Altman plots were used to assess inter-session reliability. The effect of participant age on inter-session reliability was assessed by linear regression. Excellent reliability (ICC 0.8) was shown for all voluntary and evoked mechanical outcomes and systematic bias was essentially absent. Similarly, all vastus lateralis EMG outcomes showed excellent reliability (ICC 0.8) with CoVs 12%, which were better than vastus medialis and rectus femoris outcomes. Participant age was not associated with inter-session reliability (P 0.05). Excellent reliability of voluntary and evoked force and vastus lateralis EMG outcomes measured in healthy females can be attained in one testing session, irrespective of age, increasing feasibility for future research. The random error should however be considered when quantifying age-related differences and/or adaptation to exercise in female neuromuscular function. The test-retest reliability of a erse range of measures used to quantify neuromuscular function were assessed in younger and older females for the first time. We show that reliable measures of maximal voluntary and evoked quadriceps force and electromyography outcomes can be obtained in one testing session, irrespective of participant age. Thus, neuromuscular function can be accurately assessed across the female lifespan with minimal inconvenience imposed on participants, increasing feasibility for future research.
Publisher: Wiley
Date: 21-11-2017
DOI: 10.1113/JP275133
Publisher: Wiley
Date: 29-07-2021
DOI: 10.14814/PHY2.14962
Publisher: Georg Thieme Verlag KG
Date: 21-07-2021
DOI: 10.1055/A-1198-5496
Abstract: This review summarised robust and consistent genetic variants associated with aerobic-related and resistance-related phenotypes. In total we highlight 12 SNPs and 7 SNPs that are robustly associated with variance in aerobic-related and resistance-related phenotypes respectively. To date, there is very little literature ascribed to understanding the interplay between genes and environmental factors and the development of physiological traits. We discuss future directions, including large-scale exercise studies to elucidate the functional relevance of the discovered genomic markers. This approach will allow more rigour and reproducible research in the field of exercise genomics.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.FERTNSTERT.2017.11.020
Abstract: To examine the role of high-molecular-weight (HMW) adiponectin and its relationship to sympathetic activity in women with polycystic ovary syndrome (PCOS). Cross sectional study using biobanked s les. Not applicable. Premenopausal women with PCOS (n = 46, Rotterdam diagnostic criteria) and without PCOS (n = 22). None. High-molecular-weight adiponectin levels with secondary outcomes of sympathetic activity and leptin levels. The high-molecular-weight adiponectin level was lower in women with PCOS (median 2.2 [interquartile range (IQR)2.3] μg/mL) than in controls (median 3 [IQR2.5] μg/mL) (age and BMI adjusted), and it correlated inversely with the values measured for homeostatic model of assessment of insulin resistance (HOMA-IR), fasting insulin, triglycerides, and free androgen index and positively with sex hormone-binding globulin (SHBG) and high-density lipoprotein cholesterol in all participants and in the PCOS group. In the PCOS group, sympathetic activity (burst frequency) was statistically significantly higher than in controls (median 26 [IQR11] vs. median 22 [IQR14], respectively) and correlated inversely with HMW adiponectin (r = -0.230). The leptin levels were similar between the women with PCOS and controls and did not statistically significantly correlate with HMW adiponectin or sympathetic activity. On multiple regression analysis, burst frequency and SHBG explained 40% of the HMW adiponectin variability (B = -0.7 95% CI -1.2 to -0.2 and B = 0.01 95% CI 0.004-0.01) in PCOS. Alongside insulin resistance, increased sympathetic activity is associated with and may modulate HMW adiponectin levels in women with PCOS.
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.BONE.2019.03.015
Abstract: Osteocalcin (OC) is used as a surrogate marker for bone turnover in clinical settings. As bone mineral density (BMD) is largely heritable, we tested the hypothesis that a) bone-associated genetic variants previously identified in Genome-Wide Association Studies (GWAS) and combined into a genetic risk score (GRS) are associated with a) circulating levels of OC and b) the changes in OC following acute exercise. Total OC (tOC), undercarboxylated OC (ucOC), and carboxylated OC (cOC) were measured in serum of 73 healthy Caucasian males at baseline and after a single bout of high-intensity interval exercise. In addition, genotyping was conducted targeting GWAS variants previously reported to be associated with BMD and then combined into a GRS. Potential associations between the GRS and tOC, ucOC and cOC were tested with linear regressions adjusted for age. At baseline none of the in idual SNPs associated with tOC, ucOC and cOC. However, when combined, a higher GRS was associated with higher tOC (β = 0.193 ng/mL p = 0.037 95% CI = 0.012, 0.361) and cOC (β = 0.188 ng/mL p = 0.04 95% CI = 0.004, 0.433). Following exercise, GRS was associated with ucOC levels, (β = 3.864 ng/mL p-value = 0.008 95% CI = 1.063, 6.664) but not with tOC or cOC. Screening for genetic variations may assist in identifying people at risk for abnormal circulating levels of OC at baseline/rest. Genetic variations in BMD predicted the ucOC response to acute exercise indicating that physiological functional response to exercise may be influenced by bone-related gene variants.
