Biology subjects

Sturmey, R. G.

Publications and source records attributed to Sturmey, R. G..

4 recordsLinked to original sources

bioRxiv2026

Glucose-dependent signalling pathways regulate TE differentiation in bovine embryos

Glucose uptake and metabolism increase markedly during the transition from morula to blastocyst. However, the functional roles of glucose during this process in bovine embryos remain incompletely understood. Here, we demonstrate that glucose specifically modulates trophectoderm (TE) differentiation without affecting the inner cell mass (ICM), acting through Hippo signalling via the hexosamine biosynthetic pathway (HBP) and the pentose phosphate pathway (PPP) rather than glycolysis. Consistently, scRNA-seq analysis reveals that unlike glycolysis-related genes, which show only stage-specific changes, HBP- and PPP-related genes exhibit significant differential expression between the TE and ICM lineages. Furthermore, we found that glucose deprivation does not impair pyruvate uptake or intracellular pyruvate levels in blastocysts, yet it significantly depletes the terminal metabolites of the HBP and PPP. Together, these findings reveal that glucose-dependent regulation of TE differentiation is conserved in bovine embryos.

developmental biology↗

bioRxiv2025

JAK and MEK Pathways as Therapeutic Targets for Saphenous Vein Smooth Muscle Cell Dysfunction in Type 2 Diabetes via Regulation of Mitochondrial Activity

AimsGlucose-driven mitochondrial dysfunction has been proposed to promote vascular cell proliferation and migration events responsible for saphenous vein graft failure (VGF) following bypass surgery. However, it is unclear how type 2 diabetes mellitus (T2DM) impacts mitochondrial function in human saphenous vein smooth muscle cells (HSVSMCs) responsible for the maladaptive remodelling responsible for VGF. Therefore, identifying and targeting the signalling pathways involved could offer new therapeutic options to limit VGF. Our aim was to identify signalling pathways that mediate any mitochondrial dysfunction in HSVSMCs in vitro and assess the impact of T2DM. Methods and resultsHSVSMCs explanted from surplus HSV tissues from consenting T2DM and non-diabetic patients undergoing coronary artery bypass graft surgery were treated with known activators and inhibitors of the JAK/STAT and MAPK/ERK pathways. Following this, real-time oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) measures of mitochondrial function were then determined. Our findings revealed that both IL-6/sIL-6R trans-signalling complexes and PDGF-BB significantly increased OCR in HSVSMCs from T2DM patients but not non-diabetic controls. Meanwhile, only PDGF-BB increased ECAR in HSVSMCs from T2DM patients but not non-diabetic controls. The observed increases in OCR and ECAR were abolished by JAK1/2-selective inhibitor ruxolitinib. Furthermore, thrombin caused a significant increase in OCR specifically in HSVSMCs from T2DM patients, and this was abolished by MEK1/2-selective inhibitor trametinib. Both ruxolitinib and trametinib significantly reduced basal OCR and ECAR in HSVSMCs from both T2DM and non-diabetic patients. ConclusionTogether, these findings demonstrate a JAK/STAT- and MAPK/ERK-mediated regulation of mitochondrial function in HSVSMCs. As such, they represent potential targets for regulation of HSVSMC function that can be explored for drug development to limit saphenous VGF in T2DM.

cell biology↗

bioRxiv2025

Oocyte exposure to low levels of triclosan has a significant impact on subsequent embryo physiology.

Triclosan (TCS) is an anti-microbial agent in a wide range of health care products. It has been found in various human bodily fluids and is a potential reproductive toxicant. However, the effect of TCS on early embryo development in mammalian species is limited. We therefore asked whether exposure to TCS affects mammalian cumulus-oocyte-complexes (COCs), and if so, whether the effects persist into the early embryo. COCs, isolated from abattoir-derived bovine ovaries were exposed to two environmentally relevant doses of TCS (1 nM and 10 nM) during in vitrao maturation. When exposed to 1 nM TCS during in vitro maturation, progesterone release from bovine oocytes was elevated. Furthermore, altered pyruvate metabolism and mitochondrial dysfunction also observed; specifically, O2 consumption coupled to ATP production was significantly decreased in COCs after acute exposure of TCS prior to maturation, whereas proton leak from the respiratory chain was increased. Subsequently, TCS-exposed COCs were fertilised. Fewer oocytes were able to develop to blastocyst when exposed to 1 nM TCS during maturation compared to the Control group (12.22{+/-}% vs 29.11{+/-}% n=5; p=0.02) and those that did reach the blastocyst displayed impaired glycolytic and amino acid metabolic activity. These findings indicate for the first time that oocytes exposed to TCS during the final stages of maturation give rise to embryos with impaired mitochondria function, altered steroidogenesis and disrupted metabolic activity.

developmental biology↗

bioRxiv2019

Application of extracellular flux analysis for determining mitochondrial function in mammalian oocytes and early embryos

1.BackgroundMitochondria provide the major source of ATP for mammalian oocyte maturation and early embryo development. Oxygen Consumption Rate (OCR) is an established measure of mitochondrial function. OCR by mammalian oocytes and embryos has generally been restricted to overall uptake and detailed understanding of the components of OCR dedicated to specific molecular events remains lacking.\n\nResultsHere, extracellular flux analysis (EFA) was applied to small groups of bovine, equine, mouse and human oocytes and bovine early embryos to measure OCR. Using EFA, we report the changes in mitochondrial activity during the processes of oocyte maturation, fertilization, and pre-implantation development to blastocyst stage in response to physiological demands in mammalian embryos. Crucially, we describe the real time partitioning of overall OCR to spare capacity, proton leak, non-mitochondrial and coupled respiration - showing that while there are alterations in activity over the course of development to respond to physiological demand, the overall efficiency is unchanged.\n\nConclusionEFA is shown to be able to measure mitochondrial function in small groups of mammalian oocytes and embryos in a manner which is robust, rapid and easy to use. EFA is non-invasive and allows real-time determination of the impact of compounds on OCR, facilitating an assessment of the parameters of mitochondrial activity. This provides proof-of-concept for EFA as an accessible system with which to study oocyte and embryo metabolism.

developmental biology↗