Publisher: American Physiological Society
Date: 08-2020
Publisher: Elsevier BV
Date: 03-2021
Publisher: Impact Journals, LLC
Date: 03-01-2020
Publisher: The Endocrine Society
Date: 07-08-2019
Abstract: Polycystic ovary syndrome (PCOS) is a chronic disease affecting reproductive function and whole-body metabolism. Although the etiology is unclear, emerging evidence indicates that the epigenetics may be a contributing factor. To determine the role of global and genome-wide epigenetic modifications in specific immune cells in PCOS compared with controls and whether these could be related to clinical features of PCOS. Cross-sectional study. Women with (n = 17) or without PCOS (n = 17). Recruited from the general community. Isolated peripheral blood mononuclear cells were analyzed using multicolor flow cytometry methods to determine global DNA methylation levels in a cell-specific fashion. Transcriptomic and genome-wide DNA methylation analyses were performed on T helper cells using RNA sequencing and reduced representation bisulfite sequencing. Women with PCOS had lower global DNA methylation in monocytes (P = 0.006) and in T helper (P = 0.004), T cytotoxic (P = 0.004), and B cells (P = 0.03). Specific genome-wide DNA methylation analysis of T helper cells from women with PCOS identified 5581 differentially methylated CpG sites. Functional gene ontology enrichment analysis showed that genes located at the proximity of differentially methylated CpG sites belong to pathways related to reproductive function and immune cell function. However, these genes were not altered at the transcriptomic level. It was shown that PCOS is associated with global and gene-specific DNA methylation remodeling in a cell type–specific manner. Further investigation is warranted to determine whether epigenetic reprogramming of immune cells is important in determining the different phenotypes of PCOS.
Publisher: Wiley
Date: 18-09-2018
DOI: 10.1111/CEN.13828
Abstract: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting reproductive-aged women with adverse reproductive, metabolic and psychological outcomes. It has a complex pathophysiology and therefore requires a multidiscipline clinical approach. However, there remains limited research synthesizing the broad clinical implications of PCOS which would assist clinicians in the management of PCOS. To summarize and appraise methodological quality of systematic reviews and meta-analyses evaluating complications and comorbidities associated with PCOS. A literature search from MEDLINE, EMBASE, CINAHL PLUS and PROSPERO was performed until 15 September 2017. Article selection, data extraction and quality appraisal of included reviews using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool were performed in duplicate. A narrative synthesis of the findings was conducted. Twenty-three reviews were included. All reviews were of low (n = 2) to moderate quality (n = 21). PCOS was associated with adverse pregnancy outcomes (n = 2), impaired glucose tolerance (n = 6), insulin resistance (n = 6), increased risk of type 2 diabetes (n = 1), cardiovascular disease (n = 10), metabolic syndrome (n = 2), psychological stress (n = 7), endometrial cancer (n = 1) and vitamin D deficiency (n = 1). Obesity exacerbates many of these outcomes. There is a large body of reliable evidence for adverse metabolic outcomes and smaller, but consistent evidence for psychological issues in PCOS. We identified a shortage of systematic reviews regarding pregnancy outcomes of PCOS and significant gaps in knowledge of the association between PCOS and subclinical hyperthyroidism, vitamin D levels and cancers which future studies could aim to address.
Publisher: Wiley
Date: 15-09-2017
DOI: 10.1002/DMRR.2926
Abstract: To investigate the association of adipocytokines and other inflammatory markers with development of GDM. Serum adipocytokines and inflammatory markers were studied at 12 to 15 weeks gestation using biobanked control s les from a randomised trial. Study participants were identified as high risk for GDM using a validated clinical risk prediction tool. Markers were tested using commercial ELISA kits for high molecular weight (HMW) adiponectin, interleukin-6 (IL-6), plasminogen activator inhibitor-1, visfatin, omentin-1, sex-hormone binding globulin, monocyte chemoattractant protein, and asymmetrical dimethylarginine. The association between each biomarker and development of GDM at 24 to 28 weeks was evaluated using multivariable logistic regression analysis adjusted for maternal factors. There were no differences in age, parity, country of birth, smoking, body mass index, or family history of diabetes in women with normal glucose tolerance (n = 78) and women who developed GDM (n = 25). Women with GDM were more likely to have a past history of GDM (P = 0.004). HMW adiponectin (odds ratio OR 0.37 [95% confidence interval 0.19-0.74]), omentin-1 (0.97 [0.94-0.99]), and IL-6 (1.87[1.03-3.37]) were associated with development of GDM, after adjustment for maternal age, body mass index, and past history of GDM. The other markers were not associated with GDM development. Decreased high molecular weight adiponectin and omentin-1 and increased IL-6 may enhance sensitivity of early risk prediction tools for women at high risk of GDM. This may allow early identification and opportunities for prevention of GDM and adverse outcomes. Further research is required in large validation studies to confirm these results.
Publisher: Springer Science and Business Media LLC
Date: 21-02-2023
DOI: 10.1038/S41598-023-29503-1
Abstract: Women with PCOS have substantially greater symptoms of depression and anxiety, and a lower health-related quality of life (HRQoL) compared to women without PCOS. The aim of this study was to determine if high-intensity interval training (HIIT) could provide greater improvements in mental health outcomes than standard moderate-intensity continuous training (MICT). Twenty-nine overweight women with PCOS aged 18–45 years were randomly assigned to 12 weeks of either MICT (60–75% HR peak , N = 15) or HIIT ( 90% HR peak , N = 14). Outcome measures included symptoms of depression, anxiety and stress (DASS-21), general HRQoL (SF-36) and PCOS specific HRQoL (PCOSQ) collected at baseline and post-intervention. Reductions in depression (Δ − 1.7, P = 0.005), anxiety (Δ − 3.4, P 0.001) and stress (Δ − 2.4, P = 0.003) scores were observed in the HIIT group, while MICT only resulted in a reduction in stress scores (Δ − 2.9, P = 0.001). Reductions in anxiety scores were significantly higher in the HIIT group compared to the MICT group (β = − 2.24, P = 0.020). Both HIIT and MICT significantly improved multiple domain scores from the SF-36 and PCOSQ. This study highlights the potential of HIIT for improving mental health and HRQoL in overweight women with PCOS. HIIT may be a viable strategy to reduce symptoms of depression and anxiety in women with PCOS, however, large-scale studies are required to confirm these findings. Trial registration number : ACTRN12615000242527.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.BONE.2019.115085
Abstract: Osteocalcin (OC), an osteoblast-specific secreted protein expressed by mature osteoblasts, is used in clinical practice and in research as a marker of bone turnover. The carboxylated (cOC) and undercarboxylated (ucOC) forms may have a different biological function but age-specific reference ranges for these components are not established. Given the different physiological roles, development of reference ranges may help to identify people at risk for bone disease. Blood was collected in the morning after an overnight fast from 236 adult men (18 to 92 years old) free of diabetes, antiresorptive, warfarin or glucocorticoid use. Serum was analyzed for total osteocalcin (tOC) and the ucOC fraction using the hydroxyapatite binding method. cOC, ucOC/tOC and cOC/tOC ratios were calculated. Reference intervals were established by polynomial quantile regression analysis. The normal ranges for young men (≤30 years) were: tOC 17.9-56.8 ng/mL, ucOC 7.1-22.0 ng/mL, cOC 8.51-40.3 ng/mL (2.5th to 97.5th quantiles). Aging was associated with a "U" shaped pattern for tOC, cOC and ucOC levels. ucOC/tOC ratio was higher, while cOC/tOC ratio was lower in men of advanced age. Age explained ∼31%, while body mass index explained ∼4%, of the variance in the ratios. We have defined normal reference ranges for the OC forms in Australian men and demonstrated that the OC ratios may be better measures, than the absolute values, to identify the age-related changes on OC in men. These ratios may be incorporated into future research and clinical trials, and their associations with prediction of events, such as fracture or diabetes risk, should be determined.
Publisher: Cold Spring Harbor Laboratory
Date: 21-12-2022
DOI: 10.1101/2022.12.20.22283756
Abstract: Cell-free microRNAs (cf-miRNAs) are secreted from cells and transported via the blood to exert their effect on target tissues. Numerous pathophysiological adaptations, including exercise, alter cf-miRNA levels. The aim of the systematic review was to investigate the cf-miRNA response to an acute bout of exercise and to interpret it using a robust correlated and hierarchical effects (CHE) meta-analysis. The systematic review was registered in PROSPERO (CRD42021256303). A CHE meta-analysis was used to compare the changes in cf-miRNA levels and the influence of exercise modality. An exploratory machine-learning-based approach was used to capture influential moderators. Primary studies were retrieved from PubMed and SPORTDiscus (09.03.2022). Relative changes in cf-miRNA expression in response to exercise were computed for each study. The ROBINS-I, GRADE and AMSTAR2 tools were used to assess evidence certainty and risk of bias. Thirty-six studies including an acute exercise intervention in N=880 healthy males and females aged 18-45yrs met the eligibility criteria. Muscle enriched cf-miR-1 (N=320), cf-miR-133a (N=195) and cf-miR-133b (N=132) levels increased 1-2hr (cf-miR1: FC = 2.72, 95% CI= 1.5-4.0 cf-miR133a: FC = 2.10, 95% CI = 1.6-2.6 cf-miR-133b: FC = 2.39, 95% CI = 1.2-3.6) and 24 hr post-exercise (cf-miR1: FC = 2.25, 95% CI= 1.3-3.2 cf-miR133a: FC = 1.81, 95% CI = 1.4-2.2 cf-miR-133b: FC = 1.99, 95% CI = 1.2-2.8). Acute exercise triggers temporal and modality specific responses in cf-miRNAs. levels. Influential moderators included s le size, collection time point, exercise modality, age and the use of various technical quality controls. Exercise acutely alters cell-free miRNA (cf-miRNA) levels in human serum and plasma, but research is poorly reproducible Muscle-enriched cf-miRNA levels robustly increase following an acute bout of exercise, with temporal and modality specific responses The implementation of a CHE model, a novel statistical approach within the miRNA field, allowed to identify key methodological factors moderating cf-miRNA levels. Strict implementation of these factors is warranted to improve rigour and reproducibility in this field.
Publisher: Wiley
Date: 23-04-2022
DOI: 10.1113/JP283102
Publisher: Cold Spring Harbor Laboratory
Date: 23-05-2023
DOI: 10.1101/2023.05.18.23290199
Abstract: Ageing is associated with a loss of skeletal muscle mass and function that negatively impacts the independence and quality of life of older in iduals. Females demonstrate a distinct pattern of muscle ageing compared to males, potentially due to menopause where endogenous sex hormone production declines. This systematic review aims to investigate the current knowledge about the role of oestrogen in female skeletal muscle ageing. A systematic search of MEDLINE complete, Global Health, Embase, PubMed, SPORTDiscus, and CINHAL was conducted. Studies were considered eligible if they compared a state of oestrogen deficiency (e.g. postmenopausal females) or supplementation (e.g. oestrogen replacement therapy) to normal oestrogen conditions (e.g. premenopausal females or no supplementation). Outcome variables of interest included measures of skeletal muscle mass, function, damage/repair, and energy metabolism. Quality assessment was completed with the relevant Johanna Briggs critical appraisal tool, and data were synthesised in a narrative manner. Thirty-two studies were included in the review. Compared to premenopausal females, postmenopausal females display reduced muscle mass and strength, but the effect of menopause on markers of muscle damage and expression of the genes involved in metabolic signalling pathways remains unclear. Some studies suggest a beneficial effect of oestrogen replacement therapy on muscle size and strength, but evidence is largely conflicting and inconclusive, potentially due to large variations in the reporting and status of exposure and outcomes. The findings from this review points toward a potential negative effect of oestrogen deficiency in ageing skeletal muscle, but further mechanistic evidence is needed to clarify its role. The role of oestrogen in female skeletal muscle ageing. ↑ = significant increase, ↓ = significant decrease, ≠ = significantly different, ? = mixed evidence, p .05. ALM: appendicular lean mass AMPK: adenosine monophosphate kinase CSA: cross-sectional area PGC-1α: peroxisome proliferator-activated receptor gamma coactivator 1-alpha. Created with BioRender.com .
Publisher: American Physiological Society
Date: 15-04-2013
DOI: 10.1152/AJPENDO.00568.2012
Abstract: The aim of this research was to examine the impact of the xanthine oxidase (XO) inhibitor allopurinol on the skeletal muscle activation of cell signaling kinases' and adaptations to mitochondrial proteins and antioxidant enzymes following acute endurance exercise and endurance training. Male Sprague-Dawley rats performed either acute exercise (60 min of treadmill running, 27 m/min, 5% incline) or 6 wk of endurance training (5 days/wk) while receiving allopurinol or vehicle. Allopurinol treatment reduced XO activity to 5% of the basal levels ( P 0.05), with skeletal muscle uric acid levels being almost undetectable. Following acute exercise, skeletal muscle oxidized glutathione (GSSG) significantly increased in allopurinol- and vehicle-treated groups despite XO activity and uric acid levels being unaltered by acute exercise ( P 0.05). This suggests that the source of ROS was not from XO. Surprisingly, muscle GSSG levels were significantly increased following allopurinol treatment. Following acute exercise, allopurinol treatment prevented the increase in p38 MAPK and ERK phosphorylation and attenuated the increase in mitochondrial transcription factor A (mtTFA) mRNA ( P 0.05) but had no effect on the increase in peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), nuclear respiratory factor-2, GLUT4, or superoxide dismutase mRNA. Allopurinol also had no impact on the endurance training-induced increases in PGC-1α, mtTFA, and mitochondrial proteins including cytochrome c, citrate synthase, and β-hydroxyacyl-CoA dehydrogenase. In conclusion, although allopurinol inhibits cell signaling pathways in response to acute exercise, the inhibitory effects of allopurinol appear unrelated to exercise-induced ROS production by XO. Allopurinol also has little effect on increases in mitochondrial proteins following endurance training.
Publisher: Wiley
Date: 23-08-2017
Abstract: Maternal vitamin D deficiency has been implicated in adverse pregnancy outcomes. However, the association between vitamin D and inflammation, particularly adipokines, remains unexplored in pregnancy. In 102 overweight or obese pregnant women at high-risk of gestational diabetes mellitus (GDM), we investigated relationships between maternal 25-hydroxyvitamin D (25(OH)D) concentrations at 12-15 wk gestation (baseline) and serum lipids, inflammatory markers, novel adipokines (omentin-1, visfatin, high molecular weight (HMW) adiponectin), and subsequent pregnancy outcomes (GDM, preecl sia, preterm birth [PTB]). After adjustment for maternal factors (age, BMI, parity, ethnicity, and smoking status), baseline 25(OH)D concentrations were inversely associated with total cholesterol and triglycerides, and positively associated with HMW-adiponectin. Higher baseline 25(OH)D concentrations were associated with decreased fasting and 1-h post-OGTT glucose and reduced risk of GDM at 26-28 wk, as well as with longer gestation and reduced risk of PTB upon additional adjustment for caesarean section. Adding HMW-adiponectin to the multivariable models attenuated most associations, and HMW-adiponectin was a significant predictor in the models. Our findings suggest that lower maternal 25(OH)D concentrations in overweight/obese pregnant women at high-risk of GDM are associated with increased cardiometabolic risks during pregnancy and adverse pregnancy outcomes, and that these associations may be mediated by HMW-adiponectin.
Publisher: MDPI AG
Date: 03-10-2019
DOI: 10.3390/JCM8101606
Abstract: Polycystic Ovary Syndrome (PCOS) is a complex condition with mechanisms likely to involve the interaction between genetics and lifestyle. Familial clustering of PCOS symptoms is well documented, providing evidence for a genetic contribution to the condition. This overview aims firstly to systematically summarise the current literature surrounding genetics and PCOS, and secondly, to assess the methodological quality of current systematic reviews and identify limitations. Four databases were searched to identify candidate gene systematic reviews, and quality was assessed with the AMSTAR tool. Genome-wide association studies (GWAS) were identified by a semi structured literature search. Of the candidate gene systematic reviews, 17 were of high to moderate quality and four were of low quality. A total of 19 gene loci have been associated with risk of PCOS in GWAS, and 11 of these have been replicated across two different ancestries. Gene loci were located in the neuroendocrine, metabolic, and reproductive pathways. Overall, the gene loci with the most robust findings were THADA, FSHR, INS-VNTR, and DENND1A, that now require validation. This overview also identified limitations of the current literature and important methodological considerations for future genetic studies. Much work remains to identify causal variants and functional relevance of genes associated with PCOS.
No related grants have been discovered for Danielle Hiam.